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Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the CARMELINA randomized trial

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posted on 04.06.2020 by Vlado Perkovic, Robert Toto, Mark E Cooper, Johannes FE Mann, Julio Rosenstock, Darren K McGuire, Steven E Kahn, Nikolaus Marx, John H Alexander, Bernard Zinman, Egon Pfarr, Sven Schnaidt, Thomas Meinicke, Maximillian von Eynatten, Jyothis T George, Odd Erik Johansen, Christoph Wanner, CARMELINA® investigators
Objective

Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular and kidney outcomes across baseline eGFR categories (≥ 60, 45-<60, 30-<45 and < 30 ml/min/1.73 m2) in CARMELINA, a cardio-renal placebo-controlled outcome trial of the DPP-4 inhibitor linagliptin (NCT01897532).

Research Design and Methods

Participants with cardiovascular disease (CVD) and/or CKD were included. The primary outcome was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with a secondary outcome renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other endpoints included progression of albuminuria, change in HbA1c and adverse events (AEs) including hypoglycemia.

Results

6979 subjects (mean age 65.9 years, eGFR 54.6 ml/min/1.73m2, 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared to placebo did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction p-values > 0.05). Regardless of eGFR, albuminuria-progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced between groups overall and across eGFR categories.

Conclusions

Across all GFR categories, in participants with type 2 diabetes and CKD and/or CVD, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c, and no difference in AEs was observed.

Funding

This study was sponsored by Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance.

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