Comparison of injectable dulaglutide (Trulicity) versus oral semaglutide (Rybelsus) for weight loss?

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Last updated: February 17, 2025View editorial policy

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From the Guidelines

Weight Loss Comparison

Injectable dulaglutide (Trulicity) and oral semaglutide (Rybelsus) are both effective for weight loss, but oral semaglutide (Rybelsus) 2.4mg daily has demonstrated greater efficacy, with a mean weight loss of 10-15% from baseline, compared to dulaglutide 3.0mg weekly, which has resulted in a mean weight reduction of 6-10% from baseline 1.

  • The efficacy of semaglutide is supported by the STEP trials, which showed significant weight loss with semaglutide treatment, with a mean weight loss of 14.9% and 16.0% at 68 weeks in the STEP 1 and STEP 3 trials, respectively 1.
  • In contrast, dulaglutide has been shown to result in significant weight loss, but to a lesser extent, with a mean weight reduction of 6-10% from baseline 1.
  • It is essential to note that long-term use of semaglutide is necessary to maintain weight loss, as significant weight regain was observed after cessation of treatment in the STEP trials 1.
  • Both dulaglutide and semaglutide have been shown to decrease the risk of cardiovascular events in adults with overweight or obesity without diabetes 1.
  • The choice between injectable dulaglutide and oral semaglutide should be based on individual patient factors, including preference, cost, and availability, as well as the presence of any comorbidities that may influence the choice of treatment.

From the Research

Comparison of Injectable Dulaglutide (Trulicity) versus Oral Semaglutide (Rybelsus) for Weight Loss

  • The available studies do not directly compare injectable dulaglutide (Trulicity) with oral semaglutide (Rybelsus) for weight loss. However, some studies provide information on the efficacy of these medications for weight loss:
    • A study on dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in patients with type 2 diabetes found that dulaglutide 4.5 mg provided superior weight loss compared to 1.5 mg 2.
    • A review of high-dose once-weekly semaglutide for chronic weight management found that it offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors 3.
    • An indirect treatment comparison of semaglutide 2.0 mg versus dulaglutide 3.0 mg and 4.5 mg found that semaglutide 2.0 mg significantly reduced body weight compared to dulaglutide 3.0 mg and 4.5 mg 4.
    • A randomized, double-blind, double-dummy, placebo-controlled trial of semaglutide 2.4 mg once a week in adults with overweight or obesity and type 2 diabetes found that semaglutide 2.4 mg achieved a superior and clinically meaningful decrease in body weight compared to placebo 5.

Efficacy of Dulaglutide and Semaglutide for Weight Loss

  • Dulaglutide 4.5 mg has been shown to provide superior weight loss compared to dulaglutide 1.5 mg in patients with type 2 diabetes 2.
  • Semaglutide 2.0 mg has been shown to significantly reduce body weight compared to dulaglutide 3.0 mg and 4.5 mg in an indirect treatment comparison 4.
  • Semaglutide 2.4 mg has been shown to achieve a superior and clinically meaningful decrease in body weight compared to placebo in adults with overweight or obesity and type 2 diabetes 5.

Safety and Tolerability of Dulaglutide and Semaglutide

  • Common adverse events associated with dulaglutide include nausea and vomiting 2.
  • Gastrointestinal adverse events, which were mostly mild to moderate, were reported in patients treated with semaglutide 2.4 mg and 1.0 mg 5.

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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