Physicians' Academy for Cardiovascular Education

DPP-4 inhibitor non-inferior to placebo in preventing CV outcomes

Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk

Literature - Rosenstock J, Perkovic V, Johansen OE et al. - J Am Med Assoc 2018; published online ahead of print

Introduction and methods

Linagliptin is a selective, once-daily, dipeptidyl peptidase 4 (DPP-4) inhibitor, indicated for glucose-lowering in patients with type 2 diabetes (T2DM), and it has been hypothesized that linagliptin therapy may also provide cardiovascular (CV) and renal protection to T2DM patients [1,2]. The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) [3] tested this hypothesis by evaluating the CV and renal safety of linagliptin in adult T2DM patients at high cardiorenal risk. Participants with end-stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73 m2 or requiring maintenance dialysis, were excluded.

CARMELINA, a randomized, double-blind, placebo-controlled clinical trial, randomized eligible individuals 1:1 to receive either oral linagliptin (5 mg/day) or placebo, on top of standard of care. The primary endpoint was the time to first occurrence of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (3-point major adverse CV event [MACE]). The secondary endpoint was the time to first occurrence of a composite of ESRD, death due to renal failure, or a sustained decrease of at least 40% in eGFR from baseline.

Main results


In adult T2DM patients at high cardiorenal risk, linagliptin on top of standard of care was non-inferior compared with placebo, with regard to the risk of CV outcomes, during a median observation time of 2.2 years. Renal outcomes were slightly more in the linagliptin group, however, this difference between groups was not statistically significant.


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