Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials
Pooled result · PHQ-9 score (STEP 1, 2, 3)Result — go to the resultEstimated treatment difference −0.56 95% CI −0.81 to −0.32Authors' conclusion
The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care.
Study context
- Population
- Adults with overweight or obesity without known major psychopathology (STEP 2 participants also had T2D); STEP 1–3: 69.6% women, mean (SD) age 49 (13) years; STEP 5: 77.6% women, mean (SD) age 47 (11) years3,377 STEP 1–3
- Comparison
- Semaglutide 2.4 mg SC once weekly vs placebo
- Outcome
- Depressive symptoms (Patient Health Questionnaire (PHQ-9)) and suicidal ideation/behavior (Columbia-Suicide Severity Rating Scale)
Methodological detailsrandomized, double-blind, placebo-controlled, multicenter, phase 3a (STEP 1, 2, 3; 68 weeks), phase 3b (STEP 5; 104 weeks)
- Randomized
- Double-blind
- Placebo-controlled
- Multicenter
- Phase 3a (STEP 1, 2, 3; 68 weeks)
- Phase 3b (STEP 5; 104 weeks)
Pooled result
PHQ-9 score (STEP 1, 2, 3) · week 68
Estimated treatment difference
−0.56
95% CI −0.81 to −0.32
P < 0.001
By group
Semaglutide 2.4 mg
2.0
mean · SD 2.9
Placebo
2.4
mean · SD 3.3
As reported in the abstract
Further pooled results
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Shift to a more severe PHQ-9 depression category (STEP 1, 2, 3) · baseline to week 68 | 0.63 (0.50–0.79) | P < 0.001 | |
| 0.512Odds ratio (log scale) |
Mean
| Outcome | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Baseline PHQ-9 score (STEP 1, 2, 3)Indicating no/minimal symptoms of depression | 2.0 (SD 2.3) | 1.8 (SD 2.3) |
STEP 5 · 104 weeks
- Similar results were observed in STEP 5
Safety
- Psychiatric disorder adverse events generally balanced between groups
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →