Effects of Exenatide and Lifestyle Modification on Body Weight and Glucose Tolerance in Obese Subjects With and Without Pre-Diabetes

Abstract

OBJECTIVETo assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance (IGT) or impaired fasting glucose (IFG).RESEARCH DESIGN AND METHODSObese subjects (n = 152; age 46 ± 12 years, female 82%, weight 108.6 ± 23.0 kg, BMI 39.6 ± 7.0 kg/m2, IGT or IFG 25%) were randomized to receive exenatide (n = 73) or placebo (n = 79), along with lifestyle intervention, for 24 weeks.RESULTSExenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo (exenatide − placebo, P < 0.001). Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5% (P < 0.001). Both groups reduced their daily calorie intake (exenatide, −449 cal; placebo, −387 cal). IGT or IFG normalized at end point in 77 and 56% of exenatide and placebo subjects, respectively.CONCLUSIONSExenatide plus lifestyle modification decreased caloric intake and resulted in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG.

Glucagon-like peptide-1 receptor agonist treatment reduces beta cell mass in normoglycaemic mice

“…While GLP-1RA treatment increases beta cell mass in animal models of diabetes, we now show a reduction in beta cell mass in normoglycaemic mice. GLP1-RA treatment of non-diabetic obese individuals results in weight loss and improved beta cell function [12,13]. Therefore, it is relevant to understand how beta cell mass adapts during GLP1-RA treatment under normoglycaemic conditions and different dietary situations.…”

“…GLP-1RAs decrease body weight and are associated with reduced blood pressure, improved lipid profiles and improved endothelial function in patients with type 2 diabetes [10,11]. Therefore, these compounds have also been evaluated in non-diabetic individuals with obesity or cardiovascular disease [12][13][14][15]. However, the effect of GLP-1RAs on beta cells in these normoglycaemic conditions is not clear.…”

Mosapride citrate, a 5-HT₄ receptor agonist, increased the plasma active and total glucagon-like peptide-1 levels in non-diabetic men

“…Given the fact that diabetes develops when the insulin secretion by beta cells is insufficient to compensate for insulin resistance [22,23] and GLP-1 reportedly inhibits apoptosis in humans, the increase in the GLP-1 concentration may be important for improving beta cell function [24]. In addition, the increase in GLP-1 may protect against obesity because of the anti-obesity effect GLP-1 [25][26][27][28].…”

Impact of Newer Medications for Type 2 Diabetes on Body Weight

“…One study showed −5.1 kg of weight loss on exenatide vs −1.6 kg on placebo after 26 weeks of treatment in addition to lifestyle intervention, with significantly greater normalization of prediabetes in the exenatide group (77 % and 56 %, respectively) [55]. Another study of 41 obese women, conducted in a double blind, placebo controlled crossover fashion demonstrated that 16 weeks of exenatide 10 mcg bid without any lifestyle intervention resulted in an average of −2.5 kg weight loss compared with −0.4 kg on placebo, as well as a significant decrease in waist circumference [56].…”