PMID- 34877513 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220429 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 42 DP - 2021 Dec TI - Association of Glucagon-like Peptide 1 Analogs and Agonists Administered for Obesity with Weight Loss and Adverse Events: A Systematic Review and Network Meta-analysis. PG - 101213 LID - 10.1016/j.eclinm.2021.101213 [doi] LID - 101213 AB - BACKGROUND: Comparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown. METHODS: We performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of >/=12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE). FINDINGS: 64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m(2); trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide >/=1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide 1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I(2) >50%) in WL and AEs reflected magnitude, not direction of effect. CI - (c) 2021 The Author(s). FAU - Vosoughi, Kia AU - Vosoughi K AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. FAU - Atieh, Jessica AU - Atieh J AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. FAU - Khanna, Lehar AU - Khanna L AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. FAU - Khoshbin, Katayoun AU - Khoshbin K AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. FAU - Prokop, Larry J AU - Prokop LJ AD - Library-Public Service Department, Mayo Clinic, Rochester, MN. FAU - Davitkov, Perica AU - Davitkov P AD - Veterans Affairs Northeast Ohio Healthcare System and Case Western Reserve University, Cleveland, OH. FAU - Murad, M Hassan AU - Murad MH AD - Division of Preventive Medicine, Department of Medicine, Mayo Clinic, Rochester, MN. FAU - Camilleri, Michael AU - Camilleri M AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. LA - eng PT - Journal Article DEP - 20211127 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC8633575 COIS- Dr. Camilleri is supported by grant R01-DK67071 from National Institutes of Health for mechanistic studies of obesity including GLP-1 agonists/analogs. Dr. Camilleri serves on an advisory board for Phenomix Sciences regarding the company's development of a test to predict weight loss response to obesity therapy, and he is a stockholder in the company. Phenomix Sciences has obtained an exclusive license to Dr. Camilleri's and a Mayo Clinic co-investigator's biomarker technology, submitted patent, and know-how to develop a biomarker to predict response to obesity pharmacotherapy. Dr. Camilleri also serves as a consultant to Kallyope for the company's development program regarding obesity (the consulting fee is paid to his employer, Mayo Clinic). Dr. Camilleri has a patent application pending regarding obesity metabolomics to identify different phenotypes with the United States Patent and Trademark Office. The other authors have no conflicts of interest. EDAT- 2021/12/09 06:00 MHDA- 2021/12/09 06:01 PMCR- 2021/11/27 CRDT- 2021/12/08 06:35 PHST- 2021/08/31 00:00 [received] PHST- 2021/10/29 00:00 [revised] PHST- 2021/11/09 00:00 [accepted] PHST- 2021/12/08 06:35 [entrez] PHST- 2021/12/09 06:00 [pubmed] PHST- 2021/12/09 06:01 [medline] PHST- 2021/11/27 00:00 [pmc-release] AID - S2589-5370(21)00494-6 [pii] AID - 101213 [pii] AID - 10.1016/j.eclinm.2021.101213 [doi] PST - epublish SO - EClinicalMedicine. 2021 Nov 27;42:101213. doi: 10.1016/j.eclinm.2021.101213. eCollection 2021 Dec.