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CV Outcomes in Study on Glycemia Reduction in Diabetes
Quick Takes
- Although CV event rates did not differ by individual treatment group; compared with the other groups combined, the liraglutide-treated group had a significantly lower risk of a composite CV outcome.
- Overall, these data suggest that liraglutide may reduce the risk of CV events in patients with diabetes considered at relatively low risk compared with treatment with other commonly used glucose-lowering medications.
Study Questions:
What are the cardiovascular (CV) outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin, in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study)?
Methods:
The investigators followed 5,047 participants with a mean ± standard deviation age of 57.2 ± 10.0 years, type 2 diabetes duration of 4.0 ± 2.7 years, and low baseline prevalence of CV disease (CVD) (myocardial infarction [MI], 5.1%; cerebrovascular accident, 2.0%) for a median of 5 years. Prespecified outcomes included between-group time-to-first event analyses of MACE-3 (composite of major adverse CV events: CV death, MI, and stroke), MACE-4 (MACE-3 + unstable angina requiring hospitalization or revascularization), MACE-5 (MACE-4 + coronary revascularization), MACE-6 (MACE-5 + hospitalization for heart failure [HFH]), and the individual components. MACE outcomes and HFH in the liraglutide-treated group were compared with the other groups combined using Cox proportional hazards models. MACE-6 was also analyzed as recurrent events using a proportional rate model to compare all treatment groups.
Results:
There were no statistically significant differences in the cumulative incidence of first MACE-3, MACE-4, MACE-5, or MACE-6, or their individual components, by randomized treatment group. However, when compared with the other treatment groups combined, the liraglutide-treated group had a significantly lower risk of MACE-5 (adjusted hazard ratio [aHR], 0.70; 95% confidence interval [CI], 0.54-0.91; p = 0.021), MACE-6 (aHR, 0.70; 95% CI, 0.55-0.90; p = 0.021), and HHF (aHR, 0.49; 95% CI, 0.28-0.86; p = 0.022). Compared with the liraglutide group, significantly higher rates of recurrent MACE-6 events occurred in the groups treated with glimepiride (rate ratio, 1.61; 95% CI, 1.13-2.29) or sitagliptin (rate ratio, 1.75; 95% CI, 1.24-2.48).
Conclusions:
The authors report that liraglutide treatment may reduce the risk of CV events in patients at relatively low risk compared with other commonly used glucose-lowering medications.
Perspective:
This study compared the effectiveness of four medications (sitagliptin, glimepiride, insulin glargine, and liraglutide) added to metformin in patients with type 2 diabetes largely without CVD. Although CV event rates did not differ by individual treatment group; when compared with the other groups combined, the liraglutide-treated group had a significantly lower risk of a composite CV outcome (MI, stroke, CV death, unstable angina, or coronary revascularization) with and without HHF. Overall, these data suggest that liraglutide may reduce the risk of CV events in patients with diabetes considered at relatively low risk compared with treatment with other commonly used glucose-lowering medications, similar to the benefit noted in patients with or at high risk for atherosclerotic CVD.
Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention
Keywords: Diabetes Mellitus, Type 2, Glucose
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