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Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia
Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
AstraZeneca Nordic Baltic, Sodertalje, Sweden..
Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
Statisticon AB, Uppsala, Sweden..
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2017 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 123, 199-208 p.Article in journal (Refereed) Published
Abstract [en]

Aims: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with insulin or DPP-4i after metformin monotherapy during 2007-2014 identified in the Swedish Prescribed Drug Register were followed for outcome in the Cause of Death and National Patient Registers. Insulin and DPP-4i patients were matched 1: 1 using propensity-score matching. Comparisons between groups were performed using unadjusted Cox regression models. Additionally, multivariate adjusted survival models were used to test the results using the full population without matching. Results: Of 27,767 mono-metformin-treated patients, 55.7% started insulin and 44.3% a DPP-4i, and after matching both groups had 9278 patients each. Median follow-up (patients years) times were 3.84 (37,578) and 3.93 (37,983) for insulin and DPP-4i-groups, respectively. Insulin compared with DPP-4i was associated with higher risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia; adjusted HR (95% CI): 1.69 (1.45-1.96); 1.39 (1.21-1.61); and 4.35 (2.26-8.35), respectively. When performing multivariate adjusted analyses on the full population similar results were found. Conclusions: Initiation of insulin, compared with DPP-4i treatment, was associated with an increased risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia. Results from randomized trials will be important to elucidate causal relationships.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2017. Vol. 123, 199-208 p.
Keyword [en]
Insulin, Type 2 diabetes, Dipeptidyl peptidase-4 inhibitor, Cardiovascular disease, Hypoglycemia, Outcome
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-319682DOI: 10.1016/j.diabres.2016.12.004ISI: 000393944700023PubMedID: 28056431OAI: oai:DiVA.org:uu-319682DiVA: diva2:1087457
Funder
AstraZeneca
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-04-07Bibliographically approved

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