Abstract

The study investigated the impact of insulin glargine exposure on cardiovascular mortality in type 2 diabetes patients with incident insulin initiation. All consecutive diabetes patients aged >40 years were screened at their first diabetes outpatient visit between 01/01/2001 and 12/31/2008 (n = 79869). Exclusion criteria restricted the cohort to 4990 incident insulin users, aged 40–79 years, who were followed up for death until 12/31/2011. Baseline was defined 6 months after insulin initiation. Adjusted time-dependent competing risk regression analysis was performed. Mean baseline age was 62 ± 9 years, with mean follow-up of 4.7 ± 1.9 years. During 23179 person-years of exposure time, there were 887 deaths (521 cardiovascular). Glargine cumulative time exposure significantly lowered overall cardiovascular, subhazard ratio (SHR) 0.963 (CI 95% 0.944–0.981, p < 0.001), and myocardial infarction mortality, SHR 0.945 (CI 95% 0.899–0.994, p = 0.028), but not stroke mortality. Glargine cumulative dose exposure (10,000 IU increments) significantly lowered cardiovascular mortality, SHR 0.977 (CI 95% 0.960–0.993, p = 0.006), but not for myocardial infarction and stroke. Both cumulative dose and time exposure to insulin glargine were associated with lower cardiovascular mortality. The effect was mostly driven by myocardial infarction end point, supporting the concept of macrovascular benefit for basal analogue insulin use in type 2 diabetes.

Highlights

  • Several studies indicated that type 2 diabetes (T2D) significantly reduces life expectancy [1, 2], mainly as a consequence of increased rates of cardiovascular events [3]

  • The study investigated the impact of insulin glargine exposure on cardiovascular mortality in type 2 diabetes patients with incident insulin initiation

  • For the purpose of this observational study we focused on T2D patients treated only with oral antidiabetic drugs (OADs) at screening, who maintained OADs only for at least six months

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Summary

Introduction

Several studies indicated that type 2 diabetes (T2D) significantly reduces life expectancy [1, 2], mainly as a consequence of increased rates of cardiovascular events [3]. It was repeatedly shown that cardiovascular disease is the main cause of death among patients with diabetes mellitus, leading to a threefold increase in cardiovascular mortality [4]. Despite being used for almost 100 years, exogenous insulin is still surrounded by controversy regarding its effect on atherosclerosis risk and consequent CV events [6]. Diabetes being a progressive disease, the percentage of T2D patients using insulin increases in parallel with the duration of the disease [7, 8]. The ORIGIN trial showed that insulin glargine has no effect on cardiovascular events rate in subjects with early dysglycemia [9]. There are scarce data regarding its effect on cardiovascular mortality in subjects with long standing T2D

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