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
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.
This document discusses the challenges of managing diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD progression and that CKD increases mortality risk in diabetes patients. Managing glucose levels in CKD patients is difficult due to risks of hypoglycemia from insulin clearance issues and need to adjust oral medications for kidney function. The CARMELINA trial demonstrated the renal safety of the DPP-4 inhibitor linagliptin in high cardio-renal risk patients, showing no increase in sustained decrease in eGFR or other renal outcomes compared to placebo over 2 years.
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.
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
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.
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 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
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.
This document discusses the challenges of managing diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD progression and that CKD increases mortality risk in diabetes patients. Managing glucose levels in CKD patients is difficult due to risks of hypoglycemia from insulin clearance issues and need to adjust oral medications for kidney function. The CARMELINA trial demonstrated the renal safety of the DPP-4 inhibitor linagliptin in high cardio-renal risk patients, showing no increase in sustained decrease in eGFR or other renal outcomes compared to placebo over 2 years.
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.
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
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.
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 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
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
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
DPP4 inhibitors have similarities such as sustained glucose lowering, minimal side effects, and weight neutrality. Differences include binding characteristics, with some binding longer to DPP4. Vildagliptin may provide better fasting glucose control due to maintaining overnight GLP1 levels. Vildagliptin has proven efficacy and safety in Ramadan fasting and has shown cardiovascular safety in clinical trials and real-world evidence, with no increased risk of heart failure unlike some other DPP4 inhibitors.
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.
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.
Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of kidney disease progression, defined as an eGFR of 20-45 mL/min/1.73 m2 or an eGFR of 45-90 mL/min/1.73 m2 with albuminuria above 200 mg/g. Patients will be randomly assigned to receive empagliflozin 10 mg daily or placebo daily in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease,
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
This document summarizes key information about the drug Empagliflozin. It belongs to the sodium glucose co-transporter 2 inhibitor class, which works by inhibiting glucose reabsorption in the kidney and increasing glucose excretion. The document outlines Empagliflozin's pharmacodynamics, pharmacokinetics, adverse reactions, dosage and administration, current status, and references. It provides an overview of Empagliflozin's mechanism of action, metabolism, excretion, drug interactions, efficacy, safety profile, and approved uses as monotherapy or add-on therapy for type 2 diabetes.
This document discusses diabetic kidney disease (DKD). It provides information on the epidemiology, clinical presentation, pathogenesis, standard of care, and pharmacological interventions to reduce cardiorenal risk in patients with type 2 diabetes. Regarding standard of care, it outlines glycemic and blood pressure targets, the use of RAAS inhibitors and statins, and glucose-lowering medications. It then discusses how SGLT2 inhibitors have shown benefits in reducing cardiovascular, renal, and heart failure outcomes as well as slowing kidney disease progression in patients with DKD and type 2 diabetes.
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.
- 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
Achieving Treatment Outcome With DPP4i for Diabetic Patient "Efficacy Beyond ...Suharti Wairagya
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.
1) Several cardiovascular outcome trials (CVOTs) have evaluated the cardiovascular safety of various anti-hyperglycemic medications used to treat type 2 diabetes since 2008 FDA guidelines requiring such trials.
2) The trials found that GLP-1 agonists liraglutide and semaglutide reduced cardiovascular events, while DPP-4 inhibitors and sulfonylureas showed cardiovascular neutral results. SGLT2 inhibitors empaglifozin and canaglifozin reduced cardiovascular death and hospitalization for heart failure.
3) However, CVOTs have limitations such as lack of generalizability, short follow-up periods, and placebo-controlled designs, indicating a need for more
The SUSTAIN-6 trial evaluated the cardiovascular safety of the GLP-1 receptor agonist semaglutide compared to placebo in patients with type 2 diabetes at high risk of cardiovascular events. Over 3,000 patients were followed for a median of 2.1 years. The trial found that semaglutide was noninferior to placebo with respect to cardiovascular safety and reduced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke by 26% compared to placebo. Semaglutide also significantly reduced HbA1c, body weight, and systolic blood pressure.
This document summarizes recent developments with SGLT2 inhibitors. It discusses their use in non-diabetic heart failure and kidney disease, where trials have shown benefits. Potential additional uses discussed include NAFLD, obesity, sleep apnea, and PCOS, though evidence is limited. Risks are discussed for using SGLT2 inhibitors in type 1 diabetes or with very low carb diets. In conclusion, SGLT2 inhibitors have cardio-renal-metabolic effects but significant challenges remain in establishing their role for various non-standard conditions.
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.
Jardiance (empagliflozin) is an FDA-approved SGLT-2 inhibitor for the treatment of type 2 diabetes. It works by inhibiting SGLT2 in the kidney to increase glucose excretion. A 104-week randomized controlled trial found that Jardiance as an add-on to metformin was as effective as glimepiride in reducing A1C levels and had fewer side effects like weight gain and hypoglycemia. The study concluded that Jardiance can be considered as a second-line treatment for patients with uncontrolled diabetes on metformin, especially those who are obese or hypertensive. However, more research is still needed to fully understand its cardiovascular effects.
The document summarizes clinical trials evaluating SGLT2 inhibitors:
1) The EMPA-REG trial found that empagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure, and all-cause mortality compared to placebo in patients with type 2 diabetes at high cardiovascular risk.
2) The CANVAS trial found that canagliflozin reduced the risk of major adverse cardiovascular events and hospitalization for heart failure compared to placebo in patients with type 2 diabetes at high cardiovascular risk.
3) The DECLARE-TIMI 58 trial found that dapagliflozin did not increase the risk of major adverse cardiovascular events compared to placebo in patients with type 2 diabetes
This document discusses diabetes management in patients receiving dialysis for end-stage renal disease. It covers alterations in glucose metabolism caused by kidney dysfunction, limitations of monitoring glycemic control in dialysis patients, glycemic targets and outcomes, and safety of diabetic medications in this population. Treatment approaches discussed include insulin regimens, non-insulin agents like sulfonylureas and DPP-4 inhibitors, and unique considerations for peritoneal dialysis patients. Guidelines recommend A1c monitoring along with home glucose testing, though optimal glycemic targets in dialysis are unclear due to limited evidence.
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,
Presentation performed for highlighting VERIFY: Galvus-met trials superiority in managing newly diagnosed DMT2 patients with preserving B cell function, evidence.
DPP4 inhibitors have similarities such as sustained glucose lowering, minimal side effects, and weight neutrality. Differences include binding characteristics, with some binding longer to DPP4. Vildagliptin may provide better fasting glucose control due to maintaining overnight GLP1 levels. Vildagliptin has proven efficacy and safety in Ramadan fasting and has shown cardiovascular safety in clinical trials and real-world evidence, with no increased risk of heart failure unlike some other DPP4 inhibitors.
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.
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.
Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of kidney disease progression, defined as an eGFR of 20-45 mL/min/1.73 m2 or an eGFR of 45-90 mL/min/1.73 m2 with albuminuria above 200 mg/g. Patients will be randomly assigned to receive empagliflozin 10 mg daily or placebo daily in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease,
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
This document summarizes key information about the drug Empagliflozin. It belongs to the sodium glucose co-transporter 2 inhibitor class, which works by inhibiting glucose reabsorption in the kidney and increasing glucose excretion. The document outlines Empagliflozin's pharmacodynamics, pharmacokinetics, adverse reactions, dosage and administration, current status, and references. It provides an overview of Empagliflozin's mechanism of action, metabolism, excretion, drug interactions, efficacy, safety profile, and approved uses as monotherapy or add-on therapy for type 2 diabetes.
This document discusses diabetic kidney disease (DKD). It provides information on the epidemiology, clinical presentation, pathogenesis, standard of care, and pharmacological interventions to reduce cardiorenal risk in patients with type 2 diabetes. Regarding standard of care, it outlines glycemic and blood pressure targets, the use of RAAS inhibitors and statins, and glucose-lowering medications. It then discusses how SGLT2 inhibitors have shown benefits in reducing cardiovascular, renal, and heart failure outcomes as well as slowing kidney disease progression in patients with DKD and type 2 diabetes.
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.
- 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
Achieving Treatment Outcome With DPP4i for Diabetic Patient "Efficacy Beyond ...Suharti Wairagya
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.
1) Several cardiovascular outcome trials (CVOTs) have evaluated the cardiovascular safety of various anti-hyperglycemic medications used to treat type 2 diabetes since 2008 FDA guidelines requiring such trials.
2) The trials found that GLP-1 agonists liraglutide and semaglutide reduced cardiovascular events, while DPP-4 inhibitors and sulfonylureas showed cardiovascular neutral results. SGLT2 inhibitors empaglifozin and canaglifozin reduced cardiovascular death and hospitalization for heart failure.
3) However, CVOTs have limitations such as lack of generalizability, short follow-up periods, and placebo-controlled designs, indicating a need for more
The SUSTAIN-6 trial evaluated the cardiovascular safety of the GLP-1 receptor agonist semaglutide compared to placebo in patients with type 2 diabetes at high risk of cardiovascular events. Over 3,000 patients were followed for a median of 2.1 years. The trial found that semaglutide was noninferior to placebo with respect to cardiovascular safety and reduced the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke by 26% compared to placebo. Semaglutide also significantly reduced HbA1c, body weight, and systolic blood pressure.
This document summarizes recent developments with SGLT2 inhibitors. It discusses their use in non-diabetic heart failure and kidney disease, where trials have shown benefits. Potential additional uses discussed include NAFLD, obesity, sleep apnea, and PCOS, though evidence is limited. Risks are discussed for using SGLT2 inhibitors in type 1 diabetes or with very low carb diets. In conclusion, SGLT2 inhibitors have cardio-renal-metabolic effects but significant challenges remain in establishing their role for various non-standard conditions.
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.
Jardiance (empagliflozin) is an FDA-approved SGLT-2 inhibitor for the treatment of type 2 diabetes. It works by inhibiting SGLT2 in the kidney to increase glucose excretion. A 104-week randomized controlled trial found that Jardiance as an add-on to metformin was as effective as glimepiride in reducing A1C levels and had fewer side effects like weight gain and hypoglycemia. The study concluded that Jardiance can be considered as a second-line treatment for patients with uncontrolled diabetes on metformin, especially those who are obese or hypertensive. However, more research is still needed to fully understand its cardiovascular effects.
The document summarizes clinical trials evaluating SGLT2 inhibitors:
1) The EMPA-REG trial found that empagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure, and all-cause mortality compared to placebo in patients with type 2 diabetes at high cardiovascular risk.
2) The CANVAS trial found that canagliflozin reduced the risk of major adverse cardiovascular events and hospitalization for heart failure compared to placebo in patients with type 2 diabetes at high cardiovascular risk.
3) The DECLARE-TIMI 58 trial found that dapagliflozin did not increase the risk of major adverse cardiovascular events compared to placebo in patients with type 2 diabetes
This document discusses diabetes management in patients receiving dialysis for end-stage renal disease. It covers alterations in glucose metabolism caused by kidney dysfunction, limitations of monitoring glycemic control in dialysis patients, glycemic targets and outcomes, and safety of diabetic medications in this population. Treatment approaches discussed include insulin regimens, non-insulin agents like sulfonylureas and DPP-4 inhibitors, and unique considerations for peritoneal dialysis patients. Guidelines recommend A1c monitoring along with home glucose testing, though optimal glycemic targets in dialysis are unclear due to limited evidence.
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,
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.
Dapagliflozin demonstrated clear treatment benefits for cardiovascular, kidney, and mortality outcomes in patients with chronic kidney disease (CKD), regardless of the presence of diabetes. It provides glomerular protection, limits proteinuria and kidney damage, and slows the decline of glomerular filtration rate in CKD patients. The DAPA-CKD trial found that dapagliflozin reduced the risk of end-stage renal disease or death from renal causes compared to placebo in CKD patients with and without type 2 diabetes. Dapagliflozin is indicated for the treatment of CKD up to stage III and was well tolerated with a low rate of treatment discontinuation.
Diabetic kidney disease remains a major global health problem. Recent research has provided insights into the pathophysiology and has identified new diagnostic and therapeutic approaches. Several large clinical trials have shown that sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and endothelin receptor antagonists can reduce kidney disease progression and cardiovascular events in patients with diabetes and kidney disease. Ongoing trials are further evaluating combination therapies and the benefits of these agents in non-diabetic kidney disease and heart failure.
- Type 2 diabetes is associated with increased risk of cardiovascular disease. Up to 80% of patients with diabetes develop macrovascular disease.
- Guidelines from the ADA and EASD recommend early use of combination therapies to control blood sugar levels tightly and avoid clinical inertia.
- Saxagliptin/Metformin fixed dose combination is recommended as it provides 24-hour glycemic control with once daily dosing through complementary mechanisms of action without increasing hypoglycemia risk. It has shown sustained efficacy over 4 years in clinical trials.
This document discusses the challenges of treating diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD and end-stage renal disease. While good glycemic control can prevent CKD progression, it is difficult to achieve in CKD patients due to changes in insulin metabolism and increased risk of hypoglycemia. The document reviews various classes of anti-diabetic medications and their safety in different stages of CKD. It concludes that treatment options are limited for patients with more advanced CKD and emphasizes individualizing therapy based on renal function.
This document discusses new-onset diabetes after transplantation (NODAT), which occurs in some patients after receiving a solid organ transplant. It defines NODAT and reviews its epidemiology and risk factors. The document outlines the pathogenesis and risk of NODAT associated with different immunosuppressive drugs. It also discusses the diagnosis, screening, and management of NODAT, including monitoring patients, treating hyperglycemia, and controlling cardiovascular risk factors. The document notes ongoing areas of uncertainty around preventing NODAT and determining the long-term impacts of improved glycemic control.
This document discusses the potential benefits of combining a SGLT-2 inhibitor (SGLT2i) and DPP-4 inhibitor (DPP4i) for treatment of type 2 diabetes. It notes that SGLT2is increase glucagon levels while DPP4is inhibit glucagon release, providing a counteracting effect. The combination addresses multiple metabolic abnormalities and has synergistic effects on glycemic control, cardiovascular risk reduction, renal protection, and other benefits. Clinical evidence suggests this combination may be preferred over other therapies for patients with diabetes and cardiovascular or renal complications.
This document discusses diabetes mellitus and its management. It provides information on:
1) The classification and prevalence of diabetes in Saudi Arabia, finding an overall prevalence of 23.7% with higher rates in males.
2) The diagnostic criteria and thresholds for diabetes based on HbA1c, fasting plasma glucose, and oral glucose tolerance tests. Screening is recommended for those over 45 or with risk factors.
3) Treatment involves lifestyle modifications, metformin as first line therapy, and additional oral medications or insulin as needed to achieve glycemic targets. Managing associated cardiovascular risk factors is also emphasized.
Diabetic nephropathy is a clinical syndrome characterized by the following :
Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least 2 occasions 3-6 months apart.
Progressive decline in the glomerular filtration rate (GFR).
Elevated arterial blood pressure.
Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy:
First, mesangial expansion is directly induced by hyperglycemia, perhaps via increased matrix production or glycation of matrix proteins.
Second, thickening of the glomerular basement membrane (GBM) occurs.
Third, glomerular sclerosis caused by intraglomerular hypertension (induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli).
These different histologic patterns appear to have similar prognostic significance.
Several issues are key in the medical care of patients with diabetic nephropathy.
These include glycemic control, management of hypertension, and reducing dietary salt intake and phosphorus and potassium restriction in advanced cases.
A meta-analysis from the Cochrane Database shows a large fall in blood pressure with salt restriction, similar to that of single-drug therapy
Imeglmin Slides agents in Types 2 Diabetes Mellitusameetrathod4
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Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
Facebook: https://www.facebook.com/doc.usama
Facebook Clinic: https://www.facebook.com/usamaclinic
Mobile: 00201000035863
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The use of vildagliptin in patients with type 2 diabetes with renal impairment
1. The use of vildagliptin
in patients with type 2
diabetes with renal
impairment
Dr. Usama Ragab Youssif, MD
Lecturer of Medicine
Zagazig University
ISMA CME Series – Toilp Elgalala – Elsokhna
16 June 2022 – 5.30 PM
Contact: Dr. Usama Ragab Youssif
00201000035863
usamaragab@medicine.zu.edu.eg
Slideshare: dr4spring
2. 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
• Issue of glycemic variability: vildagliptin versus comparator
• Final bottom-line
3. Case
• Mr X. 60-year-old man with a 15-year
history of T2DM has a HbA1c of 8.7%.
• He has been referred by his PCP to
discuss management of his diabetes.
• He is taking glibenclamide at 5 mg twice
daily and metformin at 1,000 mg twice
daily along with candesartan and
atorvastatin.
4. Case (cont.)
• On examination his BMI is 29
kg/m2, his BP is 150/90 mm
Hg, and he has evidence of
peripheral neuropathy.
• He has an eGFR of 33
mL/min/m2 and a urinary ACR
of 317 mg/g.
5. Case (cont.)
• He developed episodes of
hypoglycemia, now he was
told by his physician that he
has no longer diabetes
• He stopped his medications
7. Diabetes and CKD
Kidney disease is a frequent diabetic complication
‒ Type 1 diabetes ~30%
‒ Type 2 diabetes ~40%
Diabetes is the most common cause of CKD and ESRD in the
developed and developing worlds
‒ Diabetes prevalence in US ESRD patients: 66%-86%
depending on race
Diabetic kidney disease amplifies CVD risk
‒ Much of diabetes-associated excess CVD risk occurs in
diabetic kidney disease
National Kidney Foundation. https://www.kidney.org/atoz/content/diabetes
11. People with diabetes 6-12X more likely to be hospitalized for
CKD or End-stage renal disease
Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada).
15. 3- Choice of treatment
https://doi.org/10.1016/j.kint.2020.06.019
16. Rational of treating diabetes in CKD
You are treating diabetes → reducing albuminuria →
reducing CKD
The benefits of intensive glycemic control must be
balanced against the potential harm i.e., hypo and drug AE
Hypoglycemia may occur = may be a sign that CKD has
progressed.
37. Overall summary of adverse events by treatment and severity of renal impairment
Diabetes, Obesity and Metabolism 14: 1032–1039, 2012
38. Hypoglycemic
events was
less in
vildagliptin
treated arm
• The incidence of hypoglycemia with vildagliptin
in this study (26% in patients with moderate renal
impairment and 18% in those with severe renal
failure) appears to be lower than the one expected
(<50%) in patients with long-standing T2DM and
low baseline HbA1c receiving insulin with or
without OADs.
40. • The most likely mechanistic
explanation for vildagliptin's
protective effect is increased
GIP-mediated stimulation of
glucagon release in response to
initial plasma glucose reduction.
58. Recommended dose adjustment for DPP4i patients with CKD
Abe, Masanori, and Kazuyoshi Okada. Chronic kidney diseases-recent advances in clinical and basic research 185 (2015): 98-115
61. Problem
• There is increasing evidence
that glycemic disorders such as
rapid glucose fluctuations over a
daily period might play an
important role on diabetic
complications
62.
63. Study Design
• The efficacy of sitagliptin 100 mg once daily vs.
vildagliptin 50 mg twice daily on daily blood
glucose fluctuations in patients with type 2
diabetes that was inadequately controlled by
metformin
• Number: 38
• Duration: 3 months
64. Procedure
• 48-hour CGM was performed in patients treated
with metformin plus vildagliptin (n=18) or sitagliptin
(n=20) over a period of 3 months.
• The mean amplitude of glycemic excursions
(MAGE) was used for assessing glucose fluctuations
during the day.
• During a standardized meal, glucagon-like peptide-
1 (GLP-1), glucagon, and insulin were measured.
65. Vildagliptin
• Although similar
in DPP-4 inhibition,
the differences in
PK profiles may
induce a different
activity over day
Journal of Diabetes and Its Complications 24 (2010) 79–83
66. Inter-prandial
plasma GLP-1
• Significant higher level of inter-prandial plasma
GLP-1 levels following 3 month compared to
sitagliptin
Journal of Diabetes and Its Complications 24 (2010) 79–83
67. Significant more inter-prandial plasma glucagon suppression levels
following 3 months compared to sitagliptin
Journal of Diabetes and Its Complications 24 (2010) 79–83
68. Vildagliptin showed
significant reduction in
glucose fluctuation,
MAGE, by 51 %
compared with
Sitagliptin... Hence
reduces oxidative
stress... Reduces free
radical... Less
complications
Journal of Diabetes and Its Complications 24 (2010) 79–83
69. Final Bottom-line
• Vildagliptin could be used in any degree of renal impairment if used according to product labeling
• Fit in any renal scenario
• Safety similar to placebo
• Less glycemic fluctuation
70. In CKD with diabetes
“after utilizing
nephroprotective
SGLT2i” there is no
treatment of choice,
rather there is choice of
treatment
Evidence that intensive glycemic control reduces the kidney complications of diabetes is based almost exclusively on prevention of micro- and macro-albuminuria.
The risk for hypoglycemia may increase as CKD progresses.
Circulating levels of insulin are higher due to reduced catabolism by the kidneys.
Insulin prescription may be reduced.
Oral medications may change.
Discuss importance of notifying healthcare team of any increase in hypoglycemia with the patient.
In a double-blind, randomized, parallel-group, 52-week clinical trial with 369 patient of T2DM and moderate or severe Renal impairment for comparing safety and efficacy of vildagliptin (50mg qd, n= 216) and placebo (n= 153) when added to ongoing stable antihyperglycaemic treatment, Kothny et al demonstrated that vildagliptin in addition to on going antihyperglycemic therapy had a safety profile similar to placebo during 1-year observation with a clinically significant and consistent decrease in A1C throughout 1-year with vildagliptin treatment.
In summary, this is the largest long-term experience with a DPP-4 inhibitor reported thus far in patients with T2DM and moderate or severe RI.
Treatment with vildagliptin (50 mg qd) added to ongoing antidiabetic therapy was well tolerated, with a safety profile comparable to placebo. Key findings for the clinician are that the robust improvements in glycaemic control seen after 24 weeks were maintained at 52 weeks, with A1C reductions of ∼0.6% (from a baseline of 7.8% in moderate RI and ∼0.8% (from a baseline 7.8% in severe RI), and that the long-term safety data continue to support vildagliptin safety in this vulnerable patient population, with no new safety signals identified.
The effect of vildagliptin in T2DM patients with ESRD on hemodialysis has been directly assessed in a 24-week, prospective, open-label, controlled study.
Vildagliptin, given to 30 patients at 50–100 mg/day, decreased HbA1c levels from 6.7% to 6.1%. Consensually, postprandial plasma glucose decreased from 186 to 140 mg/dL in the absence of serious AEs such as severe hypoglycemia or liver impairment. Although long-term follow-up of these patients is necessary to confirm this efficacy, vildagliptin could be considered as an alternative to insulin in patients on hemodialysis. Long-term observation is also advisable with respect to safety. Very recently, two cases of pancreatitis associated with incretin-based therapies in ESRD patients undergoing dialysis have been reported: a 75-year-old woman with a history of liraglutide use and a 68-year-old man on vildagliptin.36 Whether, ESRD may represent a condition at high risk for pancreatitis remains to be elucidated.
New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation, but therapeutic strategies remain underexplored.Dipeptidyl peptidase-4 (DPP-4) inhibitors selectively foster insulin secretion without inducing hypoglycemia, which might be advantageous in kidney transplant recipients (KTRs) with NODAT. We conducted a randomized, double-blind, placebo-controlled, phase II trial to assess safety and efficacy of the DPP-4 inhibitor vildagliptin. Intraindividual differences in oral glucose tolerance test (OGTT)-derived 2-h plasma glucose (2HPG) from baseline to 3 months after treatment served as primary endpoint. Among secondary outcomes, we evaluated HbA1c, metabolic and safety parameters, as well as OGTTs at 1 month after drug discontinuation. Of 509 stable KTRs who were screened in our outpatient clinic, 63 (12.4%) had 2HPG 200 mg/dL, 33 of them were randomized and 32 completed the study. In the vildagliptin group 2HPG and HbA1c were profoundly reduced in comparison to placebo (vildagliptin: 2HPG ¼ 182.7 mg/dL, HbA1c ¼ 6.1%; placebo: 2HPG ¼ 231.2 mg/dL, HbA1c ¼ 6.5%; both p 0.05), and statistical significance was achieved for the primary endpoint (vildagliptin: 2HPG-difference 73.7 51.3 mg/dL; placebo: 5.7 41.4 mg/dL; p < 0.01). Adverse events were generally mild and occurred at similar rates in both groups. In conclusion, DPP-4 inhibition in KTRs with overt NODAT was safe and efficient, providing a novel treatment alternative for this specific form of diabetes.
We were able to demonstrate that the DPP-4 inhibitor vildagliptin was highly efficient in achieving adequate glycemic control after short-term treatment.
Furthermore, vildagliptin was expectably safe regarding hypoglycemic episodes. Adverse events were mild and appeared at similar rates in both study arms. Thus, vildagliptin proved to be a safe and efficient treatment option against NODAT in KTRs, and provides a suitable alternative for this specific form of diabetes.
Although similar in DPP-4 inhibition, the differences in pharmacokinetic profiles may induce a different activity over a daily period:
Plasma DPP-4 activity is inhibited by almost 100% already at 15–30 min, and 80% inhibition lasts for almost 14 h after a single dose of sitagliptin at 100 mg
Vildagliptin at 50 mg bid inhibits DPP- 4 activity by almost 97% over a 24 hrs period
Plasma DPP-4 activity is inhibited by almost 100% already at 15–30 min, and 80% inhibition lasts for almost 14 h after a single dose of sitagliptin at 100 mg
Vildagliptin at 50 mg bid inhibits DPP- 4 activity by almost 97% over a 24 hrs period
This data suggests that the DPP-4 inhibition therapy should target not only reducing HbA1c, PPG, and mean hyperglycemia but also flattening acute glucose fluctuations over a daily period
When administered according to the product labelling, vildagliptin is an effective and well tolerated therapy choice for individuals with type 2 diabetes mellitus, including those with any degree of renal impairment.
Patients with advanced type 2 diabetes and poor renal function who require insulin therapy and present a severe therapeutic challenge in clinical practice may benefit from vildagliptin.
From my opinion, in CKD with diabetes “after utilizing nephroprotective SGLT2i” there is no treatment of choice, rather there is choice of treatment