Obese patients taking antidepressants lost weight on semaglutide

Presenter: Robert F. Kushner, MD, Professor, Departments of Medicine and Medical Education, Northwestern University Feinberg School

Kushner RF, Fink-Jensen A, Frenkel O, et al. Semaglutide 2.4 mg in people with or without antidepressants at baseline: a post-hoc analysis. Presentation at Obesity Week, October 14–17, 2023, Abstract Oral-068.

Obese patients taking antidepressants lost as much weight on semaglutide as those not on antidepressants in a post-hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) trials.1 Those taking antidepressants lost an average 11% to 19% of body weight across 4 trials in the STEP program,2–5 reported presenter Robert F. Kushner, MD, Professor, Departments of Medicine and Medical Education, Northwestern University Feinberg School at the 2023 Obesity Week annual meeting.

Several antidepressants have been reported to induce weight gain, increasing the risk of obesity-related illnesses such as diabetes mellitus, hypertension, and coronary heart disease.6

The STEP program was designed to test semaglutide 2.4 mg/week specifically for promoting weight loss:

  • The double-blind STEP 1 trial2 enrolled 1,961 adults with a body mass index of 30 kg/m2 or greater or at least 27 kg/m2 with at least 1 weight-related complication without diabetes. They received either 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention.
  • The STEP 2 trial3 assessed once-a-week subcutaneous semaglutide 2.4 mg versus semaglutide 1.0 mg (the dose approved for diabetes treatment) and placebo for weight management in 1,210 adults with overweight or obesity, and type 2 diabetes.
  • STEP 34 included 611 adults with overweight or obesity who received 68 weeks of treatment with once-weekly subcutaneous semaglutide vs placebo, combined with intensive behavioral therapy.
  • STEP 55 assessed once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) over 2 years treatment of 304 adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes.

In all 4 trials, participants were excluded if they had major depressive disorder within 2 years before screening or a Patient Health Questionnaire-9 score of 15 or higher on a scale of 0 (not depressed) to 27 (severely depressed) at screening. Patients taking antidepressants for other conditions were included. Overall, 539 participants were on antidepressants at baseline across all 4 trials.

The current analysis of the STEP program examined the effects of semaglutide 2.4 mg on weight loss efficacy and safety according to participants’ baseline antidepressant use. Efficacy was assessed by body weight change from baseline to week 68, and safety was assessed by adverse events.

“In all 4 trials, body weight change from baseline to week 68 was significant and clinically meaningful regardless of baseline antidepressant use for semaglutide vs placebo,” said Dr. Kushner.

Average weight losses in STEP 1:

  • 15.7% with semaglutide plus antidepressants
  • 14.7% with semaglutide without antidepressants
  • 0.2% with placebo plus antidepressants
  • 2.8% with placebo without antidepressants.

Average weight losses in STEP 2:

  • 10.7% with semaglutide plus antidepressants
  • 9.5% with semaglutide without antidepressants
  • 3.3% with placebo plus antidepressants
  • 3.4% with placebo without antidepressants.

Average weight losses in STEP 3:

  • 16.2% with semaglutide plus antidepressants
  • 15.9% with semaglutide without antidepressants
  • 5% with placebo plus antidepressants
  • 5.9% with placebo without antidepressants.

Average weight losses in STEP 5:

  • 19% with semaglutide plus antidepressants
  • 14.1% with semaglutide without antidepressants
  • 1.6% weight gain with placebo plus antidepressants
  • 4% weight loss with placebo without antidepressants.

Dr. Kushner noted that in all 4 trials not all interaction tests were significant in participants receiving semaglutide with antidepressants at baseline vs those without.

Adverse event rates with semaglutide were higher for those on antidepressants at baseline. In the 4 trials, 97.6% to 100% of participants taking antidepressants reported adverse events compared with 86.7% to 95.3% of participants not taking them. Among placebo groups, adverse event rates were also higher for those on antidepressants (88.4% to 100%) than those who did not take antidepressants (77.2% to 95.8%).

Dr. Kushner concluded: “Across the STEP program, participants who were on antidepressants at baseline and prescribed semaglutide 2.4 mg achieved significant weight loss versus placebo with limited impact on adverse events. Results were comparable to those who were not on antidepressants at baseline.”

References

  1. Kushner RF, Fink-Jensen A, Frenkel O, et al. Semaglutide 2.4 mg in people with or without antidepressants at baseline: a post-hoc analysis. Presentation at Obesity Week, October 14–17, 2023, Abstract Oral-068.
  2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021; 384:989–1002 doi:10.1056/NEJMoa2032183
  3. Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021; 397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0
  4. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 randomized clinical trial. JAMA 2021; 325(14):1403–1413. doi:10.1001/jama.2021.1831
  5. Garvey WT, Batterham RL, Bhatta M et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med 2022; 28:2083–2091. doi:10.1038/s41591-022-02026-4
  6. Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 2010; 71(10):1259–1272. doi:10.4088/JCP.09r05346blu

Disclosures

Kushner is an advisor for Novo Nordisk, Lilly, and WW, and a consultant for Pfizer, Altimmune, and Boehringer Ingelheim.

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