Maintenance of diet with exenatide lasts-the model study

Results: Weight loss improves glycemic control and cardiovascular risk factors in patients with type 2 diabetes. Patients are often able to lose weight through caloric restriction but have difficulty in maintaining weight loss. The purpose of this study was to test the hypothesis that exenatide 10ug BID, a GLP-1 analog, would prevent weight regain after a very low calorie diet (VLCD) in patients with T2DM. 226 patients with early stage T2DM, either on metformin alone or 'diet controlled', were enrolled into a two-phase protocol. The first phase was a macronutrient balanced liquid VLCD (890 kcal/d as 5 Health One™ shakes) targeted to achieve a weight loss of at least -7.5% initial body weight. The second step was a one-week transition to a weight maintenance diet followed by randomization to exenatide 10ug BID or placebo for 12 months. Herein we report the effects on weight and HbA1C out to month 6 as a pre-specified interim analysis. At baseline, volunteers had an HBA1C of 6.8 + 1.3% and weighed 102.9 + 17.5kg. 121 patients (54%) completed the VLCD portion of the study and were randomized. Weight loss for those who completed the VLCD averaged -8.8 + 2.2% of initial body weight with an absolute drop in HbA1C of -0.67 + 0.67%. Exenatide was well tolerated and there were no serious adverse events attributed to the treatment. Six months after randomization weight regain was 1.8 + 3.6 kg in the placebo treated patients vs. 0.3 + 4.7 in the exenatide treated patients (ANOVA p < 0.05 for comparison of change at M6). Over time HbA1C (%) increased in the placebo treated patients (randomization to M6, + 0.16 + 0.4; p < 0.05) but remained low in the exenatide treated patients (change from baseline -0.09 + 0.5; p = 0.0015 for time by treatment interaction; ANOVA). This stepped approach (VLCD followed by exenatide), enabling substantial and sustained weight loss (∼9%) coupled by exceptional levels of glycemic control (A1C ∼6%), offers an alternate therapeutic approach to managing early Type 2 diabetes where targeting weight gain and preventing re-gain is a means to exercise optimal metabolic control.