Linagliptin and Cardiovascular Events in Patients With Type 2 Diabetes

In adults with type 2 diabetes (T2D), along with high cardiovascular (CV) risk and renal risk, linagliptin added to usual care “resulted in a noninferior risk of a composite CV outcome over a median of 2.2 years,” according to results published in JAMA.

Increased CV risk is known to accompany the onset of T2D, making it important to assess the effects of T2D treatments such as linagliptin on CV events. Lead author Julio Rosenstock noted that “prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease.”

The team’s objective then was to evaluate linagliptin’s effects on CV and kidney outcomes in patients with T2D.

In this placebo-controlled, randomized multicenter noninferiority trial, Rosenstock and colleagues collected data on adults with T2D (glycated hemoglobin of 6.5%-10%) and high CV and renal risk. The participants were treated at 605 clinic sites across 27 countries from 2013 to 2016. The 6979 enrollees in the program (average age, 65.9 years) received ≥1 dose of either linagliptin or placebo, and 98.7% of enrollees completed the treatment.

“Patients were [randomly assigned] to receive linagliptin, 5 mg once daily (n=3494), or placebo once daily (n=3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines.”

Patients with end-stage renal disease were excluded from this study.

Investigators found that “during a median follow-up of 2.2 years, the primary outcome occurred in 434 (12.4%) and 420 (12.1%) in the linagliptin and placebo groups, respectively” (P <.001 for noninferiority). The kidney outcome occurred in 9.4% of linagliptin treatments and 8.8% of placebo treatments (P =.62). Adverse events occurred in 2697 (77.2%) of patients who received linagliptin and in 2723 (78.1%) patients who received placebo; 29.7% of the linagliptin group and 29.4% of the placebo group had ≥1 hypoglycemia episode. Thus, there is “no significant difference between the linagliptin and placebo groups in the risk of heart failure hospitalization.”

This study also does not indicate any positive effects of linagliptin for composite kidney outcomes. The researchers noted that “this is likely a reflection of the reduced access to an available armamentarium of glucose-lowering therapies due to label restrictions for patients with low [epidermal growth factor receptor].”

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Reference

Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321(1):69-79.