Noninferior CV Outcomes for Linagliptin in T2D With High CV, Renal Risk

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Linagliptin is a selective, once-daily DPP-4 inhibitor approved for glycemic management in patients with type 2 diabetes.
Linagliptin is a selective, once-daily DPP-4 inhibitor approved for glycemic management in patients with type 2 diabetes.

In adults with type 2 diabetes (T2D) and elevated cardiovascular and renal risk, adding dipeptidyl peptidase-4 inhibitor linagliptin to usual care did not significantly change the risk for composite cardiovascular or renal outcomes, according to study results published in JAMA.

Preliminary phase 3 data indicated possible renal and cardiovascular benefits of treatment with linagliptin. To evaluate the effect of linagliptin on cardiovascular and kidney outcomes in individuals with T2D, researchers followed 6991 patients with T2D as part of the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin Trial. Patients had hemoglobin A1c levels between 6.5% to 10.0%, high cardiovascular risk (history of vascular disease and urine-albumin creatinine ratio >30 mg/g), and high renal risk (estimated glomerular filtration rate of 15 to 45 mL/min/1.73 m2 or 45 to 75 mL/min/1.73 m2 plus urine-albumin creatinine ratio ≥200 mg/g). Individuals were randomly assigned to the linagliptin group (5 mg) or a matching placebo group. 

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Primary cardiovascular outcomes included the time until cardiovascular death, myocardial infarction that did not cause death, or stroke that did not result in death. Secondary renal outcomes included time to death by renal failure, a composite of end-stage renal disease, or a consistent reduction in estimated glomerular filtration rate of ≥40%.

During a median follow-up of 2.2 years, the primary cardiovascular outcome occurred in 434 of 3494 participants in the linagliptin group and 420 of 3485 participants in the placebo group (P <.001 for noninferiority). The kidney outcome occurred in 327 participants in the linagliptin group and in 306 participants in the placebo group (hazard ratio, 1.04; P =.62).

Among adults with T2D and high cardiovascular and renal risk, researchers concluded “linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk [for] a composite [cardiovascular] outcome over a median 2.2 years." The results also did not indicate any benefit of linagliptin for kidney outcomes.

Multiple authors declared affiliations with pharmaceutical companies. See reference for a full list of disclosures.

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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 [published online November 9, 2018]. JAMA. doi:10.1001/jama.2018.18269

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