Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults

Abstract

Introduction:Mechanisms for liraglutide-induced weight loss are poorly understood.Objective:We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals.Design:Participants (N=49, 18–75 years, body mass index: 30–40 kg m−2) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed.Results:Five-hour gastric emptying (AUC0–300 min) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80–1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5–0.6 mmol l−1 versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC0–300 min (by ∼26% versus placebo, P=0.02). Glucagon iAUC0–300 min decreased by ∼30%, and iAUC0–60 min for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk.Conclusion:Gastric emptying AUC0–300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity

“…GLP‐1 receptor agonists (RAs) have been shown to reduce body weight and blood glucose levels in people who are overweight or obese, with or without diabetes 6, 7, 8, 9, 10. Furthermore, activation of GLP‐1 receptors in the human brain helps to regulate appetite and food reward 11.…”

One‐year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26‐week extension to a 26‐week main trial

“…GLP‐1RAs reduce food intake and promote weight loss 1 and have the additional benefit of a low risk of hypoglycaemia compared with basal insulin 2, 3. These features may be helpful in overcoming some aspects of clinical inertia with respect to intensifying therapy in patients with T2D 4.…”

Biologic Responses to Weight Loss and Weight Regain: Report From an American Diabetes Association Research Symposium

“…However, clinical development of pramlintide as a standalone weight-loss medication was discontinued in favor of combination approaches. Liraglutide, a GLP-1 receptor agonist that has been available as a diabetes medication since 2010, also has effects on satiety and food intake (95). Liraglutide was recently approved for the treatment of obesity.…”