Linagliptin does not increase (or decrease) risk of adverse CVD outcomes

Reference

Rosenstock J, Perkovic V, Johansen OE, et al, for the CARMELINA Investigators. 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 2018. Nov 9. doi: 10.1001/jama.2018.18269. [Epub ahead of print]

Synopsis

These investigators identified adults (n = 6991) with type 2 diabetes (hemoglobin A1c values: 6.5% - 10.0%; 48 - 86 mmol/mol) and high cardiovascular and renal risk. High cardiovascular risk was defined as a history of coronary artery disease, stroke, or peripheral vascular disease. High renal risk was defined as either an estimated glomerular filtration rate (eGFR) of 45 to 75 mL/min/1.73 m2 and a urinary albumin to creatinine ratio (UACR) higher than 200 mg/g, or an eGFR of 15 to 45 mL/min/1.73 m2 regardless of UACR. Eligible patients randomly received (concealed allocation assignment) linagliptin (5 mg daily) or matching placebo. The primary outcome was the combined occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. An independent committee reviewed study outcomes and complete follow-up occurred for 98.7% of patients at a median of 2.2 years. Using intention-to-treat analysis, no significant differences in the primary outcome occurred in the linagliptin versus control group (12.4% vs 12.1%, respectively). Similarly, no significant group differences occurred in the secondary outcomes of end-stage renal disease, all-cause mortality, or hospitalization for heart failure. Reports of pancreatic cancer were nonsignificantly increased in the linagliptin group compared with the placebo group (11 vs 4, respectively).