TOPLINE:

A post hoc analysis of the SURMOUNT-1, -3, and -4 trials showed that tirzepatide was associated with significant weight reductions in adults with overweight or obesity who initiated weight-inducing (WI) medications during the studies, with weight loss comparable to that observed in the overall trial populations.

METHODOLOGY:

• Obesity-related comorbidities are often managed with WI medications such as corticosteroids, selective beta-1 blockers, antidepressants, antipsychotics, and sulfonylureas, but their impact on current obesity therapies remains unclear.
• Researchers conducted a post hoc analysis of the phase 3 SURMOUNT-1, -3, and -4 trials to evaluate weight loss with tirzepatide in adults with overweight or obesity without type 2 diabetes who initiated concomitant WI medications.
• Participants were required to initiate at least one WI medication during the study; nonsteroidal WI medications had to be taken for at least 3 months and oral corticosteroids for at least 1 week.
• The mean percentage change in body weight from baseline to week 72 (SURMOUNT-1 and SURMOUNT-3) or week 88 (SURMOUNT-4) was assessed.

TAKEAWAY:

• The WI subgroups included 442 participants from SURMOUNT-1 (mean age, 48.0 years; 73.5% female), 100 from SURMOUNT-3 (mean age, 49.5 years; 75.0% female), and 134 from SURMOUNT-4 (mean age, 51.8 years; 67.9% female) who received either tirzepatide or a placebo.
• Most participants in the WI subgroups received one nonsteroidal WI medication (72.9% in SURMOUNT-1, 68.0% in SURMOUNT-3, and 64.9% in SURMOUNT-4).
• In SURMOUNT-1, tirzepatide produced dose-dependent, statistically significant mean loss compared with placebo from baseline to week 72: -13.3% (5 mg), -20.5% (10 mg), and -21.3% (15 mg; P < .001 for all).
• At the maximum tolerated dose, tirzepatide produced mean weight differences compared with placebo of -26.1% in SURMOUNT-3 (week 72) and -18.6% in SURMOUNT-4 (week 88; P < .001 for both).
• Mean weight reductions with tirzepatide were comparable to those observed in the overall SURMOUNT populations, including both WI users and nonusers.

IN PRACTICE:

“By understanding the potential association of WI medications with the effectiveness of obesity management medications such as tirzepatide, clinicians can make informed decisions and tailor treatment plans to better meet the needs of their patients,” the authors of the study wrote.

SOURCE:

The study was led by Rodolfo J. Galindo, MD, University of Miami Miller School of Medicine, Miami. It was published online in JAMA Network Open.

LIMITATIONS:

The analysis was post hoc, and exclusion of participants with type 2 diabetes may have limited generalizability. Reliance on self-reported medication use and variations in WI drug type, duration, and dose may have introduced bias. Because WI medications were initiated after study entry, exposure periods were shorter than the overall treatment duration, potentially underestimating their impact on weight.

DISCLOSURES:

The SURMOUNT trials were funded by Eli Lilly and Company. Five authors reported being employees of Eli Lilly and Company and holding stock in the company. Some authors disclosed receiving personal fees, grants, nonfinancial support, and travel funding from various pharmaceutical companies, including Eli Lilly and Company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.