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

Sep 4, 2013International journal of obesity (2005)

Daily liraglutide’s effects on stomach emptying, blood sugar, appetite, and energy use in obese adults without diabetes

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Abstract

Liraglutide 3.0 mg led to a 23% reduction in 1-hour gastric emptying compared to placebo.

Both liraglutide doses (1.8 mg and 3.0 mg) reduced fasting glucose levels by 0.5-0.6 mmol/L compared to placebo.
Liraglutide 3.0 mg significantly decreased insulin and C-peptide levels by approximately 20% compared to placebo.
Mean postprandial satiety and fullness ratings increased with liraglutide treatment, while hunger and prospective food consumption decreased.
Ad libitum energy intake was reduced by approximately 16% with both liraglutide doses.
Liraglutide treatment was associated with a relative increase in fat oxidation and a decrease in carbohydrate oxidation.

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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 ((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 Cmax 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.

Key numbers

23%

Decrease in 1-hour gastric emptying

Liraglutide 3.0 mg vs. placebo

0.5–0.6 mmol/l

Reduction in fasting glucose

Both liraglutide doses vs. placebo

16%

Reduction in energy intake

Both liraglutide doses vs. placebo

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

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