Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink

Oct 10, 2018BMJ open

Risk of depression or self-harm linked to blood sugar medicines for type 2 diabetes

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Abstract

The incidence of depression or self-harm was 8.2 events per 1000 person-years for dipeptidyl peptidase-4 inhibitors compared to 11.7 for sulfonylureas.

In the dipeptidyl peptidase-4 inhibitor cohort, the incidence of depression or self-harm was lower compared to sulfonylureas.
In the glucagon-like peptide-1 receptor agonists cohort, the incidence of depression or self-harm was higher compared to sulfonylureas.
Neither incretin-based therapy was associated with a statistically significant change in the incidence of depression or self-harm compared to sulfonylureas.
Similar results were observed when comparing incretin-based therapies to other glucose-lowering agents such as insulin and thiazolidinediones.

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OBJECTIVES: To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents.

DESIGN: Population-based cohort study.

SETTING: Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).

PARTICIPANTS: Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with a prior history of depression, self-harm and other serious psychiatric conditions were excluded.

MAIN OUTCOME MEASURES: The primary study outcome comprised a composite of new-onset depression or self-harm. Unadjusted and adjusted Cox proportional hazards regression was used to quantify the association between incretin-based therapies and depression or self-harm. Deciles of High-Dimensional Propensity Scores and concurrent number of glucose-lowering agents were used to adjust for potential confounding.

RESULTS: We identified new users of 6206 DPP-4i and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7 events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person-years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively. Incretin-based therapies were not associated with an increased or decreased incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA-cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to 2.50). Consistent results were observed for other glucose-lowering comparators including insulin and thiazolidinediones.

CONCLUSIONS: Our findings suggest that the two incretin-based therapies are not associated with an increased or decreased risk of depression or self-harm.

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Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink

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