Is weight loss with Semaglutide (Rybelsus) and Semaglutide (Ozempic) comparable?

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Last updated: April 14, 2025View editorial policy

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From the Guidelines

Weight loss with Rybelsus and Ozempic is not the same, with Ozempic typically producing more significant weight loss due to its higher bioavailability when injected. According to a recent study published in JAMA 1, subcutaneous semaglutide (Ozempic) has been shown to result in a mean weight loss of 14.9% to 16.0% at 68 weeks, whereas oral semaglutide (Rybelsus) has been associated with a mean weight loss of 15.1% at 68 weeks, but it's not yet FDA approved for obesity alone. The difference in weight loss between the two formulations can be attributed to the higher bioavailability of the injectable form, which delivers more medication directly into the bloodstream.

Key Differences

  • Ozempic (injectable semaglutide) has been shown to produce more significant weight loss, with a mean weight loss of 14.9% to 16.0% at 68 weeks 1
  • Rybelsus (oral semaglutide) has been associated with a mean weight loss of 15.1% at 68 weeks, but its approval for obesity alone is still pending 1
  • The injectable form of semaglutide has higher bioavailability, resulting in more effective weight loss

Administration Guidelines

  • Rybelsus must be taken on an empty stomach with no more than 4 ounces of water and nothing eaten for 30 minutes after
  • Ozempic requires weekly subcutaneous injection

Primary Indication

  • Both medications are primarily approved for type 2 diabetes management, with weight loss considered a beneficial side effect rather than their primary indication 1

From the FDA Drug Label

The exposure of semaglutide decreases with an increase in body weight. However, semaglutide doses of 0. 5 mg and 1 mg provide adequate systemic exposure over the body weight range of 40-198 kg evaluated in the clinical trials.

The FDA drug label does not answer the question.

From the Research

Weight Loss with Rybelsus and Ozempic

  • Rybelsus and Ozempic are both used for weight management, but they have different mechanisms of action and study results.
  • According to the study 2, semaglutide (the active ingredient in Ozempic) resulted in a mean change in body weight from baseline to week 68 of -14.9% compared to -2.4% with placebo.
  • Another study 3 reviews the data on semaglutide and states that it has demonstrated the largest weight loss of any obesity medication to date, with reductions of approximately 15% of initial weight at 68 weeks.
  • However, there is no direct comparison between Rybelsus and Ozempic in the provided studies.
  • A study 4 compares the cost-effectiveness of different antiobesity medications, including semaglutide, but does not mention Rybelsus.
  • Other studies 5 and 6 are not relevant to the comparison of Rybelsus and Ozempic for weight loss.

Comparison of Weight Loss

  • The available data suggests that semaglutide (Ozempic) is effective for weight loss, with significant reductions in body weight compared to placebo 2, 3.
  • However, without direct comparison studies, it is unclear whether Rybelsus and Ozempic have the same weight loss effects.
  • Further research is needed to determine the relative efficacy of Rybelsus and Ozempic for weight loss.

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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