This document discusses the management of type 2 diabetes with a focus on glimepiride. It provides information on:
1) Glimepiride's mechanism of action in stimulating insulin secretion from pancreatic beta cells and increasing insulin sensitivity in tissues, addressing both causes of hyperglycemia.
2) Evidence that glimepiride is effective at controlling blood glucose both as a monotherapy and in combination with other drugs or insulin, with studies showing its ability to lower A1C levels over 18 months and reduce insulin requirements when used with insulin.
3) Benefits of glimepiride including controlling glycemia with less insulin secretion compared to other sulfonylureas, improving treatment adherence through once daily dos
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
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.
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.
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 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.
Recent Advances in Obesity PharmacotherapyShreya Gupta
This document summarizes recent advances in obesity, including potential new drug targets. It discusses drugs currently in development like tesofensine, setmelanotide, semaglutide, and velneperitide that act on targets such as serotonin-norepinephrine-dopamine reuptake, melanocortin receptors, GLP-1 receptors, and neuropeptide Y receptors. The document also mentions exploring cannabinoid type 1 receptor blockers with limited brain penetration to avoid the psychiatric side effects that led to previous drugs being withdrawn.
The document discusses acarbose, an oral medication for type 2 diabetes. It provides background on the development of diabetes treatments over time and criteria for diagnosing diabetes. It then focuses on acarbose, explaining that it works by inhibiting enzymes involved in breaking down carbohydrates, which reduces the rise in blood glucose after meals. Studies show acarbose can help lower HbA1c levels and may reduce cardiovascular risks when used long-term for people with type 2 diabetes or prediabetes. Common side effects include flatulence, diarrhea, and abdominal pain.
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
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.
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.
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 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.
Recent Advances in Obesity PharmacotherapyShreya Gupta
This document summarizes recent advances in obesity, including potential new drug targets. It discusses drugs currently in development like tesofensine, setmelanotide, semaglutide, and velneperitide that act on targets such as serotonin-norepinephrine-dopamine reuptake, melanocortin receptors, GLP-1 receptors, and neuropeptide Y receptors. The document also mentions exploring cannabinoid type 1 receptor blockers with limited brain penetration to avoid the psychiatric side effects that led to previous drugs being withdrawn.
The document discusses acarbose, an oral medication for type 2 diabetes. It provides background on the development of diabetes treatments over time and criteria for diagnosing diabetes. It then focuses on acarbose, explaining that it works by inhibiting enzymes involved in breaking down carbohydrates, which reduces the rise in blood glucose after meals. Studies show acarbose can help lower HbA1c levels and may reduce cardiovascular risks when used long-term for people with type 2 diabetes or prediabetes. Common side effects include flatulence, diarrhea, and abdominal pain.
The document discusses various aspects of metformin, including:
- Metformin's mechanisms of action involve both direct and indirect activation of AMPK, leading to effects like decreased glucose, lipid, and protein synthesis.
- Studies have shown metformin may be associated with better cardiac outcomes compared to other glucose-lowering drugs and should not be withheld in patients with stable heart disease or heart failure.
- Infants exposed to metformin in utero had increased subscapular skinfolds but similar body fat compared to unexposed infants, potentially signaling healthier fat distribution.
- Metformin may lower B12 levels but does not necessarily cause deficiency if metabolic markers remain normal, as cellular B12 uptake may increase with metformin therapy
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
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
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.
- 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
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 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 SGLT2 inhibitors as a treatment option for type 2 diabetes mellitus. It provides background on normal glucose homeostasis and the pathophysiology of hyperglycemia in diabetes. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, causing it to be excreted in the urine. Clinical trial data shows SGLT2 inhibitors like dapagliflozin provide glycemic control as monotherapy or add-on therapy with other oral agents or insulin, with additional benefits of weight loss and blood pressure reduction. Long-term studies over 4 years show sustained glycemic control with dapagliflozin compared to other oral antidiabetic drugs.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
Imeglimin is a novel anti-diabetic drug that targets mitochondrial dysfunction, a key pathological basis for diabetes. It acts on the pancreas to preserve insulin secretion and on tissues to enhance insulin action. Imeglimin has shown efficacy in reducing HbA1c and fasting glucose when used alone or in combination with other drugs. It offers advantages over existing treatments by improving mitochondrial function without inhibiting respiration and has shown protective effects on organs like the kidney and heart. The risk of lactic acidosis may be lower compared to metformin due to distinct mechanisms of action.
incretin based therapy of type 2 diabetes mellitus 1SoM
This document discusses the pathophysiology of type 2 diabetes and new therapies based on incretin hormones. It describes how both insulin resistance and relative insulin deficiency contribute to diabetes due to impaired beta cell function. Incretin hormones like GLP-1 enhance insulin secretion and reduce glucagon levels, but are broken down quickly. New therapies include incretin mimetics like exenatide that are resistant to breakdown and have the added benefit of weight loss. DPP-IV inhibitors allow the body's own GLP-1 to remain active for longer by preventing its breakdown, and are weight neutral oral therapies like sitagliptin and vildagliptin that have few side effects. These new incretin based therapies improve
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.
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.
1. The diabtologist wished for an oral hypoglycemic agent that controls blood glucose without hypoglycemia.
2. He wished for it to be used as a first line drug or added to other commonly used drugs like metformin or insulin.
3. He wished for it to have significant cardiovascular benefits and minimal side effects.
4. The genie granted these wishes by presenting dapagliflozin, an SGLT2 inhibitor that meets all the criteria wished for.
Anti-Diabetics For Cardiac Patients The Proper Selectionmagdy elmasry
Cardiovascular Disease and Type 2 Diabetes.Tight glycaemic control can reduce microvascular complications of T2DM, but does not lower CV risk sufficiently.
Multifactorial intervention, comprising of lowering lipid levels and BP, and use of aspirin, has been shown to reduce vascular complications and mortality.Shifting the Paradigm in Diabetes Care
Treating Diabetes Beyond A1C :Considerations for Cardiovascular Protection.
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 information about GLP-1 receptor agonists for treating diabetes. It reviews the pharmacology and mechanism of action of GLP-1 receptor agonists, comparing the advantages and disadvantages of the class. Specific products are discussed, including dosing and side effects. Head-to-head clinical trials comparing different GLP-1 receptor agonists are summarized. Safety issues like the black box warning for thyroid cancer risk are also addressed. The document provides an overview of GLP-1 receptor agonists for non-insulin treatment of diabetes.
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
Glimepiride is an effective second-generation sulfonylurea for treating type 2 diabetes that offers several advantages over other sulfonylureas. It is more specific to pancreatic beta cells, improving both first and second phase insulin secretion. It also has extrapancreatic glucose-lowering effects and a longer duration of action from once-daily dosing. Glimepiride has a favorable safety profile with fewer side effects like hypoglycemia compared to other sulfonylureas.
Sulfonylureas are oral hypoglycemic drugs that enhance insulin secretion from the pancreas. They work by blocking ATP-sensitive potassium channels in pancreatic beta cells, which leads to insulin release. Common side effects include hypoglycemia and weight gain. Examples include glibenclamide, glipizide, and glimepiride. Choice of sulfonylurea depends on factors like duration of action, renal function, and patient age. They are generally effective treatments for type 2 diabetes but require caution in elderly patients or those with kidney/liver problems.
The document discusses various aspects of metformin, including:
- Metformin's mechanisms of action involve both direct and indirect activation of AMPK, leading to effects like decreased glucose, lipid, and protein synthesis.
- Studies have shown metformin may be associated with better cardiac outcomes compared to other glucose-lowering drugs and should not be withheld in patients with stable heart disease or heart failure.
- Infants exposed to metformin in utero had increased subscapular skinfolds but similar body fat compared to unexposed infants, potentially signaling healthier fat distribution.
- Metformin may lower B12 levels but does not necessarily cause deficiency if metabolic markers remain normal, as cellular B12 uptake may increase with metformin therapy
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
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
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.
- 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
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 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 SGLT2 inhibitors as a treatment option for type 2 diabetes mellitus. It provides background on normal glucose homeostasis and the pathophysiology of hyperglycemia in diabetes. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, causing it to be excreted in the urine. Clinical trial data shows SGLT2 inhibitors like dapagliflozin provide glycemic control as monotherapy or add-on therapy with other oral agents or insulin, with additional benefits of weight loss and blood pressure reduction. Long-term studies over 4 years show sustained glycemic control with dapagliflozin compared to other oral antidiabetic drugs.
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
Imeglimin is a novel anti-diabetic drug that targets mitochondrial dysfunction, a key pathological basis for diabetes. It acts on the pancreas to preserve insulin secretion and on tissues to enhance insulin action. Imeglimin has shown efficacy in reducing HbA1c and fasting glucose when used alone or in combination with other drugs. It offers advantages over existing treatments by improving mitochondrial function without inhibiting respiration and has shown protective effects on organs like the kidney and heart. The risk of lactic acidosis may be lower compared to metformin due to distinct mechanisms of action.
incretin based therapy of type 2 diabetes mellitus 1SoM
This document discusses the pathophysiology of type 2 diabetes and new therapies based on incretin hormones. It describes how both insulin resistance and relative insulin deficiency contribute to diabetes due to impaired beta cell function. Incretin hormones like GLP-1 enhance insulin secretion and reduce glucagon levels, but are broken down quickly. New therapies include incretin mimetics like exenatide that are resistant to breakdown and have the added benefit of weight loss. DPP-IV inhibitors allow the body's own GLP-1 to remain active for longer by preventing its breakdown, and are weight neutral oral therapies like sitagliptin and vildagliptin that have few side effects. These new incretin based therapies improve
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.
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.
1. The diabtologist wished for an oral hypoglycemic agent that controls blood glucose without hypoglycemia.
2. He wished for it to be used as a first line drug or added to other commonly used drugs like metformin or insulin.
3. He wished for it to have significant cardiovascular benefits and minimal side effects.
4. The genie granted these wishes by presenting dapagliflozin, an SGLT2 inhibitor that meets all the criteria wished for.
Anti-Diabetics For Cardiac Patients The Proper Selectionmagdy elmasry
Cardiovascular Disease and Type 2 Diabetes.Tight glycaemic control can reduce microvascular complications of T2DM, but does not lower CV risk sufficiently.
Multifactorial intervention, comprising of lowering lipid levels and BP, and use of aspirin, has been shown to reduce vascular complications and mortality.Shifting the Paradigm in Diabetes Care
Treating Diabetes Beyond A1C :Considerations for Cardiovascular Protection.
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 information about GLP-1 receptor agonists for treating diabetes. It reviews the pharmacology and mechanism of action of GLP-1 receptor agonists, comparing the advantages and disadvantages of the class. Specific products are discussed, including dosing and side effects. Head-to-head clinical trials comparing different GLP-1 receptor agonists are summarized. Safety issues like the black box warning for thyroid cancer risk are also addressed. The document provides an overview of GLP-1 receptor agonists for non-insulin treatment of diabetes.
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
Glimepiride is an effective second-generation sulfonylurea for treating type 2 diabetes that offers several advantages over other sulfonylureas. It is more specific to pancreatic beta cells, improving both first and second phase insulin secretion. It also has extrapancreatic glucose-lowering effects and a longer duration of action from once-daily dosing. Glimepiride has a favorable safety profile with fewer side effects like hypoglycemia compared to other sulfonylureas.
Sulfonylureas are oral hypoglycemic drugs that enhance insulin secretion from the pancreas. They work by blocking ATP-sensitive potassium channels in pancreatic beta cells, which leads to insulin release. Common side effects include hypoglycemia and weight gain. Examples include glibenclamide, glipizide, and glimepiride. Choice of sulfonylurea depends on factors like duration of action, renal function, and patient age. They are generally effective treatments for type 2 diabetes but require caution in elderly patients or those with kidney/liver problems.
This document summarizes a review of medications for treating type 2 diabetes. It finds that metformin, sulfonylureas, thiazolidinediones, and other medications can lower HbA1c by about 1 percentage point. Two-drug combinations may lower HbA1c more than monotherapies. Metformin is associated with less weight gain and more favorable lipid effects compared to other medications. Sulfonylureas and meglitinides may cause more hypoglycemia while metformin causes more gastrointestinal side effects. There is insufficient evidence on long-term outcomes like mortality and complications. More research is needed comparing newer medications and combinations.
This document discusses insulin therapy for diabetes. It begins with a brief history of insulin's discovery in 1921 by Banting and Best in Toronto. It then covers normal insulin secretion patterns and the types of insulin available, including rapid-acting, short-acting, intermediate-acting, premixed, basal, and extended long-acting analog insulins. The document discusses initiating and titrating insulin using the ADA treatment algorithm, beginning with basal insulin and adding bolus insulin as needed based on blood glucose levels and HbA1c targets. It also covers starting and adjusting premixed insulin doses.
Glimepride is an oral anti-diabetic drug that is effective for treating type 2 diabetes through its unique dual mode of action. It improves insulin secretion from pancreatic beta cells and reduces insulin resistance in tissues. Studies show glimepride significantly lowers HbA1c, fasting plasma glucose, and postprandial glucose when used as monotherapy or in combination with other agents. It has a favorable safety profile with a lower risk of hypoglycemia and no weight gain compared to other sulfonylureas. Glimepride provides glycemic control throughout the day with convenient once daily dosing.
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
This document summarizes different types of anti-diabetic agents used to treat diabetes mellitus. It describes insulin and how it is synthesized, stored and secreted in the body. It also discusses oral anti-diabetic agents including insulin secretagogues, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors; and how each group works to lower blood glucose levels. Complications from insulin therapy and factors affecting insulin absorption are also summarized.
The document discusses metformin, an insulin-sensitizing drug that is the first-line treatment for polycystic ovary syndrome (PCOS). Metformin reduces insulin levels, restores ovulation and fertility in women with PCOS, and results in weight loss. A clinical trial found that metformin led to resumption of ovulation and menses in most women with PCOS and significantly more pregnancies than placebo. Metformin is thus an effective first-line treatment for restoring fertility and ovulation in women with PCOS.
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 discusses treatment options for type 2 diabetes after metformin therapy. It presents three case studies of patients with varying durations and levels of diabetes. It then outlines two general approaches to diabetes treatment: a guideline approach that advocates sequential addition of agents, and a pathophysiologic approach that uses initial combination therapy to address underlying defects. Key considerations for choosing therapies are discussed, such as efficacy, risk of hypoglycemia, weight gain, costs, and addressing patients with high baseline A1c levels. The advantages and disadvantages of various drug classes like sulfonylureas, glitazones, alpha-glucosidase inhibitors, and DPP-4 inhibitors are outlined.
Newer drugs approved by US-FDA - Rxvichu!!!RxVichuZ
This is my 22nd ppt............................
It contains HALF of the totl drugs approved by US-FDA for 2014
Consists of 20 drugs...out of 41
Do go through it.....and send ur reviews!
Regards,
Rxvichu-alwz4uh!
:)
This is a 16 slide presentation covering the the classes of drugs used in T2DM and their molecular mechanisms of action. Provided by Professor John A Peters, University of Dundee.
Several studies have compared basal-bolus insulin regimens using basal insulin plus oral agents to premixed insulin regimens in patients with type 2 diabetes:
- Studies found basal-bolus regimens were more effective at achieving glycemic targets and reducing HbA1c levels compared to premixed regimens.
- Basal-bolus regimens resulted in less hypoglycemia and weight gain.
- Physicians and patients reported greater treatment satisfaction with basal-bolus regimens due to their increased flexibility compared to fixed-ratio premixed regimens.
Human Mixtard is a premixed human insulin produced by Novo Nordisk for the treatment of diabetes mellitus. It contains a mix of regular insulin and NPH insulin in either a 30:70 or 50:50 ratio. Novo Nordisk is a global leader in the diabetes segment and is the only company that offers all types of insulin, including regular, NPH, premixed, long-acting detemir, and rapid-acting aspart varieties. Human Mixtard is available as vials and in pen devices.
1) Gliptins like vildagliptin have less risk of hypoglycemia and weight gain compared to sulfonylureas.
2) Vildagliptin has shown beneficial effects on blood pressure and lipid levels.
3) Meta-analyses of clinical trials show that gliptins like vildagliptin have no increased cardiovascular risk compared to other antidiabetic drugs, and may have cardio-protective effects.
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
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This meeting covered new developments in long-acting insulins, SGLT-2 inhibitors, and GLP-1 agonists. For long-acting insulins, insulin degludec and U300 glargine were discussed as having smoother profiles and less hypoglycemia than glargine. Canagliflozin, dapagliflozin, and empagliflozin were reviewed as the main SGLT-2 inhibitors, noting their A1c and weight lowering along with risks like ketoacidosis. Byetta, Victoza, Bydureon, Tanzeum, and Trulicity were the GLP-1 agonists summarized for their mechanisms, efficacy
This document summarizes a study comparing the use of glyburide versus insulin for the treatment of gestational diabetes. The study found that glyburide was as effective as insulin at controlling blood glucose levels and resulted in similar perinatal outcomes. Glyburide does not cross the placental barrier, so it does not pose risks of teratogenicity or neonatal hypoglycemia. While more research is still needed, the study shows promise for using glyburide as a safer alternative to insulin for treating gestational diabetes.
This document discusses the holistic approach to treatment of type 2 diabetes mellitus (T2DM). The objectives of T2DM treatment are to correct hyperglycemia, prevent acute complications, prevent chronic complications like retinopathy and nephropathy, and improve quality of life. Chronic complications are caused by microvascular and macrovascular damage. Intensive control of blood glucose, blood pressure, cholesterol and other risk factors can help prevent cardiovascular disease and mortality according to studies like STENO-2 and UKPDS. Treatment should be individualized based on factors like age, weight, comorbidities. Drugs like SGLT2 inhibitors and GLP-1 receptor agonists that provide cardiovascular protection are preferred. Metformin
Ueda 2016 5-pharmacological management of diabetes - lobna el toonyueda2015
Pharmacological management of diabetes involves approaches to treating type 2 diabetes, including glycemic control through oral antidiabetic drugs and insulin therapy. Insulin therapy is indicated for type 1 diabetes and can be used in type 2 diabetes when oral agents fail to control blood sugar levels. Basal insulin alone is often the initial insulin regimen but multiple daily injections or combined injectable regimens may be needed if blood sugar targets are not met. Insulin provides effective blood sugar control and is essential for treating diabetes in some patients.
Type 2 diabetes results from insulin resistance and inadequate insulin secretion. It is characterized by hyperglycemia and increases the risk of microvascular and macrovascular complications if poorly controlled. Treatment involves lifestyle modifications and medications to control blood glucose levels and prevent complications. The goals are to eliminate symptoms, prevent complications, and achieve an A1C under 7%. First line treatment is often metformin, while additional drugs may be added if goals are not met.
Ueda2016 symposium -managing t2 dm with no compromise - khaled el hadidyueda2015
This document discusses managing type 2 diabetes mellitus (T2DM) without compromise. It begins by describing the multiple pathophysiological failures that contribute to hyperglycemia in T2DM, known as the "ominous octet". It then notes that decreasing HbA1c is associated with increased risks of hypoglycemia and weight gain. The consequences of hypoglycemia are also outlined. Guidelines for T2DM treatment recommend early and tight management to control hyperglycemia and avoid complications. The benefits of early combination therapy over stepwise monotherapy are discussed.
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.
The document provides information on the management of type 2 diabetes mellitus (T2DM), including pathophysiology, treatment approaches, medication options, and treatment targets. It discusses lifestyle modifications and progressive medication options starting with metformin and including DPP-4 inhibitors, SGLT-2 inhibitors, thiazolidinediones, GLP-1 receptor agonists, and insulin. It also presents a case study example and discusses treatment considerations and options based on the patient's profile and treatment goals.
Synovia Modern Sulfonylurea Facts and Myths.pptxDrprince7
1. Sulfonylureas, particularly glimepiride, remain commonly used oral antidiabetic drugs in many Asian countries.
2. Glimepiride has been shown to effectively lower HbA1c levels and improve both first and second phase insulin secretion compared to other sulfonylureas.
3. Recent cardiovascular outcome trials have shown no increase in cardiovascular risk for modern sulfonylureas like glimepiride compared to other antidiabetic drugs.
Definition of diabetes - introduction - classification of diabetes - etiology of diabetes type 1 and type 2- risk factors for diabetes - diagnosis of diabetes - clinical manifestations of diabetes type 1 and type 2- investigations for diabetes - treatment of diabetes - non-pharmacological treatment and pharmacological treatment - pharmacotherapy of type 1 and type 2 - acute complications of diabetes and treatment
This document summarizes type 2 diabetes, including its pathophysiology, signs and symptoms, diagnosis, management goals, and treatment approaches. Type 2 diabetes is characterized by hyperglycemia due to insulin resistance and inadequate insulin secretion. Diagnosis is based on elevated blood glucose levels. Treatment goals are to reduce risks of microvascular and macrovascular complications through control of glycemia, blood pressure, lipids, and other factors. Common drug treatments include metformin, sulfonylureas, and other classes that work to lower blood glucose levels by various mechanisms. Lifestyle modifications and ongoing monitoring are also important for management.
Modern Modalities for Management of Diabetes Dr Mahir Jallo Gulf Medical Univ...Mahir Khalil Ibrahim Jallo
This document discusses modern modalities for managing diabetes. It begins with an overview of the different types of diabetes, including type 1, type 2, and gestational diabetes. It then discusses diabetes complications, both microvascular complications that affect small blood vessels, and macrovascular complications that affect larger blood vessels. The document notes that up to 80% of adults with diabetes will die of cardiovascular disease. It examines reasons for the increasing epidemic of diabetes, including physical inactivity, diet, aging populations, and urbanization. The rest of the document discusses various treatment options and medications for managing blood glucose levels in type 2 diabetes.
This document outlines a product plan for Galvus, a DPP-4 inhibitor for treating diabetes. It discusses the disease prevalence and burden of diabetes worldwide and in Pakistan. The document reviews the pharmacology and mechanism of action of Galvus in increasing incretin hormones and improving glycemic control. The vision is for Galvus to become the leader in the anti-diabetic market. An action plan is provided to target key customer segments and physicians to grow market share for Galvus.
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 guidelines for initiating basal insulin therapy in patients with type 2 diabetes, including benefits such as lowering HbA1c and reducing cardiovascular risk.
2) It compares different basal insulin options like glargine, detemir, and NPH insulin, finding that the long-acting analogs glargine and detemir have advantages like lower rates of hypoglycemia and weight gain compared to NPH.
3) Studies show that early initiation of basal insulin can help preserve beta-cell function and provide better long-term glycemic control for patients with type 2 diabetes.
This document discusses the benefits of early initiation of basal insulin in managing type 2 diabetes. It recommends starting with low doses of long-acting basal insulin, which can help lower HbA1c and reduce complications by providing consistent insulin levels throughout the day. Basal insulin is preferred over premix insulins when first adding insulin. Clinical guidelines support initiating basal insulin when oral medications fail to control blood sugar levels. Studies show basal insulin improves beta-cell function and glycemic control long-term compared to late insulin initiation.
This document discusses the underlying pathophysiology of type 2 diabetes, specifically insulin resistance and beta-cell dysfunction. It provides evidence that these defects are core features of type 2 diabetes and addressing them through treatments targeting insulin resistance can help improve diabetes care and outcomes. The document recommends understanding and treating the underlying pathophysiology, including insulin resistance, in order to better manage type 2 diabetes and reduce complications.
- 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.
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 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.
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Ueda2016 workshop - hypoglycemia1 -lobna el toonyueda2015
This document discusses hypoglycemia in diabetes. It defines hypoglycemia and describes its prevalence, causes, and risk factors. It notes that hypoglycemia is more common in type 1 diabetes and with intensive diabetes control. The document outlines the symptoms of mild, moderate, and severe hypoglycemia and explains how the body normally protects against low blood sugar. However, in diabetes these protective mechanisms become impaired over time, increasing the risk of severe hypoglycemia. The document discusses hypoglycemia in the context of type 1 and type 2 diabetes and provides tips for prevention and management, including recognizing risk factors, treating the underlying cause, and adjusting medications and food intake. It focuses on strategies to prevent nocturnal hypoglycemia specifically
Ueda2016 new horizon in the management of dyslipidemia - diaa ewaisueda2015
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2) Clinical trials of the PCSK9 inhibitors evolocumab and alirocumab showed reductions of LDL cholesterol up to 60-70% and reduced cardiovascular events.
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Ueda2016 woman’s health & diabetes - lobna el toonyueda2015
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Ueda2016 metabolic syndrome in different population,which one is appropriate ...ueda2015
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2. The Importance of Tight Glycemic
Control
Stratton IM, et al. BMJ 2000; 321: 405-412
Every 1% of HbA1c is important in the reduction of risk in
patients with type 2 diabetes (UKPDS)
Relative risk
(n=3642)
Diabetes-related death
Fatal and nonfatal
myocardial infarction
Microvascular
complications
Amputations or death
caused by peripheral
vascular disorders
Per 1% HbA1c
reduction
1%
p<0.001
21%
14%
37%
43%
3. Healthy eating, weight control, increased physical activity & diabetes education
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
high
low risk
gain
edema, HF, fxs
low
Thiazolidine-
dione
intermediate
low risk
neutral
rare
high
DPP-4
inhibitor
highest
high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-
dione
+
SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-ior
or
or GLP-1-RA
high
low risk
loss
GI
high
GLP-1 receptor
agonist
Sulfonylurea
high
moderate risk
gain
hypoglycemia
low
SGLT2
inhibitor
intermediate
low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor
agonist
+
SGLT-2
Inhibitor
+
SU
TZD
Insulin§
Metformin
+
Metformin
+
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono-
therapy
Efficacy*
Hypo risk
Weight
Side effects
Costs
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
Triple
therapy
or
or
DPP-4
Inhibitor
+
SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable
therapy‡
GLP-1-RAMealtime Insulin
Insulin (basal)
+
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
HbA1c
≥9%
Metformin
intolerance or
contraindication
Uncontrolled
hyperglycemia
(catabolic features,
BG ≥300-350 mg/dl,
HbA1c ≥10-12%)
4. Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update to a Position Statement of the AmericanDiabetes Association (ADA)
and the European Association for the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
5. Approach to management
of hyperglycemia: more
stringent
less
stringent
Patient attitude and
expected treatment efforts
highly motivated, adherent,
excellent self-care capacities
less motivated, non-adherent,
poor self-care capacities
Risks potentially associated
with hypoglycemia, other
adverse events
low high
Disease duration newly diagnosed long-standing
Life expectancy long short
Important comorbidities absent severefew / mild
Established vascular
complications
absent severefew / mild
Resources, support system readily available limited
Figure 1 Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
(Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)
6. Initial drug
monotherapy
Efficacy (! HbA1c)
Hypoglycemia
Weight
Side effects
Costs
Healthy eating, weight control, increased physical activity
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Efficacy (! HbA1c)
Hypoglycemia
Weight
Major side effect(s)
Costs
high
low risk
gain
edema, HF,fx’s‡
high
Thiazolidine-
dione
intermediate
low risk
neutral
rare‡
high
DPP-4
Inhibitor
highest
high risk
gain
hypoglycemia‡
variable
Insulin (usually
basal)
Two drug
combinations*
Sulfonylurea†
+
Thiazolidine-
dione
+
DPP-4
Inhibitor
+
GLP-1 receptor
agonist
+
Insulin (usually
basal)
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months,
proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin#
(multiple daily doses)
Three drug
combinations
More complex
insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high
low risk
loss
GI‡
high
GLP-1 receptor
agonist
Sulfonylurea†
high
moderate risk
gain
hypoglycemia‡
low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination
(order not meant to denote any specific preference):
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination
(order not meant to denote any specific preference):
Adapted Recommendations: When Goal is to Minimize Costs
Diabetes Care, Diabetologia. 19 April 2012
[Epub ahead of print]
9. K+
K+
GlimepirideGlibenclamide
Solubilisation
Glibenclamide Glimepiride
65 kDa
140 kDa
65 kDa
140 kDa
cell membrane
Sulfonylurea
receptor
Potassium channels
Glimepiride binds to the 65 kDa subunit of the sulfonylurea receptor;
glibenclamide binds to the 140 kDa subunit
Kramer W et al., Biochim Biophys Acta 1994;1191: 278-290
Hypothetical Model of Sulfonylurea
Receptor in -cells
10. 1st Action
Pancreatic : Insulin Secretion
• Glimepiride binds and dissociates rapidly to a different receptor than other
sulfonylureas[1,2]
e
e
Ca2+
[Ca2+]
Pancreatic B-cell
v
v
v
v
v
v
v v
K+ + ATP
KATP-channel
Insulin
secretion
SULFONYLUREASulfonylureas bind SUR1
receptors on β-cells
Close ATP-sensitive
K+ channels
Increased Ca2+ influx
Insulin-containing secretory
granules translocate to cell
surface
Insulin release[2]
1Kramer W, et al. Biochimica etl Biophysica Acta 1994; 1191: 278-290; 2Rosak C. J Diabetes Complications 2002;16:123-32
Glimepiride binds to SURx
Receptors on β-cells
Glimepiride
11. Acting on Both Phases of Insulin
Secretion
Glimepiride: The only sulfonylurea to treat
fasting and postprandial hyperglycemia
First Phase Second Phase
Insulin secretion
Before treatment After Glimepiride treatment
Incrementalplasmainsulin
(pmol/L)
0
50
100
p=0.04
First and second phase insulin secretion
before and after treatment with Glimepiride
p=0.02
+Glimepiride
+Glimepiride
Korytkowski M et al. Diabetes Care 2002; 25(9):1607-11.
Euglycemic and
hyperglycemic clamp
studies in 11 obese
patients with T2DM
with good glycemic
control before and after
4 months treatment
with Glimepiride to
assess effect of
Glimepiride on insulin
secretion
12. Glimepiride Controls Glycemia with
Less Insulin Secretion
• For an equivalent glycemic effect, Glimepiride induces a lower
secretion of insulin
Mean variation of insulin and
glycemia over a 36-h period
Mean ratio between increased level
of insulin and reduced glycemia
5
10
15
0
1
2
3
Glimepiride Glibenclamide Gliclazide Glipizide
20
0
Glycemic
variation(%)
Insulinemia
(U/mL)
GlimepirideGlibenclamide Glipizide Gliclazide
0.00
0.05
0.10
0.15
0.20
n=16
n=13
n=14
n=16
Ratio
Muller G, et al. Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37
Sulfonylureas tested in
fasted male beagle
dogs to determine
ratios of mean plasma
insulin release/ blood
glucose decrease
13. 1Müller & Wied. Diabetes. 1993;42: 1852-1867; 2Mori et al. Diabetes Obes Metab 200; epub ahead of print
The extrapancreatic effect of Glimepiride
Rate limiting step for glucose utilization is
glucose uptake via GLUT4 transporter
Glimepiride ↑ translocation of GLUT4
transporters from low-density microsomes
to plasma membrane
of insulin-resistant fat and muscle cells1
Glimepiride ↑ GLUT4 protein and glucose
utilization in oxidative muscles in vivo2
Glimepiride appears to ↑ peripheral
glucose uptake1,2 and to mimic
the action of insulin1
2nd Action
Extra-Pancreatic: Insulin Resistance
14. Glimepiride reduces Insulin Resistance
Inukai K, et al. Diabetes Res Clin Pract 2005; 68: 250-257
0
1
2
3
4
5
HOMA-IR
6
6.5
7
7.5
8
HbA1c (%)
Baseline 6 months
Gliclazide or
glibenclamide
(n=52)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
*
* *
Mean homeostasis model of insulin resistance (HOMA-IR) and
HbA1c (%) levels at baseline and after 6 months of treatment
*p< 0.05 vs baseline
Glimepiride maintains glycemic control and improves insulin sensitivity in
patients switching from gliclazide or glibenclamide
Gliclazide or
glibenclamide
(n=52)
Multicentre study in 172
Japanese patients in
whom glycemia was
inadequately controlled
(HbA1c ≥7%) by
gliclazide or
glibenclamide. Patients
were randomly assigned
to continue their usual
sulfonylurea or switch to
Glimepiride and were
followed for 6 months.
Baseline HbA1c: 7.5%
gliclazide/glibenclamide
; 7.6% Glimepiride
16. Glimepiride Sustained Glycemic Control
Mean change in HbA1c from baseline
HbA1c(%)
4 months 12 months 18 months
-1.4*
-1.5*
-1.7*
*p<0.0001
Weitgasser R, et al. Diabetes Res Clin Pract 2003; 61(1): 13-9
0
-0.2
-0.4
-0.8
-1.0
-1.2
-1.4
-1.6
-1.8
>1%
sustained
reduction
in HbA1c
1% reduction in
HbA1c means 37%
reduction in risk of
microvascular
complications,
according to UKPDS
study
Open-label study in 284 T2DM patients treated with
Glimepiride 0.5 to > 4 mg once daily for 1.5 years;
baseline HbA1c 8.4%
17. Efficacy: Glimepiride + Insulin
Combination• Reduced insulin requirement and faster glycemic control and with insulin +
Glimepiride vs insulin + placebo
Randomized, double-
blind, 24-week study in
T2DM subjects with
body weight >130%
ideal and in
secondary
sulfonylurea failure.
Patients were
randomized to
placebo + insulin or
Glimepiride + insulin.
Riddle et al. Diabetes Care 1998;21:1052-1057
* p<0.001; † p<0.05 vs Glimepiride
Placebo + Insulin (n=62) Glimepiride + Insulin (n=70)
Units/day
Weeks
0
25
50
75
100
0 4 8 12 16 20 24
†
*
*
* * * *
78 U/day
49 U/day
-38%
Mean insulin dosage required to
restore glycemic control
Weeks
18. • Glimipride is an effective tool in management of
type2 DM either as monotherapy or added to
other non SU drugs or insulin.
• Glimipride addresses more than one
pathophysiological target of type 2DM :
increase both 1st&2nd phase of insulin release.
Increase insulin sensitivity.
• Controls Glycemia with Less Insulin Secretion.
• Improve tt.adherence:
once daily,modest cost,less frequent side effects
and sustained action.
Sammary
20. Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update to a Position Statement of the AmericanDiabetes Association (ADA)
and the European Association for the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
21. Add ≥2 rapid insulin* injections
before meals ('basal-bolus’†
)
Change to
premixed insulin* twice daily
Add 1 rapid insulin* injections
before largest meal
• Start: Divide current basal dose into 2/3 AM,
1/3 PM or 1/2 AM, 1/2 PM.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 10U/day or 0.1-0.2 U/kg/day
• Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
• For hypo: Determine & address cause;
ê dose by 4 units or 10-20%.
Basal Insulin
(usually with metformin +/-
other non-insulin agent)
If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin.
(Consider initial
GLP-1-RA
trial.)
low
mod.
high
more flexible less flexible
Complexity
#
Injections
Flexibility
1
2
3+
If not
controlled,
consider basal-
bolus.
If not
controlled,
consider basal-
bolus.
• Start: 4U, 0.1 U/kg, or 10% basal dose. If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 4U, 0.1 U/kg, or 10% basal dose/meal.‡
If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
Figure 3.
Approach
to starting
& adjusting
insulin in
T2DM
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
22. • The risk for hypoglycemia in type 2 diabetes is
low, and newer insulin analogs have
demonstrated even lower rates of hypoglycemia
than older insulin products.
• Although weight gain can be expected with insulin
(similar to that seen with secretagogues), the
benefits of glycemic control clearly exceed the
small increases in body weight.
23
23. • Of note, insulin has been shown to reduce mortality
postmyocardial infarction,and more than 10 years
of follow-up in the United Kingdom Prospective
Diabetes Study (UKPDS) have clearly shown no
increase in cardiovascular risk.
• Finally, although multiple daily injections may be
required for patients with advanced, uncontrolled
diabetes, simpler insulin regimens are often highly
effective if initiated earlier in the course of diabetes
24
24. Basal Insulin Therapy
• Usual first step in beginning insulin therapy
• Continue oral agents and add basal insulin to optimize FPG
• A1C of up to 9.0% usually brought to goal (7%) by addition of
basal insulin therapy to oral agents
• Easy and generally safe: patient-directed treatment algorithms
with small risk of serious hypoglycemia
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes.
ADA/EASD Management of hyperglycemia in type 2 diabetes: A patient-centered approach. Diabetologia (2012) 55:1577–1596
25. Types of basal insulin
Intermediate-
Acting
(e.g. NPH, lente)
Long-Acting
(e.g. ultralente)
Long-Acting
Analogues
(glargine, detemir)
Onset 1-3 hr(s) 3-4 hrs 1.5-3 hrs
Peak 5-8 hrs 8-15 hrs
No peak with glargine,
dose-dependent peak
with detemir
Duration Up to 18 hrs 22-26 hrs
9-24 hrs (detemir);
20-24 hrs (glargine)
Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.
26. • Recombinant human insulin analogue1
• Basal (long-acting) insulin1
• Relatively constant peakless concentration/time profile over
24 hours1,2
• Once-daily SC administration1
• For adult and paediatric (aged 6 years) patients with type 1
diabetes2 and adults with type 2 diabetes
• Less nocturnal hypoglycaemia1
• More flexible dosing1
Insulin Glargine
27. Insulin Glargine Structure
1. Lantus® (insulin glargine) EMEA Summary of Product Characteristics. 2002.
2. McKeage K et al. Drugs. 2001;61:1599-1624.
Substitution
Extension
A chain
B chain
1
15105
10 15
20 Asn
30
Gly
Arg Arg
5 10 15 19 25
1
• Asparagine at position A21 replaced by glycine
– Provides stability
• Addition of 2 arginines at the C-terminus of the B chain
– Soluble at slightly acidic pH
28. Injection of an acidic solution
(pH 4.0)3
Microprecipitation of insulin glargine
in subcutaneous tissue (pH 7.4)3
Slow dissolution of free insulin glargine
hexamers from microprecipitates
(stabilised aggregates)3
Protracted action3
1. Lantus® (insulin glargine) EMEA Summary of Product Characteristics. 2002.
2. McKeage K et al. Drugs. 2001;61:1599-1624.
3. Kramer W. Exp Clin Endocrinol Diabetes. 1999;107(suppl 2):S52-S61.
Insulin Glargine
Mechanism of Action
The mechanics of sustained release1,2
29. PK/PD: Insulin Glargine has a flatter action profile
and a longer duration of action than NPH
Lepore M, et al. Diabetes 2000;49(12):2142–2148
Randomized four-way crossover euglycaemic clamp study comparing
the pharmacokinetics and pharmacodynamics of Insulin Glargine with
three commonly used basal insulin regimens (NPH, ultralente, CSII) in
patients with T1DM
30. Insulin glargine consistently achieves mean
HbA1C ≤ 7%
1. Riddle M, et al. Diabetes Care 2003;26:3080. 2. Gerstein HC, et al. Diabetes Med 2006;23:736. 3.
Bretzel RG, et al. Lancet 2008;371:1073. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364. 5.
Schreiber SA, et al. Diabetes Obes Metab 2007;9:31.
Baseline Study end
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
T-T-T1
(n = 367)
INSIGHT2
(n = 206)
APOLLO3
(n = 174)
INITIATE4
(n = 58)
Schreiber5
(n = 12,216)
HbA1C(%)
8.6 8.6 8.7 8.78.8
7.0 7.0 7.0 6.8 7.0
∆ -1.6 ∆ -1.6 ∆ -1.7 ∆ -2.0 ∆ -1.7
32. 33
Treat-to-Target: Insulin Glargine can be rapidly titrated
to achieve target glycaemic control
Starting daily dose
10 IU
Forced weekly titration using
predefined algorithm and
based on self-monitored FBG
Riddle MC, et al. Diabetes Care 2003;26(11):3080–3086
Mean daily dose at endpoint (IU/kg)
• NPH: 0.42
• Insulin Glargine: 0.48
• Randomized study in 756 insulin-naïve patients with T2DM who added
Insulin Glargine or NPH to their existing OAD therapy
33. •Basal insulin begun at a low dose (e.g., 0.1–0.2 units/kg per
day).
• A single injection of basal insulin administered before the
evening meal or at bedtime, at an initial dose of 0.1units/kg.
This will ensure that changes in blood glucose levels will be
gradual.
• Under special conditions, such as significant hyperglycemia
(HbA1c ≥9%) and/or obesity, a starting dose of 0.2 units/kg
may be used.
•An alternative, non-weight-based option is to start most
individuals empirically with 10 units, or in obesity up to 20
units, of basal insulin (i.e., long-acting or intermediate-acting).
How to Initiate Basal Insulin
34. Initiate& Titrate basal insulin
FPG, fasting plasma glucose
Nathan DM, et al. Diabetes Care 2009;32:193-203.
Initiate insulin with a single injection of a basal insulin
(Glargine)
Check
FPG
daily
In the event of hypoglycemia or
FPG level <3.89 mmol/L
(<70 mg/dL)
• Reduce bedtime insulin dose
by 4 units, or by 10% if >60
units
• Bedtime or morning long-acting insulin OR
• Bedtime intermediate-acting insulin
Daily dose: 10 units or 0.2 units/kg
INITIATE
• Increase dose by 2 units every 3
days until FPG (70–130 mg/dL)
• If FPG is >180 mg/dL, increase
dose by 4 units every 3 days
TITRATE
Continue regimen and
check HbA1c every 3 monthsMONITOR
35. 1.2.3 study: insulin glargine with addition of one, two or
three daily doses of glulisine
Subjects:
• Insulin naïve (785 entered study, 343 randomized) T2D (HbA1c ≥8.0%)
• Receiving 2 or 3 OHAs for ≥3 months (OHAs continued except sulfonylurea)
Randomization (subjects
with HbA1c >7.0%, n=434)
24 weeks
Insulin glargine
(n=785)
14 weeks
Additional insulin glulisine once daily (n=115)
Additional insulin glulisine twice daily (n=113)
Additional insulin glulisine three times daily (n=115)
Sanofi-aventis data on file (1.2.3 study)
Mean study entry values:
• HbA1c (%): 9.8
• BMI (kg/m2): 35.0
36. 1.2.3 study: intensification of Basal insulin
with mealtime glulisine injections improves glycemic
control
Sanofi-aventis data on file (1.2.3 study)
HbA1c in all subjects (n=785) = 9.8 at run in and 7.3 at randomization
Run in Randomization Wk 8 Wk 16 Wk 24
7.40
7.0
HbA1c(%)
10.19
10.19
10.16
7.44
7.29
8.0
9.0
10.0
Glulisine 1x
Glulisine 2x
Glulisine 3x
Responders in the whole
population (n=785)
Evolution of HbA1c in the
randomized population (n=343)
0
20
40
60
80
Subjects who
achieved
HbA1c <7.0%
with glargine
during run in
Additional
subjects who
achieved
HbA1c <7.0%
with glulisine
added to
glargine
All subjects
(n=785)
%achievingHbA1c<7.0
23%
37%
Glargine
(alone)
Glargine plus glulisine
(patients with HbA1c >7%)
37. 1.2.3 study: The Basal Plus strategy is associated with a
reduced level of hypoglycaemia
p=NS for all other pairwise comparisons
Sanofi-aventis data on file (1.2.3 study)
x1 x2 x3
0
1
2
3
4
5
Meanbodyweightchange
frombaseline(kg)
3.7 3.8 3.9
Glulisine
0
5
10
15
20
x1 x2 x3
Glulisine
Confirmedsymptomatichypo
(event/patient-year)
12.2
12.9
17.1
p=0.043
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
Severeorserioushypo
(event/patient-year)
x1 x2 x3
Glulisine
0.10
0.30
0.26
•At study end, the mean insulin dose (glargine + glulisine) was 84 +27, 80 + 50
and 81 + 66 U/day in the glulisine x1, x2 and x3 groups, respectively.
38. Summary
• Early and Tight management of type 2 DM is highly recommended to avoid
complications.
• Individualize treatment based upon patient needs, resources, and lifestyle
considerations
• CVS Safety issue must be considered in all patients.
• Structured patient Education &SMBG can minimize the hypoglycemia.
• Overcome the causes for patient resistance to insulin therapy with provider
belief and communication strategies
• Recognize when prandial insulin is required to avoid clinical inertia and the
concept of overbasalization
• Be willing to change strategies as needed to achieve goals i.e:
AVOID CLINICAL INNERTIA