Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial

Diabetes Obes Metab. 2024 Mar;26(3):911-923. doi: 10.1111/dom.15386. Epub 2023 Nov 28.

Abstract

Aim: To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals.

Methods: A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software.

Results: Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary.

Conclusion: In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.

Keywords: meta-analysis; obesity; semaglutide; systematic review; weight loss; without diabetes.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use
  • Female
  • Glucagon-Like Peptides* / administration & dosage
  • Glucagon-Like Peptides* / adverse effects
  • Glucagon-Like Peptides* / therapeutic use
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Obesity* / complications
  • Obesity* / drug therapy
  • Overweight* / complications
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Weight Loss* / drug effects

Substances

  • semaglutide
  • Glucagon-Like Peptides
  • Anti-Obesity Agents
  • Hypoglycemic Agents