Diabetes Update Part 2 of 3 Division of

Diabetes Update Part 2 of 3 Division of Endocrinology Department of Medicine Wayne State University Medical School Detroit, Michigan 1

Why the Interest in Incretins ? 2

The Incretin Defect in Type 2 Diabetes Incretin “Defect” Insulin Resistance Relative Insulin Deficiency Hyperglycemia Type 2 Diabetes Incretin effect accounts for up to 70% of the insulin response to oral glucose intake 1 1. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004; 287(2): E 199 -E 206. 4

ADA/EASD Consensus Statement Includes a GLP-1 Receptor Agonist STEP 1 At diagnosis: Lifestyle + MET If A 1 C ≥ 7% STEP 2 Tier 1: Well-validated core therapies* Lifestyle + MET + SFU Lifestyle + MET + basal insulin MET, metformin PIO, pioglitazone SFU, sulfonylurea STEP 3 OR Tier 2: Less well-validated therapies* Lifestyle + MET + GLP-1 receptor agonist† Lifestyle + MET + PIO “If hypoglycemia is particularly Lifestyle + MET + undesirable…” and/or “promotion PIO + SFU of weight loss is a consideration…” Lifestyle + MET + basal insulin Lifestyle + MET + intensive insulin *Validation based on clinical trials and clinical judgment. †Insufficient clinical use to be confident regarding safety. Adapted from Nathan DM, et al. Diabetes Care. 2009. 7

Liraglutide (Victoza) and Exenatide (Byetta) Newer GLP 1 analogue. Indicated in monotherapy or in combination with metformin, SU, TZD, or combination therapy. Dosed once or twice daily Uses the convenient pen. Maintains weight loss and glycemic control. EXUBERA® (insulin human [r. DNA origin]) Inhalation Powder

Why Insulin in Type 2 Diabetes? 9

Mimicking Physiology: Basal and Prandial Insulin Lunch Dinner Plasma Insulin Breakfast Prandial Insulin 3/day Plus 4: 00 8: 00 12: 00 16: 00 Time 20: 00 24: 00 Basal 1/day 4: 00 8: 00 12