This document provides an overview of achieving treatment outcomes for diabetic patients using DPP4 inhibitors. It begins with background on the presenter and discusses prevalence of diabetes worldwide. It then covers updates on diabetes classification, diagnosis, and management approaches from ADA guidelines. It discusses antihyperglycemic therapy and PERKENI guidelines. The document focuses on incretins and DPP-4 inhibition, comparing different DPP4 inhibitors. Studies show vildagliptin provides better 24-hour glucose fluctuation control and reduction in oxidative stress compared to sitagliptin. The conclusion is that vildagliptin may be better than sitagliptin at reducing glycemic variability and its associated complications.
This document provides an overview of a continuing medical education (CME) program on the use of vildagliptin in managing type 2 diabetes mellitus (T2DM). The presentation covers the global burden of diabetes, pathophysiology of T2DM, limitations of current oral therapies, the incretin system, and the mechanisms and effects of DPP-4 inhibitors like vildagliptin. It discusses how vildagliptin improves pancreatic beta cell function and glucose control by prolonging the actions of incretins GLP-1 and GIP. The presentation also highlights the differences between incretin mimetics and DPP-4 inhibitors.
An Update On Dpp 4 Inhibitors In The Management Of Type 2 DiabetesPk Doctors
The document discusses DPP-4 inhibitors, including sitagliptin and vildagliptin, for the treatment of type 2 diabetes. It summarizes that DPP-4 inhibitors work by inhibiting the DPP-4 enzyme, increasing active incretin levels like GLP-1 and GIP, and improving glucose control. Studies showed that both sitagliptin and vildagliptin improved glycemic measures like HbA1c and fasting glucose when used as monotherapy or add-on therapy to other diabetes medications like metformin. The document concludes that DPP-4 inhibitors are a promising new treatment option for type 2 diabetes.
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
SGLT-2 inhibitors lower blood glucose levels by reducing renal glucose reabsorption and increasing glucose excretion in the urine. Empagliflozin is a selective SGLT-2 inhibitor that lowers both fasting and post-prandial plasma glucose levels. In clinical trials, empagliflozin led to an HbA1c reduction of over 1% compared to placebo when used as both monotherapy and add-on therapy to other glucose-lowering medications. Empagliflozin was also associated with weight loss, reduced blood pressure, and a lower risk of hypoglycemia compared to sulfonylurea therapy.
This document appears to be a slide presentation given by Dr. Faraz Farishta on diabetes management. It discusses diabetes as a global health problem and challenges in achieving optimal blood sugar control, including clinical inertia. It reviews guidelines on treatment goals and limitations of conventional oral therapies. It then discusses how DPP-4 inhibitors were developed to address multiple defects in type 2 diabetes by inhibiting the breakdown of GLP-1, an incretin hormone that stimulates insulin secretion. Data is presented on the efficacy and value of the DPP-4 inhibitor vildagliptin.
Vildagliptin is a DPP-IV inhibitor used to treat type 2 diabetes. It works by inhibiting the DPP-IV enzyme, which helps increase levels of incretin hormones like GLP-1. This enhances the effects of GLP-1, including stimulating more insulin release from beta cells and suppressing glucagon secretion. Clinical studies showed vildagliptin lowers blood glucose levels and is well tolerated with a low risk of hypoglycemia and no weight gain.
This document discusses several clinical studies that compare the effects of different statin drugs on cardiovascular outcomes and the progression of atherosclerosis. The STELLAR study showed that rosuvastatin more effectively lowered LDL-C and raised HDL-C than other statins. Two real-world studies found that rosuvastatin use was associated with a 28-40% lower risk of cardiovascular events compared to other statins. The METEOR study found that rosuvastatin slowed the progression of atherosclerosis whereas the ENHANCE study found that ezetimibe added to simvastatin provided no benefit.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
This document provides an overview of a continuing medical education (CME) program on the use of vildagliptin in managing type 2 diabetes mellitus (T2DM). The presentation covers the global burden of diabetes, pathophysiology of T2DM, limitations of current oral therapies, the incretin system, and the mechanisms and effects of DPP-4 inhibitors like vildagliptin. It discusses how vildagliptin improves pancreatic beta cell function and glucose control by prolonging the actions of incretins GLP-1 and GIP. The presentation also highlights the differences between incretin mimetics and DPP-4 inhibitors.
An Update On Dpp 4 Inhibitors In The Management Of Type 2 DiabetesPk Doctors
The document discusses DPP-4 inhibitors, including sitagliptin and vildagliptin, for the treatment of type 2 diabetes. It summarizes that DPP-4 inhibitors work by inhibiting the DPP-4 enzyme, increasing active incretin levels like GLP-1 and GIP, and improving glucose control. Studies showed that both sitagliptin and vildagliptin improved glycemic measures like HbA1c and fasting glucose when used as monotherapy or add-on therapy to other diabetes medications like metformin. The document concludes that DPP-4 inhibitors are a promising new treatment option for type 2 diabetes.
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
SGLT-2 inhibitors lower blood glucose levels by reducing renal glucose reabsorption and increasing glucose excretion in the urine. Empagliflozin is a selective SGLT-2 inhibitor that lowers both fasting and post-prandial plasma glucose levels. In clinical trials, empagliflozin led to an HbA1c reduction of over 1% compared to placebo when used as both monotherapy and add-on therapy to other glucose-lowering medications. Empagliflozin was also associated with weight loss, reduced blood pressure, and a lower risk of hypoglycemia compared to sulfonylurea therapy.
This document appears to be a slide presentation given by Dr. Faraz Farishta on diabetes management. It discusses diabetes as a global health problem and challenges in achieving optimal blood sugar control, including clinical inertia. It reviews guidelines on treatment goals and limitations of conventional oral therapies. It then discusses how DPP-4 inhibitors were developed to address multiple defects in type 2 diabetes by inhibiting the breakdown of GLP-1, an incretin hormone that stimulates insulin secretion. Data is presented on the efficacy and value of the DPP-4 inhibitor vildagliptin.
Vildagliptin is a DPP-IV inhibitor used to treat type 2 diabetes. It works by inhibiting the DPP-IV enzyme, which helps increase levels of incretin hormones like GLP-1. This enhances the effects of GLP-1, including stimulating more insulin release from beta cells and suppressing glucagon secretion. Clinical studies showed vildagliptin lowers blood glucose levels and is well tolerated with a low risk of hypoglycemia and no weight gain.
This document discusses several clinical studies that compare the effects of different statin drugs on cardiovascular outcomes and the progression of atherosclerosis. The STELLAR study showed that rosuvastatin more effectively lowered LDL-C and raised HDL-C than other statins. Two real-world studies found that rosuvastatin use was associated with a 28-40% lower risk of cardiovascular events compared to other statins. The METEOR study found that rosuvastatin slowed the progression of atherosclerosis whereas the ENHANCE study found that ezetimibe added to simvastatin provided no benefit.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Recent studies have highlighted the growing global burden of type 2 diabetes, with over 600 million people projected to have the disease by 2045. In particular, Egypt will face explosive growth in cases. While control of blood sugar levels is important for reducing complications, most patients do not achieve treatment goals. Intensifying treatment in a timely manner when blood sugar is poorly controlled can reduce cardiovascular risks. Inertia on the part of both physicians and healthcare systems often limits timely treatment changes needed to improve outcomes for patients with type 2 diabetes.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
1) Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that works by inhibiting glucose reabsorption in the kidney and increasing glucose excretion in the urine.
2) Studies have shown that dapagliflozin reduces HbA1c and body weight when used as monotherapy or as add-on therapy to other glucose-lowering medications, including metformin, sulfonylureas, pioglitazone, and insulin. Reductions in HbA1c were sustained over 102 weeks.
3) Common side effects of dapagliflozin include increased urinary tract and genital infections, as well
Dapagliflozin is an SGLT2 inhibitor that has shown benefits in managing type 2 diabetes and reducing cardiovascular outcomes. The document summarizes results from several key studies on dapagliflozin. The DECLARE-TIMI trial showed that dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure compared to placebo in patients with type 2 diabetes with high cardiovascular risk. The DAPA-HF trial found that dapagliflozin reduced the risks of worsening heart failure or cardiovascular death compared to placebo in patients with heart failure regardless of diabetes status. Dapagliflozin also improved outcomes related to heart failure in the DEFINE-HF trial.
- DPP-4 inhibitors like vildagliptin work by inhibiting the DPP-4 enzyme, which helps increase levels of incretin hormones like GLP-1. This can improve insulin secretion and suppress glucagon secretion from the islet cells.
- A clinical trial found that adding vildagliptin to metformin therapy produced greater reductions in HbA1c and fasting plasma glucose compared to metformin alone. It also enhanced beta-cell function and improved postprandial glucose levels.
- Initial combination therapy of vildagliptin and metformin was effective across a range of baseline HbA1c levels, with more patients achieving an HbA1c under 7% compared to sulf
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
The document discusses the role of the kidney in glucose regulation. The kidney releases glucose into the bloodstream via gluconeogenesis in the renal cortex and takes up glucose from the blood for energy in the renal medulla. The kidney also reabsorbs glucose from the proximal convoluted tubule. SGLT2 inhibitors like canagliflozin, dapagliflozin, and empagliflozin work by inhibiting glucose reabsorption in the kidney, thereby increasing glucose excretion and lowering blood glucose levels. They provide glycemic control with a low risk of hypoglycemia when used alone but a higher risk when combined with insulin or insulin secretagogues. Side effects include genital infections, urinary
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
This document discusses the use of SGLT2 inhibitors (SGLT2i) in managing diabetes. It presents three case studies of patients with diabetes and cardiovascular complications who may benefit from SGLT2i treatment. It summarizes clinical trial data showing that empagliflozin lowers HbA1c, fasting plasma glucose, body weight, and blood pressure compared to other antidiabetic drugs. Empagliflozin also reduces visceral and subcutaneous fat. The document concludes that SGLT2i like empagliflozin provide glycemic control and cardiovascular benefits and can be considered as an addition to metformin for treating diabetes.
A 52-year-old man with type 2 diabetes of 8 years was uncontrolled on insulin therapy and gaining weight. He was obese, had hypertension and dyslipidemia. Dapagliflozin was added to his insulin regimen while reducing his insulin dose by 25%. This led to reductions in his HbA1c, weight, blood pressure, and lipid levels over 6 months of follow up while preventing further increases to his insulin needs. Dapagliflozin provided glycemic control and weight loss without increasing hypoglycemia risk for this patient with multiple comorbidities.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that enhances glucose-dependent insulin secretion from pancreatic beta cells. GLP-1 levels are reduced in patients with type 2 diabetes. Therapeutic strategies that augment the GLP-1 pathway include GLP-1 receptor agonists such as exenatide and liraglutide, as well as dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the breakdown of endogenous GLP-1. These incretin-based therapies lower blood glucose levels with a low risk of hypoglycemia and promote weight loss, offering an important treatment option for patients with type 2 diabetes.
This document summarizes the key properties of 8 DPP-4 inhibitor drugs used to treat type 2 diabetes: alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin. It provides details on their mechanism of action, pharmacokinetic properties like bioavailability and half-life, FDA approval status, and evidence from clinical trials demonstrating their efficacy in reducing HbA1c levels and safety. The document concludes that DPP-4 inhibitors are a promising class of antidiabetic drugs that improve glycemic control without weight gain or hypogly
Ueda2016 symposium - glimepiride journey in management of type 2 dm - megahe...ueda2015
This document discusses glimepiride and its use in managing type 2 diabetes mellitus (T2DM). It begins with background on the global prevalence of diabetes and challenges in achieving glycemic control. It then focuses on glimepiride, explaining that it has a higher binding affinity and faster dissociation from sulfonylurea receptors compared to other sulfonylureas. This allows glimepiride to stimulate both the first and second phase of insulin secretion, improving fasting and postprandial hyperglycemia. In conclusion, glimepiride is an effective oral sulfonylurea option for the treatment of T2DM.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
This document summarizes the history and mechanisms of action of SGLT2 inhibitors, a class of diabetes medications. Key points include:
- SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, inducing glucosuria and lowering blood glucose levels.
- Several large clinical trials demonstrated SGLT2 inhibitors effectively lower HbA1c and blood glucose with a low risk of hypoglycemia compared to other diabetes medications.
- Beyond glycemic control, SGLT2 inhibitors provide additional benefits like weight loss, blood pressure reduction, and improved cardiac outcomes.
Empagliflozin is an SGLT2 inhibitor that has shown cardiovascular benefits in clinical trials. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, leading to increased glucose excretion and reduced blood glucose levels. Empagliflozin in particular has demonstrated reductions in cardiovascular death and hospitalization for heart failure. However, SGLT2 inhibitors also carry risks like genitourinary infections and volume depletion that require monitoring. Overall, SGLT2 inhibitors provide an additional treatment option for type 2 diabetes that can help lower glucose levels while also reducing cardiovascular outcomes.
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
Sodium glucose co transporter( SGLT2) Inhibitors Philip Vaidyan
This document discusses sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of drugs for treating type 2 diabetes. SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, increasing urinary glucose excretion in a glucose-dependent manner. Three SGLT2 inhibitors have been approved by the FDA - canagliflozin, dapagliflozin, and empagliflozin. SGLT2 inhibitors offer advantages over other anti-diabetic drugs in that they are non-insulin dependent and can be used throughout the course of diabetes. However, long-term safety studies are still needed to fully assess their risk-benefit profile.
Silvio E. Inzucchi, MD, prepared useful Practice Aids pertaining to type 2 diabetes management for this CME activity titled "The Role of SGLT2 Inhibitors in Type 2 Diabetes: CV, Metabolic, and Renal Considerations." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2l4h3Ss. CME credit will be available until June 27, 2019.
Ueda2016 symposium - management of type 2 dm overcoming the challenges - mes...ueda2015
This document provides guidance on the management of type 2 diabetes mellitus (T2DM). It discusses factors to consider when choosing oral antidiabetic drugs (OADs), including efficacy, safety, effect on weight and comorbidities. Dipeptidyl peptidase-4 (DPP-4) inhibitors like linagliptin are recommended as part of dual or triple therapy if HbA1c targets are not met with other agents. Linagliptin has advantages over other DPP-4 inhibitors in that it is primarily excreted unchanged in bile and does not require dose adjustment in patients with renal impairment. The document provides treatment algorithms for achieving glycemic control in T2DM
DPP-4 inhibitors work by inhibiting the DPP-4 enzyme, which normally breaks down the incretin hormones GLP-1 and GIP. By inhibiting DPP-4, GLP-1 levels are increased for longer after meals. This helps lower blood sugar levels by stimulating insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. DPP-4 inhibitors are used to treat type 2 diabetes, either alone or in combination with other drugs like metformin. They improve glycemic control as measured by HbA1c levels and have benefits like weight neutrality and low risk of hypoglycemia. However, some studies have found possible links between DPP-4 inhibitors and side effects like pancreatitis
Recent studies have highlighted the growing global burden of type 2 diabetes, with over 600 million people projected to have the disease by 2045. In particular, Egypt will face explosive growth in cases. While control of blood sugar levels is important for reducing complications, most patients do not achieve treatment goals. Intensifying treatment in a timely manner when blood sugar is poorly controlled can reduce cardiovascular risks. Inertia on the part of both physicians and healthcare systems often limits timely treatment changes needed to improve outcomes for patients with type 2 diabetes.
This document discusses glucose-lowering therapies and the clinical place of SGLT2 inhibitor agents. It presents the case of a 52-year-old male patient with type 2 diabetes, hypertension, and coronary artery disease. It analyzes adding empagliflozin or sitagliptin to the patient's current metformin regimen and reviews long-term trial data showing empagliflozin's superior effects on HbA1c reduction, weight loss, and hypoglycemia risk reduction compared to glimepiride. The document also discusses empagliflozin's benefits on blood pressure and potential cardioprotective mechanisms of action beyond glycemic control such as reducing cardiac fibrosis. It emphasizes the importance of individual
1) Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that works by inhibiting glucose reabsorption in the kidney and increasing glucose excretion in the urine.
2) Studies have shown that dapagliflozin reduces HbA1c and body weight when used as monotherapy or as add-on therapy to other glucose-lowering medications, including metformin, sulfonylureas, pioglitazone, and insulin. Reductions in HbA1c were sustained over 102 weeks.
3) Common side effects of dapagliflozin include increased urinary tract and genital infections, as well
Dapagliflozin is an SGLT2 inhibitor that has shown benefits in managing type 2 diabetes and reducing cardiovascular outcomes. The document summarizes results from several key studies on dapagliflozin. The DECLARE-TIMI trial showed that dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure compared to placebo in patients with type 2 diabetes with high cardiovascular risk. The DAPA-HF trial found that dapagliflozin reduced the risks of worsening heart failure or cardiovascular death compared to placebo in patients with heart failure regardless of diabetes status. Dapagliflozin also improved outcomes related to heart failure in the DEFINE-HF trial.
- DPP-4 inhibitors like vildagliptin work by inhibiting the DPP-4 enzyme, which helps increase levels of incretin hormones like GLP-1. This can improve insulin secretion and suppress glucagon secretion from the islet cells.
- A clinical trial found that adding vildagliptin to metformin therapy produced greater reductions in HbA1c and fasting plasma glucose compared to metformin alone. It also enhanced beta-cell function and improved postprandial glucose levels.
- Initial combination therapy of vildagliptin and metformin was effective across a range of baseline HbA1c levels, with more patients achieving an HbA1c under 7% compared to sulf
Sitagliptin an oral anti-diabetic agentAmruta Vaidya
A concise presentation on the DPP-IV inhibitor Sitagliptin an oral anti-diabetic agent. Its general mechanism of action, pharmacokinetics, safety is included.
The document discusses the role of the kidney in glucose regulation. The kidney releases glucose into the bloodstream via gluconeogenesis in the renal cortex and takes up glucose from the blood for energy in the renal medulla. The kidney also reabsorbs glucose from the proximal convoluted tubule. SGLT2 inhibitors like canagliflozin, dapagliflozin, and empagliflozin work by inhibiting glucose reabsorption in the kidney, thereby increasing glucose excretion and lowering blood glucose levels. They provide glycemic control with a low risk of hypoglycemia when used alone but a higher risk when combined with insulin or insulin secretagogues. Side effects include genital infections, urinary
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
This document discusses the use of SGLT2 inhibitors (SGLT2i) in managing diabetes. It presents three case studies of patients with diabetes and cardiovascular complications who may benefit from SGLT2i treatment. It summarizes clinical trial data showing that empagliflozin lowers HbA1c, fasting plasma glucose, body weight, and blood pressure compared to other antidiabetic drugs. Empagliflozin also reduces visceral and subcutaneous fat. The document concludes that SGLT2i like empagliflozin provide glycemic control and cardiovascular benefits and can be considered as an addition to metformin for treating diabetes.
A 52-year-old man with type 2 diabetes of 8 years was uncontrolled on insulin therapy and gaining weight. He was obese, had hypertension and dyslipidemia. Dapagliflozin was added to his insulin regimen while reducing his insulin dose by 25%. This led to reductions in his HbA1c, weight, blood pressure, and lipid levels over 6 months of follow up while preventing further increases to his insulin needs. Dapagliflozin provided glycemic control and weight loss without increasing hypoglycemia risk for this patient with multiple comorbidities.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that enhances glucose-dependent insulin secretion from pancreatic beta cells. GLP-1 levels are reduced in patients with type 2 diabetes. Therapeutic strategies that augment the GLP-1 pathway include GLP-1 receptor agonists such as exenatide and liraglutide, as well as dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the breakdown of endogenous GLP-1. These incretin-based therapies lower blood glucose levels with a low risk of hypoglycemia and promote weight loss, offering an important treatment option for patients with type 2 diabetes.
This document summarizes the key properties of 8 DPP-4 inhibitor drugs used to treat type 2 diabetes: alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin. It provides details on their mechanism of action, pharmacokinetic properties like bioavailability and half-life, FDA approval status, and evidence from clinical trials demonstrating their efficacy in reducing HbA1c levels and safety. The document concludes that DPP-4 inhibitors are a promising class of antidiabetic drugs that improve glycemic control without weight gain or hypogly
Ueda2016 symposium - glimepiride journey in management of type 2 dm - megahe...ueda2015
This document discusses glimepiride and its use in managing type 2 diabetes mellitus (T2DM). It begins with background on the global prevalence of diabetes and challenges in achieving glycemic control. It then focuses on glimepiride, explaining that it has a higher binding affinity and faster dissociation from sulfonylurea receptors compared to other sulfonylureas. This allows glimepiride to stimulate both the first and second phase of insulin secretion, improving fasting and postprandial hyperglycemia. In conclusion, glimepiride is an effective oral sulfonylurea option for the treatment of T2DM.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
This document summarizes the history and mechanisms of action of SGLT2 inhibitors, a class of diabetes medications. Key points include:
- SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, inducing glucosuria and lowering blood glucose levels.
- Several large clinical trials demonstrated SGLT2 inhibitors effectively lower HbA1c and blood glucose with a low risk of hypoglycemia compared to other diabetes medications.
- Beyond glycemic control, SGLT2 inhibitors provide additional benefits like weight loss, blood pressure reduction, and improved cardiac outcomes.
Empagliflozin is an SGLT2 inhibitor that has shown cardiovascular benefits in clinical trials. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, leading to increased glucose excretion and reduced blood glucose levels. Empagliflozin in particular has demonstrated reductions in cardiovascular death and hospitalization for heart failure. However, SGLT2 inhibitors also carry risks like genitourinary infections and volume depletion that require monitoring. Overall, SGLT2 inhibitors provide an additional treatment option for type 2 diabetes that can help lower glucose levels while also reducing cardiovascular outcomes.
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
Sodium glucose co transporter( SGLT2) Inhibitors Philip Vaidyan
This document discusses sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of drugs for treating type 2 diabetes. SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, increasing urinary glucose excretion in a glucose-dependent manner. Three SGLT2 inhibitors have been approved by the FDA - canagliflozin, dapagliflozin, and empagliflozin. SGLT2 inhibitors offer advantages over other anti-diabetic drugs in that they are non-insulin dependent and can be used throughout the course of diabetes. However, long-term safety studies are still needed to fully assess their risk-benefit profile.
Silvio E. Inzucchi, MD, prepared useful Practice Aids pertaining to type 2 diabetes management for this CME activity titled "The Role of SGLT2 Inhibitors in Type 2 Diabetes: CV, Metabolic, and Renal Considerations." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2l4h3Ss. CME credit will be available until June 27, 2019.
Ueda2016 symposium - management of type 2 dm overcoming the challenges - mes...ueda2015
This document provides guidance on the management of type 2 diabetes mellitus (T2DM). It discusses factors to consider when choosing oral antidiabetic drugs (OADs), including efficacy, safety, effect on weight and comorbidities. Dipeptidyl peptidase-4 (DPP-4) inhibitors like linagliptin are recommended as part of dual or triple therapy if HbA1c targets are not met with other agents. Linagliptin has advantages over other DPP-4 inhibitors in that it is primarily excreted unchanged in bile and does not require dose adjustment in patients with renal impairment. The document provides treatment algorithms for achieving glycemic control in T2DM
DPP-4 inhibitors work by inhibiting the DPP-4 enzyme, which normally breaks down the incretin hormones GLP-1 and GIP. By inhibiting DPP-4, GLP-1 levels are increased for longer after meals. This helps lower blood sugar levels by stimulating insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. DPP-4 inhibitors are used to treat type 2 diabetes, either alone or in combination with other drugs like metformin. They improve glycemic control as measured by HbA1c levels and have benefits like weight neutrality and low risk of hypoglycemia. However, some studies have found possible links between DPP-4 inhibitors and side effects like pancreatitis
DPP-4 inhibitors work by inhibiting the breakdown of the incretin hormones GLP-1 and GIP, prolonging their effects and enhancing insulin secretion. They reduce blood glucose levels with a low risk of hypoglycemia and are weight neutral. Several DPP-4 inhibitors are available or in development for treating type 2 diabetes, including sitagliptin, saxagliptin, and linagliptin. DPP-4 inhibitors offer an effective treatment either alone or in combination with other drugs, with advantages like fewer side effects, safety in hepatic or renal impairment, and possible cardiovascular benefits. More research is still needed to fully evaluate their long-term safety profile.
The document discusses drugs for type 2 diabetes that are inhibitors of DPP-4, including sitagliptin, vildagliptin, saxagliptin, alogliptin, and linagliptin. It lists the generic and brand names of the drugs, along with their companies and FDA approval dates in the United States and European Union.
This document summarizes key information about DPP-4 inhibitors for the treatment of type 2 diabetes. It begins by outlining the growing prevalence of diabetes worldwide and in the Middle East/North Africa. It then discusses the pathophysiology of type 2 diabetes, focusing on the incretin defect and role of DPP-4 inhibitors. The document reviews the mechanisms of action, selectivity profiles, and pharmacokinetic differences between various DPP-4 inhibitors. Head-to-head trials demonstrate comparable efficacy of sitagliptin versus sulfonylureas, with sitagliptin showing much lower risk of hypoglycemia. The document concludes DPP-4 inhibitors are effective options for glycemic control with a
- T2DM accounts for 90-95% of all diagnosed diabetes cases. It is a growing epidemic affecting 246 million people worldwide in 2007.
- The main pathophysiology of T2DM includes insulin resistance in muscle, liver and fat tissues as well as insulin deficiency due to impaired insulin secretion from pancreatic beta cells over time.
- Current treatment options for T2DM like metformin, sulfonylureas and thiazolidinediones have limitations such as side effects of weight gain, hypoglycemia, edema and heart failure which impact efficacy and safety.
Esta ha sido una de las conferencias que mas me ha gustado darla por lo moderno en el tratamiento de la DBM tipo 2 ,con el uso de la Linagliptina completamos el cuadro
This document summarizes a clinical presentation on the basal insulin degludec and barriers to achieving optimal glycemic control. It discusses that hypoglycemia and glucose variability are barriers, and that current basal insulins have limitations like needing to be dosed at the same time daily and intra-patient variability. Insulin degludec was developed to address these barriers with properties like an ultra-long half-life of over 25 hours, very low day-to-day variability in glucose-lowering effect, and the ability to reach steady-state in 3 days. Large clinical trials showed degludec was as effective as glargine at reducing A1c and had a similar or lower risk of hyp
The document discusses the "glucose triad" which refers to the relationship between HbA1c, fasting plasma glucose, and postprandial plasma glucose in glycemic control. It notes that while HbA1c has traditionally been the target, more recent studies show intensive control to reach very low HbA1c levels may be detrimental. The document explores how the relationship between the components of the glucose triad changes over time as diabetes progresses, with postprandial glucose being more influential at lower HbA1c levels and fasting glucose becoming more important at higher levels. Treatment should target both fasting and postprandial hyperglycemia simultaneously for optimal control.
Drug discovery and development process of anti diabetic plants, Prof. Dr. Basavaraj K. Nanjwade, KLE University College of Pharmacy, Belgavi/Belgaum, Karnataka, India.
The SAVOR-TIMI 53 trial investigated the cardiovascular outcomes of adding saxagliptin to standard care in 16,492 patients with type 2 diabetes and high cardiovascular risk over a median of 2.1 years. The primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 11.3% of the saxagliptin group and 11.8% of the placebo group, demonstrating saxagliptin's noninferiority. However, hospitalization for heart failure occurred more frequently in the saxagliptin group. The TECOS trial of 14,671 patients with type 2 diabetes, established cardiovascular disease, and inadequate glycemic control investigated adding sitagliptin or placebo to
Los cuatro casos clínicos presentados involucran a pacientes con diabetes tipo 2 con mal control glucémico que fueron tratados con vildagliptina. En el primer caso, el cambio a una combinación fija de vildagliptina y metformina mejoró el control glucémico y redujo el peso del paciente. En el segundo caso, el cambio desde una sulfonilurea a vildagliptina mejoró las hipoglucemias frecuentes y el control glucémico. En el tercer caso, la adición de vildagliptina a la sulf
This study compared the effects of vildagliptin twice daily and sitagliptin once daily on blood glucose levels in 20 patients with type 2 diabetes using continuous glucose monitoring. The mean 24-hour blood glucose level and mean amplitude of glycemic excursions were significantly lower in patients taking vildagliptin compared to sitagliptin. Vildagliptin also resulted in significantly lower highest post-meal blood glucose levels and less hyperglycemia after breakfast. There were no significant differences in BNP and PAI-1 levels between the two drugs. The study concluded that vildagliptin more effectively lowered blood glucose levels and fluctuations compared to sitagliptin.
Here are some key points about adding another agent best suited to the individual:
- α-glucosidase inhibitors like acarbose lower A1C moderately, rarely cause hypoglycemia, are weight neutral or may cause weight loss, and have shown improved postprandial glucose control and cardiovascular outcomes in some studies. They require multiple daily doses with meals.
- DPP-4 inhibitors like sitagliptin, saxagliptin and linagliptin lower A1C moderately, have a low risk of hypoglycemia, are weight neutral, and have generally shown neutral cardiovascular outcomes. They are well tolerated with once daily dosing.
- GLP-1 receptor agonists like exen
Our aim is to reduce morbidity and mortality related to Non communicable diseases such as hypertension, diabetes, cardiovascular disease, stroke, Obesity, Cancer and lifestyle diseases among those least able to withstand the burden of the disease.
Ueda2016 symposium -t2 dm management - lobna el toonyueda2015
Sitagliptin improves glycemic control in a glucose-dependent manner by increasing concentrations of active incretin hormones like GLP-1. It targets the metabolic defects of type 2 diabetes by improving markers of beta-cell function, reducing hepatic glucose overproduction, and having insulin-sensitizing properties. Studies show sitagliptin is associated with a lower risk of hypoglycemia and less weight gain compared to sulfonylureas when added to metformin. It also provides durable glycemic control with a lower risk of requiring additional antihyperglycemic medications over time.
The document discusses the role of DPP-4 inhibition and sitagliptin in the management of type 2 diabetes. It provides evidence that sitagliptin increases active GLP-1 and GIP levels, resulting in improved glycemic control through increased insulin secretion, decreased glucagon levels, and reduced glucose levels. Studies show sitagliptin to be an effective monotherapy and when added to other oral medications, with benefits seen within days and a generally well-tolerated safety profile compared to sulfonylureas.
Ueda2015 lilly.the art of insulin dr.mesbah sayedueda2015
This document discusses the treatment of a 52-year-old patient with type 2 diabetes who has an HbA1c of 9.4% despite treatment with oral medications. It considers adding insulin therapy to help control the patient's blood glucose levels and reach treatment targets. Specifically, it compares the effectiveness of premixed insulin versus basal insulin when initiating insulin in type 2 diabetes patients. A study is summarized that found premixed insulin administered twice daily in combination with metformin was more effective at reducing HbA1c and post-prandial blood glucose compared to a basal insulin administered once daily plus metformin. The document advocates for patient-centered treatment approaches and discusses factors to consider when choosing between premixed versus basal-bolus insulin reg
A 63-year-old man with a history of IHD, 1VD, HTN, hyperlipidemia, and an HbA1c of 8.2% is taking 26 units of insulin glargine daily. His LDL is 80 mg/dL and TG is 160 mg/dL. His BMI is 26. The document discusses treatment options with pioglitazone given his medical history and risk factors. Pioglitazone has been shown to improve insulin sensitivity and reduce cardiovascular events and microvascular complications in patients with type 2 diabetes when used as monotherapy or in combination with other antidiabetic agents. However, pioglitazone can cause side effects like edema,
1) The document discusses the incretin effect and how it is diminished in patients with type 2 diabetes. It also reviews the mechanisms of action and protraction of the GLP-1 receptor agonist Liraglutide.
2) Guidelines position Liraglutide as an effective add-on therapy to metformin for the treatment of type 2 diabetes, with efficacy in lowering A1c and promoting weight loss.
3) Clinical trials demonstrate Liraglutide significantly reduces A1c by up to 1.6% and promotes weight loss of up to 7.7 kg on average in a quartile of patients when used as an add-on therapy to metformin.
This document summarizes findings from several studies related to cardiovascular protection in type 2 diabetes patients. It begins by noting that atherosclerosis and diabetes often have common antecedents. A framingham offspring study found that 2/3 of diabetes patients have subclinical cardiovascular disease, which increases their cardiovascular risk 4-fold. Another study found that 66-74% of asymptomatic South Asian type 2 diabetes patients have coronary artery disease. The document then notes that subclinical cardiovascular disease affects over 2/3 of diabetes patients, and that cardiovascular complications form a progressive continuum in type 2 diabetes, with heart failure developing early. It reviews findings on cardiovascular risk prior to diabetes diagnosis and the cardiovascular risk continuum in dysglycemia. The document discusses challenges with long
The use of vildagliptin in patients with type 2 diabetes with renal impairmentUsama Ragab
The use of vildagliptin in patients with type 2 diabetes with renal impairment
By Dr. Usama Ragab Youssif
Agenda
----------
Case presentation
Diabetes and CKD: What is the problem
Drug treatment in patient with CKD: choice of treatment
Vildagliptin in mild renal impairment
Vildagliptin in moderate and severe renal impairment
Vildagliptin in ESRD (patients on HD)
Vildagliptin in kidney transplant patients with NODAT
Final bottom-line
The document discusses type 2 diabetes mellitus (T2DM) and strategies for achieving glycemic targets. It notes the increasing complexity of T2DM management given the variety of treatment options available and concerns about intensive control. The document summarizes guidelines recommending individualized glycemic targets and avoidance of hypoglycemia. It also reviews studies showing that sitagliptin added to metformin or insulin therapy was effective at lowering blood sugar levels compared to other agents, with a lower risk of hypoglycemia and weight gain.
This document discusses the clinical profile and efficacy of the combination drug GLYXAMBI, which contains empagliflozin and linagliptin. It summarizes clinical trial results showing that GLYXAMBI provides significant reductions in HbA1c and body weight compared to the individual components alone in patients with type 2 diabetes. Guidelines from major diabetes organizations have been updated to recommend SGLT2 inhibitors like empagliflozin and GLP-1 receptor agonists to reduce cardiovascular risk based on positive cardiovascular outcomes trial results.
1) Current diabetes treatments often fail to achieve glycemic targets over time and treatment related issues like weight gain and hypoglycemia can decrease tight glycemic control.
2) HbA1c alone does not provide a full picture of glycemic fluctuations and both fasting and post-prandial glucose need to be addressed.
3) A more comprehensive approach is needed to glycemic management that minimizes weight gain and hypoglycemia and achieves and maintains tight long-term control.
The document discusses type 2 diabetes and the role of incretin hormones like GLP-1 and GIP. It notes that patients with type 2 diabetes have impaired secretion and actions of incretins. Dipeptidyl peptidase-4 (DPP-4) inhibitors work by blocking the degradation of incretins, thereby increasing their levels and effects. Clinical trials show that sitagliptin (Januvia), a DPP-4 inhibitor, improves glycemic control in type 2 diabetes patients by enhancing the actions of endogenous GLP-1 and GIP.
Combining insulin and GLP-1 receptor agonists like Victoza provides complementary benefits for managing type 2 diabetes. Studies show adding Victoza to basal insulin regimens results in: improved glycemic control as shown by greater reductions in HbA1c levels of around 1%; weight loss or weight neutral effects compared to weight gain with insulin alone; and a low risk of hypoglycemia. The combination helps address insulin's limitations of weight gain and variability in glucose lowering by enhancing insulin's effects and reducing glucagon secretion from Victoza. Overall, combining these therapies provides effective glycemic control while minimizing side effects.
Similar to Achieving Treatment Outcome With DPP4i for Diabetic Patient "Efficacy Beyond Sugar Control” (20)
Marcellus Simadibrata Kolopaking MD PhD
Department of Medical Education
Division Gastroenterology Department of Internal Medicine
Faculty of Medicine University Indonesia
Dr.Cipto Mangunkusumo Hospital Jakarta
Penanganan Neurointervensipada kasus kasus StrokeSuharti Wairagya
Dokumen tersebut membahas penanganan neurointervensi pada kasus stroke. Metode penanganan meliputi trombolisis untuk stroke iskemik menggunakan obat rtPA dalam 4,5 jam secara IV atau 6 jam secara IA, trombektomi dalam 8 jam, serta stenting dan angioplasti untuk stenosis pembuluh darah. Metode lainnya adalah embolisasi untuk perdarahan guna mencegah rebleeding, dan penanganan aneurysma menggunakan coil. Parameter skor digun
Achieving Blood Pressure Goal: From Clinical Trial into Real-World DataSuharti Wairagya
Hypertension remains a major global health issue, with over 7 million deaths annually associated with it. Less than 50% of hypertensive patients receive therapy, and approximately 70% of treated patients do not reach blood pressure goals. Most guidelines recommend initiating treatment with two drugs when blood pressure is more than 20/10 mmHg above goal or for those at high cardiovascular risk. Clinical trials have shown that the amlodipine/valsartan combination effectively lowers blood pressure and helps more patients achieve goals compared to monotherapy. Real-world Indonesian studies found that amlodipine/valsartan combination therapy was effective at controlling blood pressure in the majority of uncontrolled hypertensive patients switched from monotherapy.
PENATALAKSANAAN TERKINI PENYAKIT KULIT DALAM PRAKTEK SEHARI HARI Suharti Wairagya
Pada dokumen tersebut membahas tentang penatalaksanaan terkini penyakit kulit dalam praktek sehari-hari. Dokumen ini memberikan ringkasan singkat tentang berbagai topik infeksi kulit seperti varicella, herpes zoster, herpes simpleks, impetigo, erisipelas, selulitis, kusta dan reaksi kustanya, serta kandidiasis dan dermatofilosis.
1. Gangguan haid memiliki berbagai spektrum yang meliputi amenore, perdarahan uterus abnormal, dan dismenore.
2. Perdarahan uterus abnormal dapat disebabkan oleh faktor struktural dan nonstruktural seperti kelainan ovarium, leiomioma, adenomiosis, koagulopati, dan gangguan ovulasi.
3. Diagnosis perdarahan uterus abnormal memerlukan investigasi umum dan sistematis mulai dari layanan kesehatan primer untuk menyingkirkan penyebabnya.
Dokumen tersebut membahas tentang penatalaksanaan gangguan cemas, termasuk epidemiologi, gejala, diagnosis, peran neurotransmiter, dan terapi gangguan cemas seperti gangguan panik, gangguan cemas menyeluruh, fobia sosial, dan gangguan obsesif kompulsif."
Controversy: the role of immunomodulator in allergic caseSuharti Wairagya
dipresentasikan oleh Erwanto BW Teguh HK
Divisi Alergi Imunologi Klinik Departemen 1. Penyakit Dalam FKUI/RSCM Bagian Penyakit Dalam SMF non Bedah RS. dr. H. Marzoeki Mahdi Bogor
Neuropati perifer adalah gangguan saraf perifer yang dapat mengenai sensorik, motorik, atau otonom. Diagnosis tepat membutuhkan anamnesa lengkap dan pemeriksaan fisik neurologi. Kasus akut seperti Guillain-Barre dan Bell's Palsy memerlukan diagnosis cepat dan penanganan awal untuk memperbaiki prognosis.
Tiga kalimat ringkasan dokumen tersebut adalah:
Dokumen tersebut membahas tentang demensia Alzheimer, termasuk gejala, penyebab, pemeriksaan diagnosis, dan penatalaksanaannya seperti terapi farmakologi. Demensia Alzheimer merupakan jenis demensia paling umum yang disebabkan oleh degenerasi dan kematian neuron di otak.
Early Treatment to Manage Hyperglycemia: Do We Have Enough Option Dr olly tr...Suharti Wairagya
This document discusses early treatment options for managing hyperglycemia in type 2 diabetes. It begins by outlining the symptoms, signs, and diagnostic criteria for diabetes. It then discusses the pathophysiology of type 2 diabetes, focusing on pancreatic beta cell dysfunction and insulin resistance over time. The document examines various oral medications for managing blood glucose levels, including their mechanisms of action, efficacy, safety profiles, and rationale for combination therapy. It emphasizes that the ideal treatment would address all key aspects of disease progression like glucose control, weight, cardiovascular risk, and beta cell function while minimizing hypoglycemia.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
2. Riwayat Hidup :
Nama : Dr Eddy Supriadi, Sp.PD, FINASIM
Tempat/ Tgl. Lahir : Jakarta, 19 Feb 1968
Pendidikan : Dokter FKUI 1993, Penyakit Dalam
FKUI 2006
Tempat Kerja : RS Dr H. MARZOEKI MAHDI
Pengalaman :
- Inspire Diabetes Program. PERKENI Indonesia-
STENO Denmark. Jakarta 2013.
- Workshop and Symposium on the Diabetic Foot.
Noordwijkerhout, The Netherlands, 2011
- dll.
3. The Prevalence of Diabetes Mellitus Worldwide
(IDF 2013) Diabetes Atlas 3
6. Classification and Diagnosis of Diabetes
6
A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A random plasma glucose ≥200 mg/dL
(11.1 mmol/L)
ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9; Table 2.1
7. Categories of Increased Risk for Diabetes
(Prediabetes)*
7
FPG 100–125 mg/dL (5.6–6.9 mmol/L): IFG
OR
2-h plasma glucose in the 75-g OGTT
140–199 mg/dL (7.8–11.0 mmol/L): IGT
OR
A1C 5.7–6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and becoming
disproportionately greater at higher ends of the range.
ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S10; Table 2.3
8. Approach to the Management of
Hyperglycemia
8
ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37. Figure 6.1; adapted with
permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149
9. Antihyperglycemic Therapy in
Type 2 Diabetes
9
If not controlled
in
3 months
3 months
3 months
ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S43. Figure 7.1;
adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149
13. Different Binding Kinetics within DPP-4 Class
Natural
substrate:
(GLP-1)
GLP-1
+
DPP-4
K-1
K1
GLP-1: DPP-4
complex
K2
Fast
(~1 sec)
DPP-4Inactive
GLP-1
+
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1.
Burkey BF, et al. Poster 0788 presented at EASD 2006; Deacon CF, Holst JJ. Adv Ther. 2009; 26: 488–499;
Miller SA, St Onge EL. Ann Pharmacother. 2006; 40: 1336–1343; Neumiller JJ. J Am Pharm Assoc. 2009; 49: S16–S29;
Potashman MH & Duggan ME. J Med Chem 2009; 52: 1231-1246. White JR. Clin Diabetes. 2008; 26: 53–57.
Substrate
acting as
inhibitor:
(vildagliptin,
saxagliptin) Substrate-like
enzyme blocker
+
DPP-4
K-1
K1
Substrate-like
enzyme blocker:
DPP-4 complex
K2
Slow
(~ 1 h)
DPP-4Inactive
substrate-like
enzyme blocker
+
Slow dissociation
Inhibitor
+
DPP-4
K-1
K1
Inhibitor: DPP-4
complex
Competitive
inhibitor:
(sitagliptin,
alogliptin) Fast dissociation
13
14. DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1. Burkey BF, et al. Poster 0788 presented at EASD 2006; Deacon CF, Holst JJ. Adv Ther.
2009; 26: 488–499; Miller SA, St Onge EL. Ann Pharmacother. 2006; 40: 1336–1343; Neumiller JJ. J Am Pharm Assoc. 2009; 49: S16–S29; Potashman
MH, Duggan ME. J Med Chem 2009; 52: 1231–1246; White JR. Clin Diabetes. 2008; 26: 53–57.
Fast dissociation Slow dissociation
GLP-1
GLP-1
GLP-1
DPP-4
Competitive
inhibitor
GLP-1
GLP-1
GLP-1
DPP-4
Vildagliptin
Tight substrate-like binding of vildagliptin leads to
potent DPP-4 inhibition
Duration of sitagliptin binding: <5 seconds Duration of vildagliptin binding: 55 minutes
14
15. 0
20
40
60
80
100
120
-2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Vildagliptin 50 mg twice daily
Sitagliptin 100 mg once daily
Relationship between Drug Exposure and GLP-1 Levels
with Vildagliptin and SitagliptinDrugLevels
Drug exposure1
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1. *P <0.05 vs vildagliptin group.
Plasma levels during 24-h sampling comprising three standardized meals after 3 months of treatment in type 2 diabetic patients.
1He YL, et al. Clin Pharmacokinet. 2007; 46: 577–588; 1Herman GA, et al. Clin Pharmacol Ther. 2005; 78: 675–688;
2Marfella R, et al. J Diabetes Complications. 24: 79-83, 2009.
IntactGLP-1(pmol/L)
Time (hours)
0 2 4 6 8 10 12 14 16
0
5
10
15
20
25
30
Breakfast Lunch Dinner
Vildagliptin 50 mg twice daily
Sitagliptin 100 mg once daily
Time (hours)
GLP-1 levels2
15
16. Comparison of Plasma Glucagon Levels following
3 Months’ Treatment with Vildagliptin or Sitagliptin
Sitagliptin 100 mg once
daily + metformin (N=20)
Vildagliptin 50 mg
twice daily + metformin (N=18)
*P <0.05 vs vildagliptin group; Plasma levels during 24-h sampling comprising three
standardized meals after 3 months of treatment in type 2 diabetic patients.
Marfella R, et al. J Diabetes Complications. 24: 79-83, 2009.
90
80
70
60
50
40
30
20
Breakfast Lunch Dinner
PlasmaGlucagon(mg/dL)
-20 0 15 30 60 90 120 180 240 300 0 15 3060 90 120 180 240 300 0 15 3060 90 120 180 240 300 min
16
17. Dysglycaemia of Diabetes
Vascular complications in diabetes are mainly or partly dependent
on dysglycaemia
2 components:
• Sustained chronic hyperglycaemia
• Acute glucose fluctuations
Both component lead to diabetes complication through:
• Excessive protein glycation
• Activation of oxidative stress
Monnier L et al. J Diabetes Sci Technol 2008;2:1094-1100 17
18. Glycaemic variability
Glycaemic variability – an important parameter
used to resolve potential clinical problems in
diabetic patients
Acts as independent risk factor for diabetic
complications, although HbA1c values were
intensely treated
Zaccardi F et al. J Diabetes Sci Technol 2008;2:1061-5 18
19. Glucose variability: Should we prevent it?
Activation
of
oxidative
stress
FPG
PPG HbA1c
(glycation)
Acute glucose
fluctuations
(MAGE)
Adapted from Monnier L, Colette C. Diabetes Care 2008;31(Suppl2):S150-4
Correlated with
urinary excretion rate
of 8-iso-PGF2α
Reflects the level of
FPG and PPG
↑ production of
free radicals
Proportional to
magnitude of PPG
excursion
↑ formation
and urinary
excretion
rate of 8-iso-
PGF2α
Significantly
higher in
T2DM
(p<0.01)
8-iso-PGF2α is a parameter of activation of oxidative stress
19
20. Glucose Tetrad Concept
Glucose fluctuations and activation of oxidative stress contribute to
progression of vascular complications
Monnier L et all. Diabetes Metab Res Rev 2009;25:393-402 20
21. MAGE
Simple arithmetic average of the “amplitudes” of all glycaemic excursions
Amplitudes can be estimated by the magnitude of either the upward shifts
or the downward shifts of each excursion
• Upward excursion: MAGE+
• Inward excursion: MAGE-
• Average excursion: MAGE.avge
Baghurst PA. Diabetes Technol Ther 2011;13:296-301 Example of final MAGE calculation
22. 2 main advantages of MAGE
• The parameter is not dependent on the mean
glucose value
• It is designed to quantitate major glucose swings
and exclude minor ones
Monnier L et al. J Diabetes Sci Technol 2008;2:1094-1100 22
23. OPTIMA study: Vildagliptin vs. Sitagliptin
Vildagliptin provides 24-hours better glucose fluctuation control
Guerci B et al. Diabetes Metab 2012;38:359-66 23
24. OPTIMA study: Vildagliptin vs. Sitagliptin
917 872
1139
958
0
400
800
1200
Vildagliptin Sitagliptin
Baseline Week 8
Vildagliptin provide 24-hours better glucose fluctuation control and give
longer blood glucose ideal range significantly than Sitagliptin
Minutes
Adapted from Guerci B et al. Diabetes Metab 2012;38:359-66
Conclusion
Addition of DPP-4 inhibitor significantly reduced glycaemic variability with
no difference between the two drugs
However vildagliptin induced better circadian glycaemic control than
sitagliptin with a significant decrease on over all hyperglycaemia
Time takes to stay in ideal blood glucose range
24
25. Objective:
Evaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors,
sitagliptin and vildagliptin, known to have different efficacy on :
Mean amplitude of glycemic excursions (MAGE)
Oxidative stress
Systemic inflammatory markers in patients with type 2 diabetes
Rizzo MR et al. Diabetes Care 2012;35:2076-82 25
26. Design and Methods:
Prospective, randomized, open-label (PROBE) design (parallel group
with a blinded end point) in 90 patients with T2DM inadequately
controlled by metformin
The study assigned 45 patients to receive sitagliptin (100 mg once daily;
sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice
daily; vildagliptin group) for 12 weeks
MAGE, evaluated during 48 h of continuous subcutaneous glucose
monitoring (CSGM), allowed an assessment of daily glucose fluctuations
at baseline and after 12 weeks in all patients
Assessment of oxidative stress (nitrotyrosine) and systemic levels of
inflammatory markers interleukin (IL)-6 and IL-18 were performed at
baseline and after 12 weeks in all patients
Rizzo MR et al. Diabetes Care 2012;35:2076-82 26
27. Vildagliptin, compared to Sitagliptin, is significantly better in MAGE reduction,
hence better in reduction of oxidative stress
Rizzo MR et al. Diabetes Care 2012;35:2076-82
28. Conclusion:
MAGE reduction is associated with reduction of oxidative stress and
markers of systemic inflammation in type 2 diabetic patients.
These effects were greater in the vildagliptin group than in the sitagliptin
group
Rizzo MR et al. Diabetes Care 2012;35:2076-82 28
30. Vildagliptin and GLP-1 inactivation
• Vildagliptin 50 mg once daily: blocks GLP-1 inactivation during the
three daily meals, resulting in reduced PPG and its associated
reduction in FPG1
• Vildagliptin 50 mg twice daily: blocks GLP-1 inactivation over
24 hours, providing an additional reduction in FPG due to a direct
effect on overnight HGP1
• In moderate and severe renal impairment (RI):
‒ vildagliptin 50 mg once daily expected to block GLP-1 inactivation over
24 hours2
• reductions in HbA1c in patients with RI given qd dose comparable with bid
dose in similar patient population with preserved renal function and similar
baseline HbA1c2
qd=once daily; bid=twice daily
1Ahrén B, et al. Diabetes Obes Metab 2011;13:775–83; 2Lukashevich V et al. Diabetes Obes Metab 2011;13:947–54
30
32. 32
Europe
Austria, Belgium, Czech Republic, Germany, Greece, Netherlands,
Portugal, Slovakia, Sweden, Bulgaria, Luxembourg, Russia
Latin America
Mexico, Venezuela,
Argentina, Colombia,
Ecuador
Middle East
Jordan, Palestine, Lebanon,
Bahrain, Kuwait, Oman
United Arab Emirates
India
East Asia
South Korea
Philippines
27 Countries participating in EDGE
32
Total Enrolled Population: 45,868
Adapted from Mathieu C, et al. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2
diabetes: A real-life worldwide observational study (EDGE). Int J Clin Pract. 2013 Oct;67(10):947-56.
One of the largest T2DM observational studies ever conducted in a real-world setting
12-month observational, multicenter, post-authorisation, prospective cohort study, which included
45,868 patients from 27 countries worldwide
33. Overall HbA1c reductions Patients who achieved HbA1c <7%,
without hypoglycaemia and weight gain
The EDGE Study
35.1%
23.2%
0.0%
10.0%
20.0%
30.0%
40.0%
Vildagliptin Comparators
Patients at goal (HbA1c <7%)
-1.19
-0.99
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
Vildagliptin Comparators
HbA1c drop (%)
Vildagliptin n = 29759; Comparators n = 16078
BL 8.17% BL 8.16%
Adapted from Mathieu C, et al, Int J Clin Pract 2013;67:947-56
BL=baseline
OAD comparators used: metformin, SU, TZD, AGI, glinide; other DPP-4 inhibitors and GLP-1 analogues are
excluded
One of the largest T2DM observational studies ever conducted in a real-world setting
12-month observational, multicenter, post-authorisation, prospective cohort study, which included 45,868
patients from 27 countries worldwide
33
34. Vildagliptin as add-on metformin in real-life setting:
-1.1% HbA1c reduction
Broadly consistent with the decrease seen in randomized controlled trial settings
-1.19
-0.99
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
HbA1c change (%)
Vildagliptin
Comparator
Vildagliptin was consistently effective
in reducing HbA1c
12-month-therapy in real-life setting
(Baseline 8.17±1.3%)1
-0.7
-1.1
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
Vilda 50 mg qd
Vilda 50 mg bid
Vildagliptin as add-on metformin
24-week-therapy
in randomized controlled trial settings
(Baseline 8.4±0.1%)2
Consistent efficacy
1 EDGE Study. Mathieu C, et al, Int J Clin Pract 2013;67:947-56
2 Bosi E, et al, Diabetes Care 2007;30:890–5 34
35. EDGE study Conclusion
In conclusion, EDGE demonstrated in a real-life setting
that T2DM patients in whom second-line oral glucose-
lowering therapy is initiated:
• vildagliptin can succeed in lowering HbA1c to < 7%,
(without weight gain, hypoglycaemia or peripheral
oedema) in a higher proportion than comparator OADs
• No differences in the reported number of AEs or SAEs
between Vildagliptin and comparator OAD.
• This information is consistent with data from RCTs with
vildagliptin
35
36. 36
GUARD STUDY: data from >19,000 patients with T2DM
pooled from 4 different regions
Asia: Bangladesh; India; Pakistan; Philippines
Middle East: Bahrain; Kuwait; Lebanon; Oman; Qatar; UAE
Central America: Dominican Republic; El Salvador; Honduras; Panama
Africa: Egypt; Kenya; Nigeria; South Africa
T2DM=type 2 diabetes mellitus. Patients from Saudi Arabia were excluded from this analysis due to non-compliance with the study protocol.
Rosales et al. Poster 314 presented at the Australian Diabetes Society and the Australian Diabetes Educators Association Annual
Scientific Meeting, Melbourne, Australia, 27–29 August 2014.
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes Metab.
2015 Jan 14. doi: 10.1111/dom.12436 In press.
37. Adapted from Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes
Obes Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
Adapted from Rosales et al. Poster 314 presented at the Australian Diabetes Society and the Australian Diabetes Educators Association Annual
Scientific Meeting, Melbourne, Australia, 27–29 August 2014.
GUARD: prospective, multinational, ‘real-world’
study design
*As a free-dose combination or single-pill combination
Vildagliptin or vildagliptin add-on to metformin*
Data collection
(Visit 3)
Data collection
(Visit 2)
Data collection
(Visit 1)
Observational period of 24±6 weeks
Adult patients
with T2DM
Day 1 (baseline) Week 24 (final visit)Week 12
• Non-interventional study conducted under an umbrella protocol in four geographic regions
(Asia, Middle East, Africa and Central America)
‒ Treatments prescribed according to the physician’s judgment and clinical indication based on the
prescribing information in the respective countries, and was clearly separated from the decision to
include the patient in the study
‒ Only data from routine clinical practice collected
37
38. GUARD: significant reductions from baseline to Week 24 in
mean HbA1c
–1.29*
–1.17*
†At baseline, the mean overall HbA1c was 8.20 ± 0.88% (n=3,345) in the vildagliptin treatment group and 8.44 ± 0.85 (n=15,424) in the
vildagliptin plus metformin group.
BL, baseline; HbA1c, glycated haemoglobin; SD, standard deviation. Full analysis set, patients from vildagliptin and vildagliptin + metformin
treatment groups with a value for baseline HbA1c and at least one post-baseline HbA1c value available, last observation carried forward.
*p<0.0001 vs. baseline (twosided t-test)
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
MeanchangeinHbA1c
frombaseline(%)†
Vildagliptin Vildagliptin + metformin
0
–2
–4
0
–2
–4
n=3,216 n=14,807
38
39. GUARD: proportion of patients achieving target
HbA1c ≤7.0% at Week 24
47.2
0
20
40
60
80
100
42.8
0
20
40
60
80
100
Vildagliptin Vildagliptin + metformin
Proportionofpatientsat
targetHbA1c≤7.0%atWeek24(%)
HbA1c, glycated haemoglobin; Full analysis set, patients from vildagliptin and vildagliptin + metformin treatment groups with a value for
baseline HbA1c and at least one post baseline HbA1c value available, last observation carried forward
n=3,511 n=15,820
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
39
40. GUARD: significant reductions from baseline to Week 24 in
mean HbA1c across baseline HbA1c
Vildagliptin Vildagliptin + metformin
–3.06*
–0.81*
–1.89*
–1.26*
–3.30*
–0.84*
–1.30*
–1.84*
–1
–3
–5
–1
–3
–5
≤8 >8–9 >9–10 >10
BL HbA1c
category, %‡
MeanchangeinHbA1c
frombaseline(%)
Mean change in HbA1c at Week 24 according to baseline HbA1c level. Corresponding mean (SD) HbA1c values at baseline for vildagliptin group
respectively were:7.47, 8.51, 9.45, 11.40 and and vildagliptin added to metformin group were: 7.56, 8.54, 9.45, and 11.02.
BL, baseline; HbA1c, glycated haemoglobin. Full analysis set, patients from vildagliptin and vildagliptin + metformin treatment groups with a value for
baseline HbA1c and at least one post-baseline HbA1c value available, last observation carried forward. *p<0.0001 vs. baseline (twosided t-test).
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes Metab. 2015
Jan 14. doi: 10.1111/dom.12436 In press.
n=1,427 n=1,298 n=464 n=27 n=4,686 n=7,173 n=2,634 n=314
≤8 >8–9 >9–10 >10
–2
–4
00
–2
–4
40
41. GUARD: significant reductions from baseline to Week 24 in mean HbA1c
with vildagliptin monotherapy regardless of obesity status and age
MeanchangeinHbA1c
frombaseline(%)†
*P<0.0001 vs baseline (two-sided t-test). †At baseline, mean overall HbA1c was 8.21 ± 0.86% (non-obese; n=2,355) and 8.18 ± 0.94% (obese;
n=646); 8.22 ± 0.87% (aged <65 years; n=3,129) and 7.93 ± 1.01% (aged ≥65 years; n=187)
Full analysis set (consisting of all patients who provided informed consent and entered into the study); analysis conducted in patients with a value for
baseline (BL) HbA1c and at least one post-BL HbA1c value (if Week 24 value was missing, the last post-BL observation was carried forward).
BMI=body mass index
n=2,269 n=632
–1.16*
0
–1
–2
–3
–4
–1.27* –1.17*
0
–1
–2
–3
–4
–1.11*
n=3,016 n=174
Non-obese
BMI <30 kg/m2
Obese
BMI ≥30 kg/m2
Age
<65 years
Age
≥65 years
41Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
42. GUARD: significant reductions from baseline to Week 24 in mean HbA1c
with vildagliptin + metformin regardless of obesity status and age
MeanchangeinHbA1c
frombaseline(%)†
*P<0.0001 vs baseline (two-sided t-test). †At baseline, mean overall HbA1c was 8.43 ± 0.84% (non-obese; n=9,316) and 8.49 ± 0.88% (obese;
n=4,398); 8.45 ± 0.85% (aged <65 years; n=14,289) and 8.37 ± 0.96% (aged ≥65 years; n=1,007)
Full analysis set (consisting of all patients who provided informed consent and entered into the study); analysis conducted in patients with a value for
baseline (BL) haemoglobin A1c (HbA1c) and at least one post-BL HbA1c value (if Week 24 value was missing, the last post-BL observation was
carried forward). BMI=body mass index
Non-obese
BMI <30 kg/m2
Obese
BMI ≥30 kg/m2
Aged
<65 years
Aged
≥65 years
–1.26*
0
–1
–2
–3
–4
–1.41* –1.29*
0
–1
–2
–3
–4
–1.35*
n=13,751 n=953n=8,967 n=4,218
42Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
43. GUARD: changes in body weight and BMI from baseline to
Week 24
Meanchangeinbody
weightfrombaseline(kg) Vildagliptin Vildagliptin + metformin
–1.1*
–1.5*
Mean body weight and BMI at baseline: 75.7 kg and 27.4 kg/m2 for vildagliptin monotherapy; 78.6 kg and 28.5 kg/m2 for
vildagliptin + metformin.
• At Week 24, mean body mass index (BMI) decreased from baseline by 0.4 kg/m2 with vildagliptin
and 0.5 kg/m2 with vildagliptin + metformin (both P<0.0001 vs baseline)
0
–1
–2
–3
–4
0
–1
–2
–3
–4
Adapted from Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study.
Diabetes Obes Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
43
*P<0.0001 vs baseline
44. GUARD: AEs and SAEs
44
Vildagliptin
(n=3,511)
Vildagliptin + metformin
(n=15,820)
Total AEs, n (%)* 143 (4.1) 556 (3.5)
Hypoglycaemia† 12 (0.3) 55 (0.3)
Nausea 6 (0.2) 43 (0.3)
Diarrhoea 7 (0.2) 34 (0.2)
Gastritis 7 (0.2) 23 (0.1)
Urinary tract infection 6 (0.2) 22 (0.1)
Dyspepsia 10 (0.3) 16 (0.1)
Peripheral neuropathy 10 (0.3) 3 (0.0)
Total SAEs, n (%) 8 (0.2) 14 (0.1)
*Occurring in ≥0.2% of any treatment group; †The number of patients with HEs was greater when data were recorded on a specific reporting form (vildagliptin: n=18;
vildagliptin + metformin: n=78) versus AE records; the dedicated HE form is more likely to capture non-symptomatic HEs (based on blood glucose measurements) as
well as symptomatic HEs
Full analysis set (consisting of all patients who provided informed consent and entered into the study); analysis conducted in patients with a value for baseline
(BL) haemoglobin A1c (HbA1c) and at least one post-BL HbA1c value; AE=adverse event; HE=hypoglycaemic events; SAEs=serious adverse events
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
45. GUARD was a large prospective study assessing vildagliptin with/without
metformin in a real-world setting: more than 19,000 patients with T2DM were
pooled across Asia, Middle East, Central America and Africa
Vildagliptin with/without metformin was associated with statistically significant
and clinically relevant HbA1c reductions from baseline
This effect was observed irrespective of patient age or obesity status and was
seen across baseline HbA1c categories
Vildagliptin without/without metformin was generally well tolerated
Overall, the findings from the real-world GUARD study are generally consistent
with other real-world studies and interventional controlled clinical trials with
vildagliptin with/without metformin
GUARD study: conclusions
45
Rosales et al. 2015. Clinical effectiveness and safety of vildagliptin in >19,000 patients with type 2 diabetes: the GUARD study. Diabetes Obes
Metab. 2015 Jan 14. doi: 10.1111/dom.12436 In press.
46. Safety and Efficacy Profile in
T2DM Patiens With Moderate and
Severe Renal Impairment
47. Analysis of data from 102 prospective studies on diabetes morbidity and
mortality comparing those with and without diabetes in 698 782 pts
Rank Conditions Hazard
ratio
95% CI
1. Renal disease 3.02 2.39 – 3.82
2. Infection 2.39 1.95 – 2.93
3. Death from vascular causes 2.32 2.11 – 2.56
4. Coronary death 2.31 2.05 – 2.60
5. Liver disease 2.28 1.90 – 2.74
6. Ischemic stroke 2.27 1.95 – 2.65
7. Coronary heart disease 2.00 1.83 – 2.19
8. Mental disorder 1.64 1.45 – 1.92
9. Haemorrhagic stroke 1.56 1.19 – 1.61
10. Death from cancer 1.25 1.19 – 1.31
Sanwar N et al. Lancet 2010:2215-2222
Seshasai SR et al. N Engl J Med 2011: 829-841 47
48. Renal dysfunction is common in patients with type 2
diabetes mellitus
Russo E et al. Diabetes Metab Syndrome Obes Target Ther 2013;6:161-70
48
49. Considerations for management of T2DM in renal impairment
GLP-1 analogue (exenatide)2
Metformin2
Sulphonylurea (glimepiride)3,4
Pioglitazone5
DPP-4 inhibitors (e.g. saxagliptin, sitagliptin, vildagliptin, linagliptin)2
Repaglinide, Nateglinide6,7
Insulin2
Acarbose2
SGLT-2 inhibitor (dapagliflozin)1
1. SmPC: Forxiga 5 mg & 10 mg film coated tablets (dapagliflozin); 2. Russo et al. Diabetes Metab Syndr Obes 2013;6:161–70; 3. SmPC: glimepiride 2 mg
tablets; 4. Product monograph, Amaryl, September 2013; 5. SmPC: Actos tablets (pioglitazone); 6. SmPC: repaglinide 2 mg tablets and nateglinide 60/120 mg
tablets; 7. Yale. J Am Soc Nephrol 2005;16:S7–10
Renal function
Normal Mild RI Moderate Severe Terminal
GFR (mL/min) >90 60–90 <60 <30 <15
SGLT-2=sodium/glucose cotransporter 2
50. Is There Evidence of Any Safety Differences Among
DPP-4 inhibitors in Treatment of People with T2DM and
CKD?
• DPP-4 inhibitors have been shown to be associated with no further decline in
estimated glomerular filtration rate (eGFR) when treating patients with CKD
• Vildagliptin 50 mg efficacy is maintained when the frequency of dosing is reduced
from twice daily in patients with normal renal function to once daily in patients
with moderate or severe RI
• The dose adjustments thus require regular monitoring of renal function, which is
also good clinical practice because in these patients it is important to closely
monitor renal disease progression.
• Other than the specifications for modifications in dose or dose frequency, there
appears to be no difference between each DPP-4 inhibitor with respect to their
safety and tolerability in patients with T2DM and CKD
• Study in which vildagliptin was dosed at either 50 mg once or twice daily in
patients with ESRD, both dosing regimens were well tolerated, with no clinically
important differences noted between doses with respect to adverse events. Thus,
any concern that accumulation of vildagliptin (or its renally excreted metabolites)
results in an increase in renal or other toxicities is not supported by data.
Evans, et al, Diabetes Ther (2015) 6:1–5
51. Vildagliptin data in renal impairment
UACR=urinary albumin-to-creatinine ratio ; RI = renal impairment
The prescribing information may vary from country to country. Before prescribing, please refer to your local country’s full prescribing information for
locally approved indications and full details.. In general, no dose adjustment is required for vildagliptin in patients with mild renal impairment (creatinine
clearance ≥ 50 ml/min). In patients with moderate or severe renal impairment or with end-stage renal disease (ESRD), the recommended dose of
vildagliptin is 50 mg once daily. There is limited experience in patients with ESRD on haemodialysis and hence should be used with caution in these
patients
1. Tani S et al, Am J Cardiovasc Drugs 2013;13:443–450; 2. Banerji et al. Diabetes Res Clin Pract. 2010;90:182-90; 3. Novartis data on file;
4. Lukashevich et al. Diabetes Obes Metab 2011;13:947–54; 5. Kothny et al. Diabetes Obes Metab 2012;14:1032–9;
6. Lukashevich et al. Vasc Health Risk Manag 2013; 9:21–8; 7. Ito et al. Diabetes Ther 2013;4:321–9;
8. Haidinger et al. Am J Transplant 2014;14:115–23; 9. He et al. J Clin Pharmacol Ther 2013; 51:693–703
Mild Moderate Severe
Pharmacokinetic data in mild, moderate and severe RI9
UACR at 8
weeks1
Mild RI at 24
weeks3
Add-on to MET in
mild RI at 12 weeks2
Moderate RI
at 24 weeks4
Moderate RI
at 52 weeks5
Elderly
≥75 years
at 24 weeks3
Severe RI
at 24 weeks4
Add-on to
insulin at 24
weeks6
Severe RI
at 52 weeks5
52. Efficacious and well tolerated in T2DM patients with
MILD Renal Impairment
As well as patients with normal GFR
Vildagliptin 100 mg daily as monotheraphy
effectively lowers HbA1c
Meta analysis, ≥ 12-week duration, baseline HbA1c ≥
8.6%
Vildagliptin is well tolerated in patients
with normal GFR and mild Renal Impairment
Meta analysis, ≥ 12-week duration
Reference
Thuren T, et al, EASD 2008. Poster, 88
52
Active Comparator: metformin, pioglitazon, rosiglitazon
-1.1%
-1.0%
53. Stages of chronic kidney disease / guideline
Chronic kidney disease is defined as either kidney damage or GFR <60 mL/min/1.73m2 for
≥3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, including
abnormalities in blood or urine tests or imaging studies.
Stage Description
Currently accepted values
GFR (mL/min/1.73m2)^
1 Kidney damage with normal or ↑ GFR ≥90
2 Kidney damage with mild ↓ GFR 60–89
3 Moderate ↓ GFR 30–59
4 Severe ↓ GFR 15–29
5 Kidney failure <15 (or dialysis)
^National Kidney Foundation. KDOQI, Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification.
CKD, chronic kidney disease; GFR, glomerular filtration rate
Am J Kidney Dis 39:S1-S000, 2002 (suppl 1).
53
54. Pharmacokinetic parameters of Vildagliptin
in Various Renal Condition
Adapted from He YL et al. Int J Clin Pharmacol Ther. 2013; 51:693–703.
Parameter
HS
(n=46)
Mild RI
(n=16)
Controls
to mild RI
(n=16)
Moderate
RI
(n=16)
Controls to
moderate RI
(n=16)
Severe RI
(n=18)
Controls to
severe RI
(n=14)
Plasma
Cmax, ng/ml 251 (79) 326 (77) 245 (83) 343 (139) 258 (96) 361 (137) 253 (58)
tmax, h 1.5 (0.5, 3.0) 1.5 (0.5, 2.0) 1.5 (0.5, 3.0) 2.0 (0.5, 3.0) 1.5 (0.5, 3.0) 1.8 (1.0, 3.0) 1.5 (1.0, 2.0)
AUC0–24h, ng*h/ml 990 (237) 1323 (291) 954 (215) 1810 (688) 1038 (264) 2113 (1130) 980 (240)
t½, h 2.8 (2.1) 2.7 (1.2) 2.9 (2.2) 3.1 (1.0) 2.1 (0.6) 3.6 (1.3) 3.3 (2.9)
Data are mean (SD) unless specified otherwise.
Ae0-24h, amount of vildagliptin excreted in the urine during the interval of 0–24 hours, AUC0–24h, area under the plasma concentration time curve
from 0–24 hours, Cmax, maximum plasma concentration; CLR, renal clearance; CL/F, oral clearance; HS, healthy subjects; RI, renal imapirment;
t1/2, terminal elimination half-life; tmax, time to maximum plasma concentration. For tmax median (min, max) is presented.
Vildagliptin AUC increased on average 1.4, 1.7 and 2-fold in patients with mild, moderate and severe RI, respectively, compared with
normal healthy subjects.
AUC0–24h, ng*h/ml 990 (237) 1323 (291) 954 (215) 1810 (688) 1038 (264) 2113 (1130) 980 (240)
54
55. Conclusions
• The pharmacokinetic results from this study indicate that no dose adjustment for
vildagliptin is necessary in patients with mild RI (50 mg bid).
• In patients with moderate or severe RI, vildagliptin 50 mg qd is considered
appropriate and recommended.
bid, twice daily; qd, once daily; RI, renal impairment
He YL et al. Int J Clin Pharmacol Ther. 2013; 51:693–703.
55
56. Aim: To assess the effects of vildagliptin 50 mg qd in patients with advanced type 2 diabetes and
moderate or severe RI whose hyperglycemia was not adequately controlled with insulin alone or in
combination with an oral anti-diabetic agent at baseline.
Study design: This was a 24-week, multicenter, randomized, double-blind, parallel group, placebo-
controlled trial of vildagliptin in adult patients (age 18–85 years) with T2DM and moderate or severe RI
(eGFR by the MDRD formula ≥ 30 to <50 and <30 ml/min/1.73 m2, respectively).
Effecicay of Vildagliptin in MODERATE and
SEVERE Renal Disease
eGFR, estimated glomerular filtration rate; MDRD, modification of diet in renal disease; RI, renal impairment
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
Placebo + current therapy (N=226)
N=525
Vildagliptin 50 mg qd + current therapy (N=289)
Placebo run-in plus stable
dose of current therapy*
Period I Period II
24-week, double-blind treatment2 weeks
*Randomized patients must remain on their current anti-diabetic therapy (stable dose for at least 4 weeks prior to visit 1 or remain
untreated for the duration of the study if patient is not on anti-diabetic therapy at study entry (unless patient meets criteria for rescue
medication). Total of 525 includes 10 patients with mild RI revealed during re-classification by MDRD method: 7 were randomized to
vildagliptin, 3 to placebo, but data from mild RI patients are not reported.
Study design figure was prepared based on the data provided in the article
56
57. Patient demographics and background
characteristics were comparable at baseline
Mean ± SD or n (%)
Moderate RI patients Severe RI patients*
Vildagliptin 50 mg qd
(n=165)
Placebo
(n=129)
Vildagliptin 50 mg qd
(n=124)
Placebo
(n=97)
Age (years) 67.7 ± 8.8 69.7 ± 7.3 64.1 ± 9.2 64.5 ± 10.8
eGFR [MDRD (ml/min/1.732)] 39.3 ± 6.0 40.3 ± 5.8 21.9 ± 5.7 20.9 ± 6.4
Age group, n (%)
≥65 y 114 (69.1) 102 (79.1) 64 (51.6) 48 (49.5)
≥75 y 36 (21.8) 35 (27.1) 14 (11.3) 20 (20.6)
Gender, male 96 (58.2) 80 (62.0) 65 (52.4) 53 (54.6)
Race, n (%)
Europid 116 (70.3) 94 (72.9) 61 (49.2) 49 (50.4)
Asian (Indian subcontinent) 24 (14.5) 15 (11.6) 22 (17.7) 21 (21.6)
Asian (non-Indian subcontinent) 0 (0.0) 0 (0.0) 2 (1.6) 0 (0.0)
Hispanic or Latino 21 (12.7) 16 (12.4) 36 (29.0) 26 (26.8)
Black 2 (1.2) 0 (0.0) 2 (1.6) 0 (0.0)
Other 2 (1.2) 4 (3.1) 1 (0.8) 1 (1.0)
Mean BMI (kg/m2) 30.2 ± 5.1 30.0 ± 5.0 30.2 ± 5.6 29.5 ± 5.0
Mean HbA1c (%) 7.8 ± 1.0 7.8 ± 0.9 7.7 ± 1.0 7.7 ± 1.0
≤8.0%, n (%) 98 (59.4) 80 (62.0) 87 (70.2) 66 (68.0)
Mean FPG (mmol/l) 9.1 ± 3.3 8.4 ± 2.7 8.1 ± 2.8 8.6 ± 3.4
Mean duration of T2DM (years) 15.0 ± 9.1 15.2 ± 10.0 17.3 ± 8.6 19.0 ± 9.6
Randomized set. Demography and duration of T2DM was collected on day of screening (week -2). Baseline HbA1c and FPG were collected on
Day 1 or the sample obtained at an earlier visit closest to Day 1, if Day 1 measurement was missing. *Two patients in each group had end stage
renal disease. BMI, body mass index; GFR, glomerular filtration rate; T2DM, type 2 diabetes mellitus; RI, renal impairment
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
57
58. Concomitant anti-diabetic therapy at baseline
were comparable between treatment groups
Moderate RI patients Severe RI patients*
Vildagliptin 50 mg qd
(n=165)
Placebo
(n=129)
Vildagliptin 50 mg qd
(n=124)
Placebo
(n=97)
Current anti-diabetic therapy, n (%)
None 6 (3.6) 5 (3.9) 5 (4.0) 1 (1.0)
Any 159 (96.4) 124 (96.1) 119 (96.0) 96 (99.0)
Insulin monotherapy 95 (57.6) 68 (52.7) 87 (70.2) 66 (68.0)
Insulin & OAD 18 (10.9) 20 (15.5) 13 (10.5) 12 (12.4)
OAD monotherapy 39 (23.6) 33 (25.6) 18 (14.5) 14 (14.4)
OAD combination therapy 7 (4.2) 3 (2.3) 1 (0.8) 4 (4.1)
*Two patients in each group had end stage renal disease
OAD, oral anti-diabetic drug
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
58
59. Vildagliptin sustained HbA1c reduction over 24
weeks in both moderate and severe RI patients
RI, renal impairment
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
Time-course of mean HbA1c (±SE) during rescue-free treatment in patients with moderate or severe RI
6.7
6.9
7.1
7.3
7.5
7.7
7.9
8.1
-4 0 4 8 12 16 20 24MeanHbA1c(%)
Weeks of Treatment
Vildagliptin 50 mg qd
Placebo
Moderate RI patients Severe RI patients
6.7
6.9
7.1
7.3
7.5
7.7
7.9
8.1
-4 0 4 8 12 16 20 24
MeanHbA1c(%)
Weeks of Treatment
0
0
Moderate RI patients
59
60. Overall safety and tolerability of vildagliptin was similar to
placebo in moderate/severe RI patient
Event category, n (%)
Moderate RI patients Severe RI patients
Vildagliptin 50 mg
qd (n=163)
Placebo
(n=129)
Vildagliptin 50 mg
qd (n=124)
Placebo
(n=97)
Any adverse event 110 (67.5) 94 (72.9) 90 (72.6) 72 (74.2)
Any serious adverse event 15 (9.2) 11 (8.5) 23 (18.5) 20 (20.6)
Any adverse event leading to
discontinuation
4 (2.5) 7 (5.4) 11 (8.9) 6 (6.2)
Deaths* 1 (0.6) 1 (0.8) 3 (2.4) 4 (4.1)
*None of the deaths were suspected to be related to study drug. A patient with multiple occurrences of an adverse event under one treatment
is counted only once in the adverse event category for that treatment. RI, renal impairment
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
60
61. Incidences of common AEs (≥5%) were similar between
groups in moderate / severe RI patients
Preferred term, n (%)
(Common AEs ≥5% in any group)
Moderate RI patients Severe RI patients
Vildagliptin 50 mg qd
(n=163)
Placebo
(n=129)
Vildagliptin 50 mg qd
(n=124)
Placebo
(n=97)
Asthenia 9 (5.5) 6 (4.7) 7 (5.6) 6 (6.2)
Back pain 3 (1.8) 5 (3.9) 1 (0.8) 5 (5.2)
Blood glucose decreased 13 (8.0) 4 (3.1) 7 (5.6) 3 (3.1)
Diarrhea 8 (4.9) 5 (3.9) 11 (8.9) 8 (8.2)
Dizziness 14 (8.6) 14 (10.9) 12 (9.7) 10 (10.3)
Dyspnea 2 (1.2) 2 (1.6) 4 (3.2) 5 (5.2)
Fatigue 6 (3.7) 3 (2.3) 7 (5.6) 2 (2.1)
Hyperhidrosis 12 (7.4) 12 (9.3) 13 (10.5) 8 (8.2)
Hyperkalemia 4 (2.5) 4 (3.1) 13 (10.5) 4 (4.1)
Hypertension 3 (1.8) 3 (2.3) 6 (4.8) 9 (9.3)
Hyperuricemia 2 (1.2) 3 (2.3) 3 (2.4) 6 (6.2)
Hypoglycaemia 28 (17.2) 15 (11.6) 19 (15.3) 12 (12.4)
Influenza 4 (2.5) 2 (1.6) 8 (6.5) 1 (1.0)
Nasopharyngitis 9 (5.5) 13 (10.1) 4 (3.2) 5 (5.2)
Nausea 5 (3.1) 4 (3.1) 7 (5.6) 6 (6.2)
Edema, peripheral 18 (11.0) 13 (10.1) 21 (16.9) 18 (18.6)
Tremor 11 (6.7) 10 (7.8) 6 (4.8) 1 (1.0)
Urinary tract infection 5 (3.1) 5 (3.9) 6 (4.8) 5 (5.2)
Vomiting 0 (0.0) 4 (3.1) 7 (5.6) 4 (4.1)
A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. Coded using MedDRA version 13.1.
AE, adverse event; RI, renal impairment
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
61
62. Incidence of Hypoglycemia in T2DM Patient with
Moderate and severe RI receiving Vildagliptin
62
Adapted from Lukasevich V., et al, Diabetes, Obesity and Metabolism 13: 947–954, 2011
15.3% 15.6%
1.6%
12.4%
18.8%
2.1%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
18.0%
20.0%
HE HE in elderly ≥ 65
years
Severe
Hypoglycemia
Incidence of Hypoglycemic
Event in Severe RI
Vildagliptin 50 mg qd Placebo
The number of patients experiencing HE in moderate RI were 28 (17.2%) for vildagliptin and
15 (11.6%) for placebo. In the severe RI group, the number of patients experiencing HE was
19 (15.3%) for vildagliptin group and 12 (12.4%) for placebo.
RI = Renal Impairment, HE = Hypoglycemic Event
17.2%
11.5%
1.2%
11.6% 11.8%
1.6%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
18.0%
20.0%
HE HE in elderly ≥ 65
years old
Severe Hypoglycemia
Incidence of Hypoglycemic
Event in Moderate RI
Vildagliptin 50 mg qd Placebo
63. Vildagliptin is efficacious and well tolerated in
T2DM patients with MODERATE and SEVERE RI
-0.7
-0.9
-0.2
-0.3
-1
-0.8
-0.6
-0.4
-0.2
0
Vildagliptin
Placebo
Effectively reduced HbA1c
24-week treatment
67.5
72.672.9 74.2
60
65
70
75
Vildagliptin
Placebo
Proven good tolerability
24-week treatment
Any Serious Adverse Events (SAE’s) (%)
9.2
18.5
8.5
20.6
0
10
20
30
Vildagliptin
Placebo
Any Adverse Events (AE’s) (%)
Vildagliptin 50 mg qd, placebo qd
Moderate: eGFR ≥ 30 - < 50 ml/min/1.73 m2; severe Renal Impairment: eGFR < 30 ml/min/1.73 m2, RI = Renal Impairment
Adapted from Lukasevich V., et al, Diabetes, Obesity and Metabolism 13: 947–954, 2011
63
Moderate Severe
7.9% 7.8% 7.7% 7.7%Baseline
p<0.0001 vs. placebo
110 94 90 72
Moderate Severe
15 11 23 20
Moderate Severe
(n)
(n)
64. Conclusions
• Treatment with vildagliptin (50 mg qd) added to ongoing anti-diabetic therapy was
well-tolerated, with a safety profile comparable to placebo.
• In patients with moderate or severe RI, vildagliptin added to current therapy elicited
robust improvements in glycemic control with HbA1c reductions of ∼0.7% (from
baseline 7.9% in moderate RI) and ∼0.9% (from baseline of 7.7% in severe RI).
• It may be concluded that vildagliptin treatment is well-tolerated and effective in
patients with T2DM and moderate or severe RI and did not cause deterioration of
renal function.
RI, renal impairment; T2DM, type 2 diabetes mellitus
Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947–54.
64
65. Long-term Safety and Efficacy in Moderate
and Severe Renal Disease
● Aim: To assess long-term safety and efficacy of vildagliptin 50 mg qd in patients with T2DM and
moderate or severe RI.
● Design: This was a long-term extension of a randomized, double-blind, parallel-group, placebo-
controlled 24-week clinical trial. Adult patients (age 18–85 years) having T2DM and moderate or
severe RI (eGFR by the MDRD formula ≥ 30 to <50 mL/min/1.73 m2 and <30 mL/min/1.73 m2,
respectively) were included in this study.
N=515
Placebo + current therapy
(N=226)
Placebo + current therapy
(N=153)
Vildagliptin 50 mg qd +
current therapy (N=216)
Placebo run-in plus
stable dose of
current therapy*
2 weeks 24-week, double-blind treatment 28-week, double-blind treatment
Vildagliptin 50 mg qd +
current therapy (N=289)
Core Period I Core Period II Extension
Patients remained on their current anti-diabetic therapy or remained untreated for the duration of the study if patient was
not on anti-diabetic therapy at study entry (unless patient met criteria for rescue medication). Study design figure was
prepared based on the data provided in the article.
eGFR, estimated glomerular filtration rate; qd, once daily; RI, renal impairment; T2DM, type 2 diabetes mellitus
Kothny W et al. Diabetes Obes Metab. 2012; 14:1032–9.
65
66. Time-course of mean HbA1c (SE) during rescue-free treatment
in patients with moderate or severe RI
Vildagliptin maintained HbA1c reduction over 52 weeks in both
moderate and severe RI patients
6.8
7.2
7.6
8.0
8.4
-2 BL 4 8 12 16 20 24 40 52 EP
MeanHbA1c(%)
Time (week)
6.4
6.8
7.2
7.6
8.0
-2 BL 4 8 12 16 20 24 40 52 EP
MeanHbA1c(%)
Time (week)
Moderate RI patients Severe RI patients
Vildagliptin 50 mg qd
Placebo
Absolute mean change in HbA1c (%) from baseline to rescue-censored extension endpoint. Extension full analysis set. BL, baseline; EP, end point; RI, renal
impairment; SE, standard error
Kothny W et al. Diabetes Obes Metab. 2012; 14:1032–9.
66
67. Vildagliptin Has Comparable Safety Profile Compared to Placebo
Over 52 Weeks in T2DM patients with Moderate and Severe RI
Overall Summary
Moderate Severe
Vildagliptin
50 mg qd
(N=122) n (%)
Placebo
(N=89) n (%)
Vildagliptin
50 mg qd
(N=94) n (%)
Placebo
(N=64) n (%)
Any AE 103 (84.4) 76 (85.4) 80 (85.1) 56 (87.5)
Any suspected
drug-related AE
31 (25.4) 22 (24.7) 24 (25.5) 18 (28.1)
Any SAE 26 (21.3) 17 (19.1) 23 (24.5) 16 (25.0)
Any AE leading to
discontinuation
6 (4.9) 5 (5.6) 9 (9.6) 4 (6.3)
67
Kothny et al, Diabetes obes Metab 14: 1032-1039, 2012
68. Incidence of Hypoglycemia in T2DM Patient with
Moderate and severe RI receiving Vildagliptin
There was a slightly higher incidence of mild hypoglycaemia in patients with moderate RI treated with
vildagliptin than with placebo.
Rates of hypoglycaemia in patients with severe RI were similar across treatment groups.
Very few events of severe hypoglycaemia, and more with placebo than vildagliptin.
incidence of hypoglycaemia with vildagliptin in the present study (∼26% in patients with moderate RI and
∼18% in those with severe RI) appears to be lower than that expected (≥50%) in patients with
longstanding T2DM and low baseline A1C (∼7.6%).
68
26.2%
18.5%
1.6%
16.9% 17.1%
3.4%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
HE HE in elderly ≥ 65
years old
Severe
Hypoglycemia
Incidence of Hypoglycemic
Event in Moderate RI
Vildagliptin 50 mg qd Placebo
18.1%
15.6%
1.1%
17.2%
26.5%
4.7%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
HE HE in elderly ≥ 65
years old
Severe Hypoglycemia
Incidence of Hypoglycemic
Event in Severe RI
Vildagliptin 50 mg qd Placebo
Adapted from Kothny et al, Diabetes obes Metab 14: 1032-1039, 2012
The number of moderate RI patients experiencing HE in vildagliptin group is 32 (26.2%) , in placebo group 15 (16.9%) , with 2 patients
(1.6%) in vildagliptin group has severe Hypoglycemia and 3 (3.4%) in placebo group. In the severe RI patient, there are total of 17
(18.1%) patient experiencing HE in vildagliptin group and 11 (17.2%) patients in placebo group.
HE = Hypoglycemic event ; RI = Renal Impairment
69. Vildagliptin maintained HbA1c reduction over 52 weeks in
T2DM patients with moderate and severe RI
85.4
19.1
84.4
21.3
0
20
40
60
80
100
Placebo
Vildagliptin 50
mg OD
Safety Data In Moderate RI (%)
Safety Data In Severe RI (%)
87.5
25
85.1
24.5
0
50
100
Placebo
Vildagliptin 50
mg OD
-0.6
-0.2
-0.4
-0.8
-0.1
-0.7
-0.9
-0.8
-0.7
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0
Adjusted mean HbA1c change
from baseline in 52 weeks in patients with
moderate or severe Renal Impairment
Moderate
Severe
In patients with T2DM and moderate or severe Renal
Impairment, vildagliptin added to ongoing antidiabetic therapy
had a safety profile similar to placebo during 1-year
observation. Furthermore, relative to placebo, a clinically
significant decrease in A1C was maintained throughout 1-year
treatment with vildagliptin.
RI = Renal Impairment
Adapted from Kothny et al, Diabetes obes Metab 14: 1032-1039, 2012 69
103 76 26 17
Any AE Any SAE
(n)
(n)80 56 23 16
Any AE Any SAE
Vildagliptin Placebo Between Treatment
Difference
7.8 7.7 7.7 7.5
Baseline
*p=0.005 vs placebo; **p<0.0001 vs placebo
*
**
70. Conclusions
This is the largest long-term study with a DPP-4 inhibitor in patients with T2DM and
moderate or severe RI.
Vildagliptin maintained the robust efficacy throughout 52 weeks with HbA1c
reductions of ~0.6% and ~0.8% from baselines of 7.8% and 7.7% in moderate and
severe RI, respectively.
Safety profile of vildagliptin 50 mg qd was similar to placebo when added to anti-
diabetic therapy during 1-year observation.
The incidence of hypoglycemia with vildagliptin (26% in moderate and 19% severe RI
groups) was lower than expected in patients with longstanding T2DM receiving
insulin ± OADs and achieving significantly tighter glycemic control at low baseline
HbA1c (~7.6%). The risk of severe hypoglycemia was very low.
These data support the long-term safety and efficacy of vildagliptin 50 mg qd added
to ongoing anti-diabetic therapy in patients with moderate or severe RI.
OAD, oral anti-diabetes drug; qd, once daily; RI, renal impairment; T2DM, type 2 diabetes mellitus
Kothny W et al. Diabetes Obes Metab. 2012; 14:1032–9.
70
75. OPTIMA study: Vildagliptin vs. Sitagliptin
Vildagliptin provide 24-hours better glucose fluctuation control and give
longer blood glucose ideal range significantly than Sitagliptin
Guerci B et al. Diabetes Metab 2012;38:359-66