Favorable long-term cardiovascular safety profile of linagliptin in type 2 diabetes
medwireNews: Findings from the CARMELINA trial suggest that the dipeptidyl peptidase-4 inhibitor linagliptin has a similar cardiovascular safety profile to placebo when added to standard care in high-risk type 2 diabetes patients.
The results add “important new evidence for type 2 diabetes patients at high risk of heart and/or kidney disease, a population that has been underrepresented in other cardiovascular outcome trials, but whom we see in our daily practice,” said investigator Bernard Zinman (University of Toronto, Ontario, Canada) in a press release.
All CARMELINA participants had a high risk for cardiovascular events, defined as either having macrovascular disease or albuminuria, or having impaired kidney function and/or albuminuria. A total of 57% of patients had established cardiovascular disease, while 74% had prevalent chronic kidney disease, and 33% had both conditions.
And more than 60% of participants had an estimated glomerular filtration rate (eGFR) below 60 ml/min per 1.73 m2, compared with 9–30% of patients in the SAVOR TIMI, EXAMINE, and TECOS trials, Zinman told delegates at the 54th EASD Annual Meeting in Berlin, Germany.
The composite endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke over a median follow-up of 2.1 years occurred in 12.4% of 3494 patients who were randomly assigned to receive linagliptin 5 mg once daily in addition to standard care, and in a comparable 12.1% of 3485 patients given add-on placebo.
The corresponding incidence of the composite endpoint was 5.77 and 5.63 per 100 patient–years, giving a nonsignificant hazard ratio of 1.02. Similarly, rates of all-cause mortality, as well as hospitalization for heart failure, were similar between the two groups.
The CARMELINA trial also investigated the renal safety profile of linagliptin, finding that the composite endpoint of end-stage renal disease, death due to kidney disease, or a sustained decrease in eGFR from baseline of at least 40% relative to placebo occurred in a comparable 9.4% of participants in the linagliptin group and 8.8% of those given placebo. However, linagliptin reduced albuminuria progression by a significant 14%.
The adverse events (AEs) that occurred during the trial were consistent with the known safety profile of linagliptin, said the investigators. Overall rates of AEs and serious AEs were similar between the linagliptin and placebo groups (77.2 vs 78.1% and 37.0 vs 38.5%, respectively), but rates of acute pancreatitis (0.3 vs 0.1%) and pemphigoid events (0.2 vs 0.0%) were numerically higher in the linagliptin group.
Commenting on the CARMELINA results, Philip Home (Newcastle University, UK) said that the trial “establishes the safety of linagliptin in very high risk people with diabetes in the medium-term.”
He believes that longer-term safety studies, carried out over 5–10 years, should be conducted for glucose-lowering agents, and recommended that superiority studies should be performed over longer durations in order to identify time-dependent treatment effects.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group