Rosenstock J, et al. - In patients with type 2 diabetes at high risk of cardiovascular (CV) and kidney events, investigators assessed the impact of linagliptin—a selective dipeptidyl peptidase 4 (DPP-4) inhibitor— on CV and kidney outcomes. A noninferior risk of a composite CV outcome over a median 2.2 years resulted with linagliptin added to usual care vs placebo added to usual care in this study population.

Methods

• Experts conducted this randomized, placebo-controlled, multicenter noninferiority trial from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes and a hemoglobin A1c of 6.5% to 10.0%, high CV risk, and high renal risk.
• They excluded those with end-stage renal disease (ESRD).
• Final follow-up occurred on January 18, 2018.
• They randomized the patients to receive linagliptin 5 mg once daily (n=3,494) or placebo once daily (n=3,485) added to usual care.
• Based on clinical need and local clinical guidelines, other glucose-lowering medications or insulin could be added.
• Time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke was the primary outcome.
• They defined the criteria for noninferiority of linagliptin vs placebo by the upper limit of the 2-sided 95% CI for the HR of linagliptin relative to placebo being < 1.3.
• Time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained ≥ 40% decrease in eGFR from baseline were included in the secondary outcome.

Results

• Of 6,991 enrollees, ≥ 1 dose of study medication was received by 6,979, and 98.7% completed the study.
• The primary outcome, during a median follow-up of 2.2 years, occurred in 12.4% and 12.1% in the linagliptin and placebo groups, respectively.
• Findings suggested the occurrence of kidney outcome in 9.4% and 8.8%, respectively.
• In 2,697 (77.2%) and 2,723 (78.1%) patients in the linagliptin and placebo groups, adverse events occurred; ≥ 1 episodes of hypoglycemia were observed in 1,036 (29.7%) and 1,024 (29.4%) patients; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis.