Glucagon‐like peptide‐1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial. Issue 2 (25th January 2023)

• Record Type: Journal Article
• Authors: Corbin, Karen D.; Carnero, Elvis A.; Allerton, Timothy D.; Tillner, Joachim; Bock, Christopher P.; Luyet, Pierre‐Philippe; Göbel, Britta; Hall, Kevin D.; Parsons, Stephanie A.; Ravussin, Eric; Smith, Steven R.
• Is Part Of: Obesity. Volume 31:Issue 2(2023)
• Page Start: 350
• Page End: 362
• Publication Date: 2023-01-25
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.23633
• Languages: English
• ISSNs: 1930-7381

Abstract

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.