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Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register
Univ Gothenburg, Dept Med, Gothenburg, Sweden.;Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden..
Ctr Registers Reg Vastra Gotaland, Gothenburg, Sweden..
Ctr Registers Reg Vastra Gotaland, Gothenburg, Sweden..
Ctr Registers Reg Vastra Gotaland, Gothenburg, Sweden..
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2016 (English)In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 18, no 10, 990-998 p.Article in journal (Refereed) Published
Abstract [en]

Aim: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Research design and methods: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Results: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was similar to 60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. Conclusions: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.

Place, publisher, year, edition, pages
2016. Vol. 18, no 10, 990-998 p.
Keyword [en]
cardiovascular complications, glucose-lowering agents, metformin, pharmacoepidemiology, type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-305306DOI: 10.1111/dom.12704ISI: 000383381000005PubMedID: 27282621OAI: oai:DiVA.org:uu-305306DiVA: diva2:1037778
Funder
Swedish Association of Local Authorities and Regions
Available from: 2016-10-18 Created: 2016-10-14 Last updated: 2016-10-18Bibliographically approved

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