Effects of Linagliptin on Cardiovascular Outcomes in T2D and Kidney Disease

Treatment with linagliptin in patients with type 2 diabetes and cardiovascular and/or kidney disease had no impact on risk for cardiovascular or kidney events.

Treatment with linagliptin in patients with type 2 diabetes (T2D) and cardiovascular and/or kidney disease had no impact on risk for cardiovascular or kidney events or hospitalization for heart failure, according to results of the CARMELINA study (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus) presented at the 28th Annual Congress of the American Association of Clinical Endocrinologists, held April 24 to 28, 2019, in Los Angeles, California.

While dipeptidyl peptidase-4 inhibitors have been investigated in cardiovascular outcome trials, only a small number of participants in these trials have had chronic kidney disease. For that reason, there are limited data regarding renal outcomes in this population.

Researchers in the CARMELINA study randomly assigned patients to receive treatment with linagliptin or placebo. The primary outcome of this double-blind study was 3-point major adverse cardiovascular events. The researchers also analyzed secondary kidney end points, including end-stage kidney disease, renal death, or sustained ≥40% decrease in estimated glomerular filtration rate (eGFR).

The study cohort included 6979 patients (mean age, 65.9 years) from 605 centers across 27 countries. The mean eGFR of the study participants was 54.6 mL/min/1.73 m2. Treatment with linagliptin lasted for a median of 2.2 years.

Treatment with linagliptin was associated with reduced glycated hemoglobin (HbA1c) compared with placebo (average difference for linagliptin vs placebo using least square means, -0.36%; 95% CI, -0.42 to -0.29). Results were similar in patients with eGFR <45 mL/min/1.73 m2 (-0.35%; 95% CI, -0.45 to -0.25) and eGFR ≥45 mL/min/1.73 m2 (-0.36%; 95% CI, -0.45 to -0.28).

Although HbA1c was significantly reduced with linagliptin, there was no difference in incidence of hypoglycemia. Furthermore, initiation or intensification of insulin treatment was less common in patients treated with linagliptin compared with placebo (hazard ratio [HR], 0.75; 95% CI, 0.65-0.81), with similar results for patients with eGFR <45 mL/min/1.73 m2 (HR 0.69; 95% CI, 0.59-0.81) or eGFR ≥45 mL/min/1.73 m2 (HR 0.76; 95% CI, 0.65-0.88).

With regard to the primary outcome, the researchers reported no difference between linagliptin- or placebo-treated patients in risk for adverse cardiovascular events. In addition, there was no difference between the 2 groups in risk for hospitalization for heart failure or in the secondary kidney end point.

The researchers concluded that linagliptin did not affect cardiovascular or kidney risk in participants with T2D and concomitant cardiovascular and/or kidney disease. “Significant reductions in HbA1c and insulin need was observed regardless of eGFR,” wrote the investigators.


Toto R, Perkovic V, Johansen OE, et al. Effect of linagliptin on cardiovascular and kidney outcomes in patients with type 2 diabetes and kidney disease: CARMELINA®. Presented at: American Association of Clinical Endocrinologists 28th Annual Scientific & Clinical Congress; April 24-28, 2019; Los Angeles, CA.

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This article originally appeared on Endocrinology Advisor