{"doi":"10.1002/oby.23633","title":"<scp>Glucagon‐like peptide</scp>‐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.","journal":"Obesity","year":2023,"id":331606,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":300732,"name":"Elvis Á. Carnero","orcid":"0000-0003-0442-4217","position":1,"is_corresponding":false},{"id":514652,"name":"Timothy D. Allerton","orcid":"0000-0001-6364-5787","position":2,"is_corresponding":false},{"id":711421,"name":"J. Tillner","orcid":"0000-0002-2798-2732","position":3,"is_corresponding":false},{"id":300731,"name":"C. Bock","orcid":"0000-0001-5229-5347","position":4,"is_corresponding":false},{"id":1057630,"name":"Pierre‐Philippe Luyet","orcid":null,"position":5,"is_corresponding":false},{"id":1057631,"name":"Britta Göbel","orcid":null,"position":6,"is_corresponding":false},{"id":251344,"name":"Kevin D. Hall","orcid":"0000-0003-4062-3133","position":7,"is_corresponding":false},{"id":1057632,"name":"Stephanie A. Parsons","orcid":null,"position":8,"is_corresponding":false},{"id":235348,"name":"Éric Ravussin","orcid":"0000-0003-2129-547X","position":9,"is_corresponding":false},{"id":300728,"name":"Steven R. Smith","orcid":"0000-0002-5098-8147","position":10,"is_corresponding":false},{"id":342464,"name":"Karen D. Corbin","orcid":"0000-0003-2065-0003","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:09:25.015646Z","pmid":"36695055","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}