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. 2019 Feb;21(2):312-320.
doi: 10.1111/dom.13525. Epub 2018 Oct 11.

Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population-based, propensity-score-matched cohort study

Shihchen Kuo  1 , Chun-Ting Yang  2 , Jin-Shang Wu  3   4 , Huang-Tz Ou  2   5   6
Affiliations

Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population-based, propensity-score-matched cohort study

Shihchen Kuo et al. Diabetes Obes Metab. 2019 Feb.

Abstract

Aims: To compare the effects of initiating insulin as a fourth-line antidiabetic therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure.

Materials and methods: We conducted a nationwide population-based, retrospective cohort study involving 1022 (without prevalent diabetes-related complications [PDRCs]) and 2077 (with/without PDRCs) propensity score-matched pairs of fourth-line insulin therapy users and enhanced OAD therapy users identified in the period 2004 to 2010. Clinical outcomes including a composite cardiovascular outcome (myocardial infarction, stroke, heart failure or ischaemic heart disease), peripheral vascular disease (PVD), hypoglycaemia and all-cause mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to consider its potential effect on study outcomes.

Results: In a T2DM cohort without PDRCs, fourth-line insulin therapy was not associated with greater risks of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02-2.07), compared with enhanced OAD therapy. Among patients with T2DM with/without PDRCs, fourth-line insulin therapy was associated with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03-1.46), heart failure (HR 1.59, 95% CI 1.12-2.25), ischaemic heart disease (HR 1.37, 95% CI 1.09-1.73), PVD (HR 1.17, 95% CI 1.00-1.36), hypoglycaemia (HR 1.49, 95% CI 1.20-1.85) and all-cause mortality (HR 1.48, 95% CI 1.01-2.17), but adjustment for hypoglycaemia significantly attenuated the risk of heart failure (HR 1.34, 95% CI 0.92-1.94), PVD (HR 1.15, 95% CI 0.98-1.34) and all-cause mortality (HR 1.30, 95% CI 0.84-1.99).

Conclusions: Initiation of fourth-line insulin therapy can be considered for patients with T2DM with triple OAD therapy failure, and the importance of awareness and prevention of hypoglycaemia among insulin-treated patients with T2DM cannot be overstated.

Keywords: antidiabetic drug; cardiovascular disease; cohort study; hypoglycaemia; insulin therapy; type 2 diabetes.

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Conflict of interest statement

Conflicts of Interest

None reported.

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References

    1. Lingvay I, Kaloyanova PF, Adams-Huet B, Salinas K, Raskin P. Insulin as Initial Therapy in Type 2 Diabetes. J Investig Med. 2007;55(2):62–68. - PubMed
    1. Harrison LB, Adams-Huet B, Raskin P, Lingvay I. β-cell function preservation after 3.5 years of intensive diabetes therapy. Diabetes Care. 2012;35(7):1406–1412. - PMC - PubMed
    1. Weng J, Li Y, Xu W, et al. Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008;371(9626):1753–1760. - PubMed
    1. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes. Diabetes Care. 2013;36(11):3411–3417. - PMC - PubMed
    1. Lin SD, Tsai ST, Tu ST, et al. Glycosylated hemoglobin level and number of oral antidiabetic drugs predict whether or not glycemic target is achieved in insulin-requiring type 2 diabetes. Prim Care Diabetes. 2015;9(2):135–141. - PubMed

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