Dataset Information

Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.

ABSTRACT:

Objective

This study tested the hypothesis that treatment with the glucagon-like peptide-1/glucagon receptor agonist SAR425899 would lead to a smaller decrease in sleeping metabolic rate (SMR; kilocalories/day) than expected from the loss of lean and fat mass (metabolic adaptation).

Methods

This Phase 1b, double-blind, randomized, placebo-controlled study was conducted at two centers in inpatient metabolic wards. Thirty-five healthy males and females with overweight and obesity (age = 36.5 ± 7.1 years) were randomized to a calorie-reduced diet (-1000 kcal/d) and escalating doses (0.06-0.2 mg/d) of SAR425899 (n = 17) or placebo (n = 18) for 19 days. SMR was measured by whole-room calorimetry.

Results

Both groups lost weight (-3.68 ± 1.37 kg placebo; -4.83 ± 1.44 kg SAR425899). Those treated with SAR425899 lost more weight, fat mass, and fat free mass (p < 0.05) owing to a greater achieved energy deficit than planned. The SAR425899 group had a smaller reduction in body composition-adjusted SMR (p = 0.002) as compared with placebo, but not 24-hour energy expenditure. Fat oxidation and ketogenesis increased in both groups, with significantly greater increases with SAR425899 (p < 0.05).

Conclusions

SAR425899 led to reduced selective metabolic adaptation and increased lipid oxidation, which are believed to be beneficial for weight loss and weight-loss maintenance.

SUBMITTER: Corbin KD

PROVIDER: S-EPMC9881753 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.

Corbin Karen D KD Carnero Elvis A EA Allerton Timothy D TD Tillner Joachim J Bock Christopher P CP Luyet Pierre-Philippe PP Göbel Britta B Hall Kevin D KD Parsons Stephanie A SA Ravussin Eric E Smith Steven R SR

Obesity (Silver Spring, Md.) 20230201 2

<h4>Objective</h4>This study tested the hypothesis that treatment with the glucagon-like peptide-1/glucagon receptor agonist SAR425899 would lead to a smaller decrease in sleeping metabolic rate (SMR; kilocalories/day) than expected from the loss of lean and fat mass (metabolic adaptation).<h4>Methods</h4>This Phase 1b, double-blind, randomized, placebo-controlled study was conducted at two centers in inpatient metabolic wards. Thirty-five healthy males and females with overweight and obesity (a ...[more]

PMID: 36695055

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Dataset Information

Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.

Objective

Methods

Results

Conclusions

Publications

Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.

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