Importance: Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications.
Objective: To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology.
Design, setting, and participants: This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously.
Interventions: Semaglutide, 2.4 mg, vs placebo.
Main outcomes and measures: Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated.
Results: This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5.
Conclusions and relevance: 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.
Trial registration: ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).
Importance: Historic redlining, the practice by the Home Owners' Loan Corporation (HOLC) of systematically denying credit to borrowers in neighborhoods that were inhabited by primarily African American individuals, has been associated with poor community outcomes, but the association with individual risk of death is not clear.
Objective: To examine if exposure to residential redlining practices by HOLC in 1940 is associated with increased risk of death later in life.
Design, setting, and participants: The study linked individuals who resided within HOLC-graded neighborhoods (defined as Census Enumeration Districts) in 1940 with administrative death records data. The study estimated hazard ratios as well as age-specific life expectancy gaps (at age 55, 65, and 75 years) for HOLC grading exposure. This was done using methods that adapted standard parametric survival analysis to data with limited mortality coverage windows and incomplete observations of survivors. The analysis sample consisted of 961 719 individual-level observations across 13 912 enumeration districts within 30 of the largest US cities (based on 1940 population counts) across 23 states. Data were analyzed between December 1, 2023, and September 4, 2024.
Main outcome and measures: The exposure was HOLC grade based on historic HOLC maps, with A representing "best" or creditworthy areas; B, "still desirable"; C, "definitely declining"; and D, "hazardous" areas not worthy of credit (ie, redlined), and the main outcome was age at death from the Social Security Numident file.
Results: The 961 719-person individual sample had a mean (SD) age of 19.26 (9.26) years in 1940 and a mean (SD) age at death of 76.83 (9.22) years. In a model adjusted for sex (52.48% female; 47.52% male), race and ethnicity (7.36% African American; 92.64% White), and latent place effects, a 1-unit lower HOLC grade was associated with an 8% (hazard ratio, 1.08 [95% CI, 1.07-1.09]) increased risk of death. At age 65 years, these hazard differentials translated into an estimated life expectancy gap of -0.49 (95% CI, -0.56 to -0.43) years for each 1-unit decrease of the HOLC grade.
Conclusion: This study found that individuals who resided within redlined neighborhoods in 1940 had lower life expectancy later in life than individuals who resided within other HOLC-graded areas.
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