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Antidiabetes agents and risk of incident depression in 686,522 people with type 2 diabetes mellitus: A 20-year population-based cohort study

Ho MTH, Chan JKN, Lo HKY, Fang CZ, Wong CSM, Lee KCK, Lai FTT, Ng APP et al.

Psychological medicine, 2026

686,522 participants

Abstract

Background: People with diabetes have increased risk of depression that further worsens clinical outcome. However, occurrence of depression among patients with diabetes exposed to antidiabetes agents is under-studied. We investigated whether antidiabetes agents would decrease the risk of depression in people with diabetes.

Methods: This population-based cohort study identified 686,522 patients with incident type-2 diabetes between 2002-2021 in Hong-Kong who were exposed to any antidiabetes agents, using territory-wide medical-record database of public-healthcare services. Associations of exposure to antidiabetes agents and risk of first-diagnosed depression were examined by Cox proportional-hazards models for each individual agent. An array of covariates, including age, sex, calendar-year period, catchment-area, pre-existing physical/psychiatric-comorbidities, average HbA1c-level, diabetic-complications, cardiovascular/lipid-lowering medications, and presence of other antidiabetes agents under investigation was adjusted. Three sets of sensitivity-analyses were conducted by (a) restricting to patients with cumulative drug-exposure ≥90 days and ≥180 days, (b) monotherapy, and (c) incorporating commonly-used non-antidiabetic medications as exposure variables.

Results: Lower risk of new-onset depression was associated with exposure to any antidiabetes agents (HR 0.42, 95%CI 0.39-0.45) compared with no exposure in patients with incident type-2 diabetes. Lower depression risk was…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 686,522 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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