Semaglutide for Weight Loss in Non-Diabetic Obesity: A Meta-Analytic Overview of Efficacy and Safety

Introduction: Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes — A Systematic Review and Meta-Analysis

Obesity continues to rise globally, necessitating evidence-based, long-term treatment strategies that are both effective and safe. For individuals with obesity who do not have type 2 diabetes, semaglutide has emerged as a promising intervention. The systematic review and meta-analysis titled “Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes“ by Tan et al., published in the Journal of the ASEAN Federation of Endocrine Societies in 2022, aims to clarify semaglutide’s therapeutic value in this specific population.

This analysis consolidates findings from multiple randomized controlled trials to assess semaglutide’s impact on weight reduction and to evaluate the associated risk of adverse events.

Study Scope and Methodology

The meta-analysis reviewed 4 randomized controlled trials encompassing 3,613 participants with obesity but without type 2 diabetes. These studies compared a treatment group receiving subcutaneous semaglutide with a placebo group.

Key inclusion criteria:

• Adults with obesity (BMI ≥30) 
• No diagnosis of type 2 diabetes 
• Treatment duration and dosing schedules consistent with semaglutide’s weight-management protocol 

The primary outcome was percentage change in body weight, while secondary outcomes included adverse events, treatment discontinuation, and serious complications.

Results: Significant Weight Loss in the Semaglutide Group

Semaglutide demonstrated robust weight-loss benefits:

• The mean weight reduction was -11.85% compared to placebo (95% CI: -12.81% to -10.90%, p < 0.00001). 
• These findings reinforce semaglutide’s consistent performance in reducing body weight among non-diabetic individuals with obesity. 

This result aligns with other high-profile trials such as STEP 1 and STEP 5, further validating semaglutide’s efficacy across various demographic groups.

Safety and Adverse Events

While effective, semaglutide was also associated with an increased risk of side effects:

• Gastrointestinal adverse events were 1.59 times more likely in the semaglutide group (RR 1.59; 95% CI: 1.34–1.88; p < 0.00001). 
• The risk of treatment discontinuation due to side effects was 2.19 times higher (RR 2.19; 95% CI: 1.36–3.55; p = 0.001). 
• The risk of serious adverse events was 1.6 times higher (RR 1.60; 95% CI: 1.24–2.07; p = 0.0003). 

Most serious adverse events were related to gastrointestinal and hepatobiliary issues, such as:

• Acute pancreatitis 
• Cholelithiasis (gallstones) 

These findings underscore the importance of monitoring and managing side effects, especially during dose escalation.

Clinical Implications: Balancing Benefit and Risk

This systematic review affirms semaglutide’s status as an effective tool for weight management in adults with obesity and no diabetes. The magnitude of weight loss—nearly 12% greater than placebo—makes it one of the most promising non-surgical interventions available.

However, the risk-benefit balance must be carefully weighed. For patients at higher risk of gastrointestinal or hepatic complications, close monitoring or alternative treatments may be advisable.

These insights are crucial for endocrinologists, primary care physicians, and obesity specialists looking to tailor weight-loss plans based on patient-specific risks and goals.

Conclusion: A Potent Yet Watchful Approach to Obesity Management

Tan et al.’s meta-analysis supports the use of subcutaneous semaglutide in non-diabetic individuals with obesity, delivering impressive weight-loss outcomes. Nevertheless, the increased incidence of adverse events—particularly those involving the gastrointestinal and hepatobiliary systems—warrants vigilant clinical oversight.

For carefully selected patients, semaglutide offers a powerful and non-invasive alternative in the fight against obesity. Ongoing research will help clarify long-term safety and support broader clinical implementation.

References

1. Tan HC, Dampil OA, Marquez MM. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. J ASEAN Fed Endocr Soc. 2022;37(2):65-72. 
2. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. 
3. Garvey WT, Batterham RL, Bhatta M, et al. Two-Year Effects of Semaglutide in Adults with Overweight or Obesity: The STEP 5 Trial. Nat Med. 2022;28(10):2083–2091. 
4. Lin F, Yu B, Ling B, et al. Weight loss efficiency and safety of tirzepatide: A Systematic review. PLoS One. 2023;18(5):e0285197. 
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