Primary endpoint met in safety study with DPP-4 inhibitor
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News - June 9, 2015Treatment with sitagliptin, a DPP-4 inhibitor, versus placebo for median 3 years in 14,671 patients with type 2 diabetes (T2DM) and established cardiovascular (CV) disease showed non-inferiority for the primary composite cardiovascular endpoint of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), and no increase in hospitalization for heart failure in the sitagliptin group.
Researchers at the University of Oxford Diabetes Trials Unit (DTU) and the Duke Clinical Research Institute (DCRI) have found that among patients with T2DM and established CV disease, addition of sitagliptin to usual care did not impact on the risk for major adverse CV events, hospitalization for heart failure or adverse events.
In the study, similar control of blood glucose was aimed for both treatment arms, in order to be able to asses the effect of sitagliptin CV disease independently of its glucose-lowering effects. The utility of sitagliptin as a glucose-lowering agent was confirmed by the more frequent initiation of insulin therapy and the greater need for additional antihyperglycemic agents in the placebo group compared with the sitagliptin group.
The primary endpoint was time to first occurrence of cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke, hospitalisation for unstable angina (PP analyse HR: 0.98, 95%CI: 0.88-1.09, P<0.001), ITT HR: 0.99, 95%CI: 0.89-1.10, P=0.84). No increase in hospitalisation for heart failure was seen with sitagliptin (HR: 1.00, 95%CI: 0.83-1.20, P=0.983). Severe hypoglycaemia occurred at similar rates in both treatment groups (sitagliptine vs. placebo: 2.2% vs. 1.9%, ITT HR: 1.12, 95%CI: 0.89-1.40, P=0.33). All-cause mortality was comparable between groups (7.5% vs. 7.3%, ITT HR: 1.01, 95%CI: 0.90-1.14, P=0.88).
Results for the primary composite endpoint were consistent in almost all prespecified subgroup analyses, except for a difference in effect for patients with a BMI smaller vs. larger than 30 kg/m2.
Concerns about possible links between incretin-based therapies and effects on the pancreas have been raised. In TECOS, acute pancreatitis and pancreatic cancer were uncommon and not statistically significant different between groups. Numerically, in the sitagliptin group there were more patients with acute pancreatitis (0.23% vs. 0.2%, ITT HR: 1.93, 95%CI: 0.96-3.88, P=0.065) and fewer patients with pancreatic cancer than in the placebo group (0.1% vs. 0.2%, ITT HR: 0.66, 95%CI: 0.28-1.51, P=0.32).
Professor Rury Holman of Oxford University, Joint Chair of the study, commented ‘TECOS provides reassurance that sitagliptin may be used safely to improve blood glucose levels in a diverse group of T2DM patients at high cardiovascular risk without impacting on rates of cardiovascular complications or heart failure’.
Press release American Diabetes Association Scientific Sessions June 8 2015
The TECOS results were published in New England Journal of Medicine on June 8.
Researchers at the University of Oxford Diabetes Trials Unit (DTU) and the Duke Clinical Research Institute (DCRI) have found that among patients with T2DM and established CV disease, addition of sitagliptin to usual care did not impact on the risk for major adverse CV events, hospitalization for heart failure or adverse events.
In the study, similar control of blood glucose was aimed for both treatment arms, in order to be able to asses the effect of sitagliptin CV disease independently of its glucose-lowering effects. The utility of sitagliptin as a glucose-lowering agent was confirmed by the more frequent initiation of insulin therapy and the greater need for additional antihyperglycemic agents in the placebo group compared with the sitagliptin group.
The primary endpoint was time to first occurrence of cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke, hospitalisation for unstable angina (PP analyse HR: 0.98, 95%CI: 0.88-1.09, P<0.001), ITT HR: 0.99, 95%CI: 0.89-1.10, P=0.84). No increase in hospitalisation for heart failure was seen with sitagliptin (HR: 1.00, 95%CI: 0.83-1.20, P=0.983). Severe hypoglycaemia occurred at similar rates in both treatment groups (sitagliptine vs. placebo: 2.2% vs. 1.9%, ITT HR: 1.12, 95%CI: 0.89-1.40, P=0.33). All-cause mortality was comparable between groups (7.5% vs. 7.3%, ITT HR: 1.01, 95%CI: 0.90-1.14, P=0.88).
Results for the primary composite endpoint were consistent in almost all prespecified subgroup analyses, except for a difference in effect for patients with a BMI smaller vs. larger than 30 kg/m2.
Concerns about possible links between incretin-based therapies and effects on the pancreas have been raised. In TECOS, acute pancreatitis and pancreatic cancer were uncommon and not statistically significant different between groups. Numerically, in the sitagliptin group there were more patients with acute pancreatitis (0.23% vs. 0.2%, ITT HR: 1.93, 95%CI: 0.96-3.88, P=0.065) and fewer patients with pancreatic cancer than in the placebo group (0.1% vs. 0.2%, ITT HR: 0.66, 95%CI: 0.28-1.51, P=0.32).
Professor Rury Holman of Oxford University, Joint Chair of the study, commented ‘TECOS provides reassurance that sitagliptin may be used safely to improve blood glucose levels in a diverse group of T2DM patients at high cardiovascular risk without impacting on rates of cardiovascular complications or heart failure’.
Press release American Diabetes Association Scientific Sessions June 8 2015
The TECOS results were published in New England Journal of Medicine on June 8.
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