The incidence of cardiovascular events in patients with type 2 diabetes treated with the DPP-4 inhibitor sitagliptin (Januvia) is significantly lower than in those treated with sulphonylureas, show reveals from a pooled analysis reported this week at the International Diabetes Federation 2011 World Diabetes Congress (4 December 2011).
The analysis pooled results from three double-blind studies, each randomising patients to sitagliptin (100mg/day; n=1,226) or a sulphonylurea (n=1,225). These agents were added to ongoing metformin therapy in two of the studies, while the third was a monotherapy trial. The cumulative patient exposure was 1,269 patient years in patients treated with sitagliptin and 1,274 patient years in the sulphonylurea group.
Results of a post-hoc cardiovascular safety analysis reported at the congress showed no patients treated with sitagliptin had a major adverse cardiovascular events, while 11 patients on a sulphonylurea had at least one reported event. This gave an incidence rate of 0 per 100 patient years for sitagliptin compared to 0.9 per 100 patient years for the sulphonylurea-treated patients (between group difference -0.9%, 95% confidence interval -1.6, -0.5). The incidence of cardiovascular-related death was also lower with sitagliptin (0 per 100 patient years) compared to patients treated with sulphonylureas (0.4 per 100 patient years).
The lead researcher, Dr Barry Goldstein, Vice President for Clinical Research in Diabetes and Endocrinology with Merck Sharp and Dohme, Rahway, USA, explained the rationale for reviewing the data with sitagliptin compared to sulphonylureas:
“Sulphonylureas have potentially deleterious cellular effects on the cardiovascular system and have been shown to increase the risk of cardiovascular events in some studies. So, we analysed the incidence of cardiovascular events in trials comparing sitagliptin to sulphonylureas in patients with type 2 diabetes.”
Dr Goldstein continued:
“Although the numbers were small, we found no major adverse cardiovascular events with sitagliptin compared to 11 with sulphonylureas. This suggests something is going on here – is it that sulphonylureas are, in fact, causing more events, or sitagliptin is causing fewer, or a combination of the two?”
He considered the results are important but noted the limitations of a retrospective pooled analysis and suggested that prospective studies are needed to explore this further. However, he pointed out that a recent analysis of 19 trials with sitagliptin showed no increase in risk of cardiovascular events compared to placebo or other medicines.
The effect of sitagliptin on cardiovascular outcomes is currently being evaluated prospectively in the randomised, placebo-controlled TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) study. This will compare the impact of adding sitagliptin as part of usual care to treatment without sitagliptin on cardiovascular outcomes in 14 000 patients with type 2 diabetes and cardiovascular disease. Patients will be followed-up for a minimum of three years and results are expected in 2015.
Written by: Susan Mayor PhD, freelance medical journalist, London, UK