- Adults with type 2 diabetes (T2D) and high risk for cardiovascular disease (CVD) and chronic kidney disease (CKD) see no increased risk for either with linagliptin (e.g., Tradjenta) vs placebo.
Why this matters
- Linagliptin is a selective dipeptidyl peptidase 4 inhibitor, a drug class showing cardiovascular safety in previous trials.
- Those trials did not, however, include patients at high CVD, renal risk.
- Primary outcome (CVD composite) in 12.4% with linagliptin (5.77/100 person-years) vs 12.1% with placebo (5.63/100 person-years):
- Absolute incidence rate difference, 0.13 (95% CI, −0.63 to 0.90) per 100 person-years;
- HR, 1.02 (95% CI, 0.89-1.17); and
- P<.001 for noninferiority.>
- Secondary outcome, composite kidney disease, in 9.4% with linagliptin (4.89/100 person-years) vs 8.8% on placebo (4.66/100 person-years):
- Absolute incidence rate difference, 0.22 (95% CI, −0.52 to 0.97) per 100 person-years;
- HR, 1.04 (95% CI, 0.89-1.22); and
- Adverse events:
- 77.2% linagliptin;
- 78.1% placebo.
- Death, heart failure hospitalization also did not differ.
- Randomized controlled trial (RCT; CARMELINA), August 2013-2016; 605 clinics, 27 countries.
- Linagliptin 5 mg/day (n=3494) vs placebo (n=3485); median follow-up, 2.2 years.
- Outcomes: CVD composite (primary); renal outcome composite (secondary).
- Funding: Boehringer Ingelheim; Eli Lilly.
- Better glycemic control on study drug.
- Short duration.