Endocrine Abstracts

In 1996, we showed that GLP-1 is a satiety hormone in humans, and increased post-prandial GLP-1 levels following high protein meals have shown to be at least partially responsible for the high satiating effect of protein. The natural ligands to stimulate GLP-1 release seem to be peptide fragments and monoacylglycerides.

The once-daily GLP-1 analogue liraglutide at doses up to 3.0 mg was compared with placebo or orlistat over 104 weeks as adjunct to diet and exercise in 564 obese individuals with without diabetes. After 52 weeks, mean weight loss was greater with liraglutide 3.0 mg (7.8 kg) vs placebo (2.0 kg) or orlistat (3.9 kg) [both P≤0.0001].

In the SCALE Obesity and Prediabetes 160-week double-blind trial, 2254 individuals with prediabetes and obesity or overweight with comorbidities, were randomized 2:1 to liraglutide 3.0 mg (n=1505) or placebo (n=749). The primary objective was to evaluate the proportion of patients with type 2 diabetes at 160 weeks. Time to onset of diabetes was 2.7 times longer with liraglutide 3.0 mg (n=1505) vs placebo (n=749) [95% CI: 1.9–3.9, P<0.0001] (HR: 0.2). At week 160, mean weight loss from baseline was 6.1% with liraglutide 3.0 mg vs. 1.9% with placebo (P<0.0001).

Liraglutide 3.0 mg was well-tolerated, with mild or moderate gastrointestinal side effects being the most frequently reported. Serious adverse events occurred in 15.1% of individuals in the liraglutide group vs, 12.9% with placebo. Gallbladder-related events (2.9 vs 1.2/100 patient years of observation (PYO)) and confirmed pancreatitis (0.29 vs 0.13 events/100 PYO) were low, but more frequent with liraglutide 3.0 mg vs placebo.

In summary, GLP-1 is an endogenous satiety hormone involved in appetite regulation and GLP-1 receptor agonists can reduce body weight and diabetes risk over 3 years.