Background: The Centers for Disease Control and Prevention (CDC) reports that 42% of adults in the United States (US) are obese, and 10% are severely obese. Obesity has many known associated health risks, and successful treatment has been shown to decrease those risks. While management always includes diet and lifestyle changes, drug therapy can improve weight loss. Drug therapy choices for long-term use include a combination phentermine-topiramate, combination bupropion-naltrexone, orlistat, and glucagon-like peptide-1 receptor agonists (GLP- 1RAs).
Objectives: This review will summarize evidence comparing the safety and efficacy of GLP- 1RAs with other pharmacologic treatments to achieve and maintain weight loss, improve quality of life, and reduce morbidity in obese adults.
Methods: PubMed, Embase, Google Scholar, and Cochrane databases were searched to identify studies of overweight or obese adults, with or without type 2 diabetes (T2DM), treated for obesity with a GLP-1RA and/or other regimens and reporting findings as mean percentage body weight loss. We preferentially chose meta-analyses and primary studies in patients without T2DM. We excluded studies published before 2018 or in a language other than English.
Results: Over 52 weeks, liraglutide reduced mean body weight percentage by 4.81% (95% CI: 4.23%-5.39%). Between a 12-68 week period in patients receiving semaglutide, three meta- analyses reported reduced weight by 12.57% [97% CI 10.35%-14.80%,) 10.55% (95% CI 6.96%-14.13%,) and 10.09% (95% CI: 8.33%-11.84%.) Tirzepatide, a novel GLP-1RA and GIP agonist currently in phase-3 clinical control trials, showed that over 72 weeks, the mean weight percentage decrease for 5mg was 15.0% (95% CI 14.2-15.9), 10mg was 19.5% (95% CI 18.5- 20.4), and 15mg was 20.9% (95% CI 19.9-21.8.) Each of the GLP-1RA agents (including tirzepatide) has been found to improve cardiometabolic risk factors. Phentermine-topiramate reduced mean body weight percentage by 8.45% (95% CI, 7.89%–9.01%) after 52-56 weeks. Bupropion-naltrexone reduced mean body weight percentage by 3.01% (95% CI, 2.47%–3.54%) over 56 weeks. Finally, orlistat reduced mean body weight percentage by 2.78% (95% CI, 2.36%–3.20%) after 1-4 years. Tirzepatide, although not approved for obesity, showed the most significant weight loss.
Conclusion: Pharmacotherapy with diet and exercise is more effective than diet and exercise alone in achieving weight loss. The GLP-1RAs are effective for weight loss, with semaglutide more effective than other approved agents. When choosing pharmacotherapy, utilizing GLP-1RA and/or dual GLP-1RA/GIP agonists can improve cardiometabolic risk factors and quality of life and are more effective than any other approved agent.
Overholser A. Comparison of GLP-1RAs vs Other Pharmacotherapy for Obesity: A Clinical Review. University of Lynchburg DMSc Doctoral Project Assignment Repository. 2023; 5(2).
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