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Endocrinology AdvisorSemaglutide and Phentermine/Topiramate Linked to Greatest Body Weight Reduction

Semglutide with phentermine/topiramate resulted in better weight loss and waist circumference decrease in obese patients than other weight loss medicines.

A comprehensive systematic review of studies has revealed that semaglutide and phentermine/topiramate are associated with the greatest reduction in body weight and waist circumference among patients with obesity. The research, published in Diabetes, Obesity and Metabolism, compared these drugs against other approved medications for obesity management, providing key insights into their efficacy and safety.

Key Points:

  • The review included 168 trials with 97,938 patients, median age 46.9 years, 25.5% men, and median BMI of 35.8 kg/m².
  • Semaglutide and phentermine/topiramate showed the highest weight loss effects at 12 months (MD, -9.02 kg and 8.10 kg respectively).
  • These two drugs also resulted in the greatest reductions in waist circumference (MD, -7.84 cm and -6.20 cm respectively).
  • Naltrexone/bupropion was associated with a lower risk of cardiovascular death compared to placebo (OR, 0.62; 95% CI, 0.39-0.99), but no significant differences were found between all drugs for other cardiovascular outcomes.

Additional Points:

  • All drugs were associated with increased weight loss compared to placebo at 12 months.
  • The risk of withdrawal was increased with all drugs compared to placebo, with naltrexone/bupropion having the highest odds.
  • Semaglutide, liraglutide, and orlistat showed the greatest reductions in HbA1c levels compared to placebo.
  • Study limitations include a high risk of bias in several trials and insufficient prevalence of the primary outcome of cardiovascular death.


  • Semaglutide and phentermine/topiramate were found to be most effective in reducing body weight and waist circumference at 12 months, with lower or no significant difference in risks of withdrawal compared to other drugs.

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Did You Know?
Pediatric obesity has become a significant global health concern, with the prevalence of obesity among children and adolescents aged 5-19 years having risen from just 4% in 1975 to over 18% in 2016, according to the World Health Organization.

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