Tirzepatide Effective for Weight Reduction Among Patients on Weight-Inducing Medications, Also: JAMA
USA: An analysis published in JAMA Network Open has revealed that tirzepatide produced significant weight loss in adults who were also taking weight-inducing medications such as corticosteroids and antidepressants. Importantly, the degree of weight loss was comparable to that seen in the overall trial population, even among participants without Type 2 diabetes.
The findings are based on a post hoc evaluation of data from three Phase 3 randomized clinical trials—SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4—conducted between 2019 and 2023. The analysis, led by Rodolfo J. Galindo from the University of Miami Miller School of Medicine and colleagues, specifically examined individuals with overweight or obesity who initiated one or more medications known to promote weight gain during the course of the trials.
Weight-inducing medications, including corticosteroids and certain antidepressants, are commonly prescribed and often complicate obesity management. Recognizing this, the investigators sought to determine whether tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, could still deliver meaningful weight reduction in such patients.
Across the three trials, approximately 17% to 20% of participants reported using at least one weight-inducing medication. The subgroup included 442 participants in SURMOUNT-1, 100 in SURMOUNT-3, and 134 in SURMOUNT-4. Most individuals were taking a single nonsteroidal weight-promoting drug, while a small proportion were on multiple such medications. The average duration of exposure to these medications ranged from about 51 to 58 weeks.
The analysis revealed the following findings:
- Tirzepatide showed substantial weight reduction despite the use of weight-inducing medications.
- In SURMOUNT-1, mean weight loss ranged from 13.3% (5 mg dose) to 21.3% (15 mg dose) over 72 weeks compared to placebo.
- In SURMOUNT-3, the maximum tolerated dose led to a 26.1% reduction in body weight over 72 weeks.
- In SURMOUNT-4, participants achieved an average weight loss of 18.6% over 88 weeks.
These outcomes closely mirrored the primary results observed in the overall trial populations, suggesting that the presence of weight-inducing medications did not substantially diminish the efficacy of tirzepatide. The consistency of weight loss across varying doses and study designs reinforces the drug’s potential utility in complex clinical scenarios.
The authors concluded that tirzepatide may offer an effective treatment option for individuals with overweight or obesity who require medications that typically promote weight gain. They emphasized that understanding how such concomitant therapies interact with anti-obesity treatments can help clinicians make more informed and individualized treatment decisions.
While the findings are encouraging, the researchers noted the need for further studies to explore the long-term impact of tirzepatide in diverse populations and to better understand the mechanisms underlying its effectiveness in the context of weight-inducing medications.
Reference:
Galindo RJ, Gudzune KA, Look M, et al. Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials. JAMA Netw Open. 2026;9(3):e263274. doi:10.1001/jamanetworkopen.2026.3274
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