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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.

SUBMITTER: Gamble JM 

PROVIDER: S-EPMC6194463 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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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.

Gamble John-Michael JM   Chibrikov Eugene E   Midodzi William K WK   Twells Laurie K LK   Majumdar Sumit R SR  

BMJ open 20181008 10


<h4>Objectives</h4>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.<h4>Design</h4>Population-based cohort study.<h4>Setting</h4>Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).<h4>Participants</h4>Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidy  ...[more]

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