Rates of major adverse cardiovascular events and mortality with basal insulin by liraglutide use: a DEVOTE sub-analysis


BACKGROUND AND AIMS: Cardiovascular (CV) safety profiles for insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100) were established by the DEVOTE and ORIGIN trials. In the LEADER trial, the glucagon-like peptide-1 analogue liraglutide significantly reduced the risk of major adverse cardiovascular events (MACE; CV death, non-fatal myocardial infarction or non-fatal stroke) and mortality vs. placebo in patients with type 2 diabetes (T2D) and high CV risk. This post hoc analysis of DEVOTE compared associations between concomitant liraglutide vs. no liraglutide use and the risk of MACE and all-cause mortality in patients with T2D and high CV risk, independent of the basal insulin assigned.

MATERIALS AND METHODS: In DEVOTE, patients with T2D and high CV risk (n=7637) were randomised 1:1 to degludec or glargine U100. HRs for MACE and all-cause mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time in the trial, without interaction testing. Sensitivity analyses adjusted for baseline covariates included age, sex, smoking, T2D duration, CV risk, insulin therapy, race, BMI, HbA1c, LDL, HDL and liver/kidney function.

RESULTS: At baseline, 436 (5.7%) patients were on liraglutide: 187 (2.4%) started and 210 (2.7%) stopped liraglutide thereafter. Mean liraglutide exposure from randomisation was 731 days. Liraglutide use was associated with significantly lower HRs for MACE and all-cause mortality vs. no liraglutide use (Table). Multiple sensitivity analyses confirmed these results. There was no significant difference in the rate of severe hypoglycaemia with liraglutide use vs. no liraglutide use (HR: 0.79 [0.51; 1.24]95% CI). A similar result was obtained following adjustment for additional baseline covariates (HR: 0.89 [0.57; 1.40]95% CI). Mean total insulin doses were comparable for patients who received liraglutide at any time (0.9 ± 0.7 units/kg) and those who never received liraglutide (1.0 ± 0.8 units/kg).

CONCLUSIONS: In this post hoc analysis of DEVOTE, liraglutide use was associated with a lower MACE and all-cause mortality rate in basal insulin users providing additional support to the results from the LEADER trial.

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Ranthe MF, Brown-Frandsen K, Emerson SS, et al.