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 (AUC 0–300 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 C max and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC 0–300 min (by∼ 26% versus placebo, P= 0.02). Glucagon iAUC 0–300 min decreased by∼ 30%, and iAUC 0–60 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 AUC 0–300 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.