As part of a study whose findings were recently published in the journal Obesity, the researchers sought to test the hypothesis that treatment with a 1-GLP (glucagon-like peptide-1) agonist/glucagon receptor agonist SAR425899 will lead to a smaller decrease in sleeping metabolic rate (SMR) , kcal/day) than expected as a result of fat mass loss (metabolic adaptation).
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This is a phase 1b study which was conducted in a double-blind, controlled in vivo format. As part of it, 35 patients were recruited from two hospitalization centers for the treatment of metabolic diseases. The subjects were healthy overweight/obese men and women (aged 36.5 ± 7.1 years). The subjects were randomly divided into one of 2 groups: a group that was treated with SAR42589 in increasing doses (0.06-0.2 mg/day) and in combination with a reduced calorie diet (1000-kcal/day) or an invo group (n=17 and n =18, respectively), and this for 19 days. SMR is measured using whole-room calorimetry.
The results of the study demonstrated that weight loss was recorded in both study groups (−3.68 ± 1.37 kg in the placebo group and −4.83 ± 1.44 kg in the intervention group). Those treated with SAR425899 lost more weight, fat mass and fat-free mass (p < 0.05), and this was due to the energy deficit which was greater than expected. Compared to the in vivo group, the SAR425899 group had a smaller decrease in SMR adjusted for body composition (p=0.002). On the other hand, there was no decrease in energy expenditure for 24 hours among the first ones. Fatty acid oxidation and ketogenesis were increased in both groups, a trend that was even more significant in the SAR425899 groupJ(p < 0.05).
The results of the study demonstrated that SAR425899 leads to a reduction in selective metabolic adaptation and an increase in lipid oxidation. Both of these processes are considered effective for weight loss and weight loss maintenance.
source:
Corbin KD, Carnero EA, Allerton TD, Tillner J, Bock CP, Luyet PP, Göbel B, Hall KD, Parsons SA, Ravussin E, Smith SR. Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial. Obesity (Silver Spring). 2023 Feb;31(2):350-362. doi: 10.1002/oby.23633. PMID: 36695055; PMCID: PMC9881753.