No additional threat of heart failure with Januvia in high-risk adults with type 2 diabetes
BOSTON – The DPP-IV inhibitor Januvia does not increase cardiovascular risk or benefit in adults with type 2 diabetes at high risk for acute cardiovascular events, according to study findings presented here.
In announcing results from the TECOS cardiovascular outcomes study, a worldwide randomized, double blind, placebo-controlled trial, researchers also found no increase in hospitalization for heart failure in patients assigned Januvia (sitagliptin, Merck) vs. placebo, while observing a small decrease in HbA1c levels.
“This is a glucose-lowering drug being tested for cardiovascular benefit or harm; the idea was not to see a glucose difference,” Rury R. Holman, FRCP, FMedSci, of the University of Oxford, and joint chairman of the TECOS study, said in a press conference announcing the findings.
Rury R. Holman
Patients were treated to similar HbA1c targets — a difference of less than 0.3% was observed at the end of the study — to ensure that cardiovascular outcomes were not influenced by a potential difference in HbA1c levels, Holman said.
“However, the utility of the drug is proven,” Holman said. “Because the number of people who got the active sitagliptin who needed additional anti-hyperglycemic agents or required insulin in normal clinical practice was substantially and significantly less. So the glucose-lowering part [of the drug] works, but the study was aimed at looking at the cardiovascular endpoints.”
Holman and colleagues at other institutions analyzed data from 14,671 adults from 673 sites in 38 countries with type 2 diabetes aged 50 years and older (mean age, 65 years; 29% women; 68% white; mean BMI 30.2 kg/m2), who had a prior history of CVD and an HbA1c level between 6.5% and 8%. The mean duration of diabetes was 11.6 years among participants; mean HbA1c was 7.2%; 18% of participants had a history of heart failure. The majority of patients were taking metformin (approximately 81%); nearly 25% were using insulin.
Participants were assigned either sitagliptin monotherapy; sitagliptin with metformin, sulfonylurea or pioglitazone; or insulin alone or in combination with metformin. Within the cohort, 7,332 were assigned sitagliptin 100 mg/day ; dose was lowered to 50 mg/day if patients had an estimated glomerular filtration rate (eGFR) between 30 and 50 mL/min/1.73 m2; 7,339 were assigned placebo. The dose was increased or decreased based on renal function assessed during usual care.
Researchers conducted follow-up in 4-month intervals during the first year of treatment, and then twice yearly (face-to-face visits and phone consultations) until 1,300 confirmed primary endpoints — CV death, nonfatal myocardial infarction (MI), nonfatal stroke or hospitalization for unstable angina — occurred.
Researchers found that the addition of sitagliptin to usual care did not affect the risk for major adverse CV events, hospitalization for heart failure or adverse events.
For the primary and secondary composite cardiovascular outcome, sitagliptin was noninferior, and not superior, for CV death, nonfatal MI, nonfatal stroke or hospitalization for unstable angina, with 11.4% of sitagliptin patients in the intent-to-treat population experiencing a primary cardiovascular event vs. 11.6% in the placebo group.
Incidents of hospitalization for heart failure were similar, with 3.1% of participants in each group (HR, 1.00; adjusted for a baseline history of heart failure).
“In this study, we specifically looked at the rates of heart failure events and found there were no differences — as a matter of fact, there was no hint of increased heart failure seen in the sitagliptin-treated patients relative to placebo,” Eric Peterson, MD, of the Duke Clinical Research Institute and joint chairman of the study, said in a press conference.
“Given the size of our study and the longer duration of follow-up, as well as the higher risk of our population, we feel this very adequately addresses the question and puts to bed the question — at least with sitagliptin — that there is any risk for heart failure increase with this drug,” Peterson said.
Researchers observed a very low rate of acute pancreatitis and pancreatic cancer in the study period. There were 23 events of acute pancreatitis in the sitagliptin group vs. 12 events for those assigned placebo, and fewer patients with pancreatic cancer (n = 9) than in the placebo group (n = 14), but the numbers were not statistically significant, according to researchers.
“There was no new data to suggest we should be overly concerned,” Holman said, referring to the drug’s effect on the pancreas.
Researchers observed no excess of severe hypoglycemia in the sitagliptin group (n = 160 vs. n = 143 for placebo). There were no differences in rates of infections or GI or metabolic conditions between the study groups.
. – Regina Schaffer
Reference: Green JB, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.
Disclosures: Green reports research funding from AstraZeneca, GlaxoSmithKline and Merck. Holman reports receiving research funding from AstraZeneca, Bayer and Merck, and honoraria from Amgen, Bayer, Elcelyx, GlaxoSmithKline and Janssen. Peterson reports receiving research funding from AstraZeneca, Daiichi Sankyo, Eli Lilly, Genentech and Janssen. Merck sponsored and funded the study.