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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]

PMID: 30297350

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Project description:ObjectiveTo evaluate the association between statin use and risk of biliary tract cancers (BTC).DesignThis is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.ResultsWe included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).ConclusionCompared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.

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Dataset Information

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.

Publications

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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