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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.

Abstract：

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.

journal_name

BMJ Open

journal_title

BMJ open

authors

Gamble JM,Chibrikov E,Midodzi WK,Twells LK,Majumdar SR

doi

10.1136/bmjopen-2018-023830

subject

Has Abstract

pub_date

2018-10-08 00:00:00

pages

e023830

issue

issn

2044-6055

pii

bmjopen-2018-023830

journal_volume

pub_type

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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.