TREATMENT OF T2DM PRESENT AND FUTURE

Dr.PARAMESH.S BSc,M.D,D.DiabMEDICAL DIRECTOR BANGALORE DIABETES CENTREMEDISYS CLINISEARCH INDIA PVT LTD :Dr.PARAMESH.S BSc,M.D,D.DiabMEDICAL DIRECTOR BANGALORE DIABETES CENTREMEDISYS CLINISEARCH INDIA PVT LTD


Major Classes of Medications :Major Classes of Medications 1. Drugs that sensitize the body to insulin and/or control hepatic glucose production 2. Drugs that stimulate the pancreas to make more insulin 3. Drugs that slow the absorption of starches Thiazolidinediones Biguanides Sulfonylureas Meglitinides Alpha-glucosidase inhibitors


Biguanides :Biguanides Biguanides decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake. Efficacy Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9 mmol/L) Reduce A1C 1.0-2.0% Other Effects Diarrhea and abdominal discomfort Lactic acidosis if improperly prescribed Cause small decrease in LDL cholesterol level and triglycerides No specific effect on blood pressure No weight gain, with possible modest weight loss Contraindicated in patients with impaired renal function (Serum Cr > 1.4 mg/dL for women, or 1.5 mg/dL for men) Medications in this Class: metformin (Glucophage), metformin hydrochloride extended release (Glucophage XR)


Sulfonylureas :Sulfonylureas Sulfonylureas increase endogenous insulin secretion Efficacy Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9 mmol/L) Reduce A1C by 1.0-2.0% Other Effects Hypoglycemia Weight gain No specific effect on plasma lipids or blood pressure Generally the least expensive class of medication Medications in this Class: First generation sulfonylureas: chlorpropamide (Diabinese), tolazamide, acetohexamide (Dymelor), tolbutamide Second generation sulfonylureas: glyburide (Micronase, Glynase, and DiaBeta), glimepiride (Amaryl), glipizide (Glucotrol, Glucotrol XL) gliclazide (dianorm)


Meglitinides :Meglitinides Meglitinides stimulate insulin secretion (rapidly and for a short duration) in the presence of glucose. Efficacy Decreases peak postprandial glucose Decreases plasma glucose 60-70 mg/dl (3.3-3.9 mmol/L) Reduce A1C 1.0-2.0% Other Effects Hypoglycemia (although may be less than with sulfonylureas if patient has a variable eating schedule) Weight gain No significant effect on plasma lipid levels Safe at higher levels of serum Cr than sulfonylureas Medications in this Class: repaglinide (Prandin), nateglinide (Starlix)


Alpha-glucosidase Inhibitors :Alpha-glucosidase Inhibitors Alpha-glucosidase inhibitors block the enzymes that digest starches in the small intestine Efficacy Decrease peak postprandial glucose 40-50 mg/dl (2.2-2.8 mmol/L) Decrease fasting plasma glucose 20-30 mg/dl (1.4-1.7 mmol/L) Decrease A1C 0.5-1.0% Other Effects Flatulence or abdominal discomfort No specific effect on lipids or blood pressure No weight gain Contraindicated in patients with inflammatory bowel disease or cirrhosis Medications in this Class: acarbose (Precose), miglitol (Glyset) voglibose


Thiazolidinediones :Thiazolidinediones Thiazolidinediones decrease insulin resistance by making muscle and adipose cells more sensitive to insulin. They also suppress hepatic glucose production. Efficacy Decrease fasting plasma glucose ~35-40 mg/dl (1.9-2.2 mmol/L) Reduce A1C ~0.5-1.0% 6 weeks for maximum effect Other Effects Weight gain, edema Hypoglycemia (if taken with insulin or agents that stimulate insulin release) Contraindicated in patients with abnormal liver function or CHF Improves HDL cholesterol and plasma triglycerides; usually LDL neutral Medications in this Class: pioglitazone (Actos), rosiglitazone (Avandia), [troglitazone (Rezulin) - taken off market due to liver toxicity]


Efficacy of Monotherapy with Oral Diabetes Agents :Efficacy of Monotherapy with Oral Diabetes Agents DeFronzo Annals of Internal Medicine 1999;131:281-303 Nathan N Engl J Med 2002; 347:1342-1349


Management of HyperglycemiaStarting Basal Insulin :Management of HyperglycemiaStarting Basal Insulin Consider when A1C >7% on oral combination therapy Continue oral agent(s) at same dosage Add single, evening insulin dose (10 U) NPH (bedtime) Premix (evening meal) Glargine (bedtime or with evening meal) Titrate dose weekly according to fasting SMBG (FPG) Increase 4 U if FPG >140 mg/dL Increase 2 U if FPG = 120 to 140 mg/dL Treat to target (usually <120 mg/dL) Reduce morning oral agent dosage if daytime hypoglycemiaoccurs


Management of HyperglycemiaAdvancing to Two Injections :Management of HyperglycemiaAdvancing to Two Injections Consider when FPG acceptable but A1C >7% on one injection Insulin options To bedtime NPH, add morning NPH To suppertime premix, add morning premix To glargine, add regular, aspart, glulisine, or lispro to main meal Oral agent options Usually stop sulfonylureas Continue metformin for weight control? Continue glitazones for glycemic stability?


Management of HyperglycemiaAdvancing to Basal-Bolus Regimen :Management of HyperglycemiaAdvancing to Basal-Bolus Regimen Consider when A1C >7% on two injections Insulin options Bedtime and morning NPH + regular, aspart, glulisine, or lispro with each meal Glargine + regular, aspart, glulisine, or lispro with each meal Oral agent options Usually stop sulfonylureas Continue metformin for weight control? Continue glitazones for glycemic stability?


Treatment of Type 2 Diabetes :Treatment of Type 2 Diabetes Diagnosis


Slide 15 :Combination Therapy for Type 2 Diabetes Biguanides Sulfonylureas


Slide 16 :Combination Therapy for T 2 DM Fixed Combination Pills Sulfonylurea + Biguanide Glyburide + Metformin - Glucovance Glipizide + Metformin - Metaglip Thiazolidinedione + Biguanide Rosiglitazone + Metformin - Avandamet


Slide 30 :AVE DUTOGLIPTIN ALOGLIPTIN B110356


SGLT INHIBITORS :SGLT INHIBITORS


SGLT INHIBITORS :Sergliflozin (GW869682X) - GSK AVE 2268 -AVENTIS Dapagliflozin (BMS 512148) SGLT INHIBITORS SGLT2 inhibitors have significant potential in the treatment of type 2 diabetes as a class of drugs that can effectively lower blood glucose while avoiding weight gain, hypoglycemia, and edema