What Glucagon-like peptide-1 (GLP-1) receptor agonist medication is approved for weight loss in patients without a history of Diabetes Mellitus (DM)?

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Last updated: May 29, 2025View editorial policy

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From the Guidelines

Semaglutide (brand name Wegovy) is the most effective GLP-1 medication approved for weight loss in adults without diabetes, with a significant reduction in weight and improvement in weight-related comorbidities compared to other options 1. The medication is administered as a once-weekly subcutaneous injection, with a recommended dose that gradually increases over time: starting at 0.25 mg for the first month, then 0.5 mg for the second month, 1 mg for the third month, 1.7 mg for the fourth month, and finally reaching the maintenance dose of 2.4 mg. Some key points to consider when using semaglutide for weight loss include:

  • The medication works by mimicking the hormone GLP-1, which regulates appetite and food intake by acting on the brain's hunger centers, slowing gastric emptying, and increasing feelings of fullness 1.
  • Common side effects include nausea, vomiting, diarrhea, and constipation, which typically improve over time.
  • Semaglutide should be used alongside lifestyle modifications including diet and exercise for optimal results, and patients should stay well-hydrated and start with smaller, more frequent meals to minimize gastrointestinal side effects.
  • The SELECT study showed that semaglutide had a lower composite incidence of death due to cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke at 39.8 months, with a hazard ratio of 0.80 (95% CI, 0.72-0.90) 1. It's worth noting that while liraglutide is also an option for weight loss, semaglutide has been shown to be more effective in reducing weight and improving weight-related comorbidities, with a lower risk of gastrointestinal adverse events 1. Overall, semaglutide is a highly effective option for weight loss in adults without diabetes, with a strong evidence base supporting its use 1.

From the Research

GLP-1 Medication for Weight Loss

  • Semaglutide is a GLP-1 medication approved for weight loss without a history of diabetes, as indicated by studies 2, 3, 4, 5, 6.

Approval and Indication

  • The US Food and Drug Administration approved semaglutide injection at 2.4 mg once weekly for chronic weight management in adults with obesity or overweight with at least one weight-related condition 2.
  • Semaglutide is indicated for weight management in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater 2.

Efficacy and Safety

  • Semaglutide has demonstrated significant weight loss, with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risk factors and physical functioning 3, 6.
  • The most common adverse events with semaglutide were nausea and diarrhea, which were typically transient and mild-to-moderate in severity and subsided with time 3.
  • Semaglutide 2.4mg had the best weight loss, followed by liraglutide 3.0mg, semaglutide 1.0mg, and liraglutide 1.8mg, as shown in a systematic review and network meta-analysis 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

The New England journal of medicine, 2021

Research

Wegovy (semaglutide): a new weight loss drug for chronic weight management.

Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 2022

Research

Semaglutide for the treatment of obesity.

Trends in cardiovascular medicine, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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