Abstract
Because the causes of obesity involve genetic, epigenetic, biological, environmental, sociocultural, dietary, and behavioural factors and their interactions, 1 Gadde KM Martin CK Berthoud HR Heymsfield SB Obesity: pathophysiology and management. J Am Coll Cardiol. 2018; 71: 69-84 Crossref PubMed Scopus (205) Google Scholar weight management interventions manifest considerable treatment response heterogeneity. For decades, anti-obesity drug development primarily targeted central neurotransmitters regulating appetite and food intake. Although orlistat, a gastric and pancreatic lipase inhibitor approved in 1999, was an exception, its weight loss efficacy is marginal. 1 Gadde KM Martin CK Berthoud HR Heymsfield SB Obesity: pathophysiology and management. J Am Coll Cardiol. 2018; 71: 69-84 Crossref PubMed Scopus (205) Google Scholar Liraglutide, a GLP-1 receptor agonist, at a dose of 3·0 mg injected daily was associated with a placebo-subtracted weight loss of 4·0% to 5·4% over 1 year. 1 Gadde KM Martin CK Berthoud HR Heymsfield SB Obesity: pathophysiology and management. J Am Coll Cardiol. 2018; 71: 69-84 Crossref PubMed Scopus (205) Google Scholar Semaglutide 2·4 mg, another GLP-1 receptor agonist injected weekly, yielded a placebo-subtracted weight loss of 6·2% to 12·4% after 68 weeks in phase 3 trials 2 Davies M Færch L Jeppesen OK et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397: 971-984 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar , 3 Wadden TA Bailey TS Billings LK et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021; 325: 1403-1413 Crossref PubMed Scopus (126) Google Scholar , 4 Wilding JPH Batterham RL Calanna S et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384: 989 Crossref PubMed Scopus (374) Google Scholar and was approved in June, 2021, for obesity treatment. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trialTreatment with cagrilintide in people with overweight and obesity led to significant reductions in bodyweight and was well tolerated. The findings support the development of molecules with novel mechanisms of action for weight management. Full-Text PDF
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