Aleglitazar Does Not Reduce Risk of Recurrent CV Events among Diabetes Patients

The use of aleglitazar does not appear to reduce the risk of cardiovascular events in diabetic patient…. 

According to results from a phase III study released to the Journal of the American Medical Association following a presentation at the 2014 American College of Cardiology Scientific Sessions, aleglitazar does not appear to reduce recurrent cardiovascular events in diabetic patients.

In a prior phase II studies, aleglitazar demonstrated efficacy, significantly reducing HbA1c, triglycerides, LDL cholesterol, and increasing HDL.

In the AleCardio trial, researchers randomized 7,226 diabetic patients to receive 150 mcg aleglitazar or placebo daily.

A total of 6.3% of patients were either lost to follow-up or had withdrawn consent. Although aleglitazar decreased HbA1c and improved cholesterol profiles, it failed to decrease the time to cardiovascular death, nonfatal heart attack and nonfatal stroke – with these primary endpoints occurring in 9.5% of aleglitazar group and 10% in the placebo group (HR 0.96 [95% CI, 0.83 to 1.11]; P = 0.57).

Researchers also found Aleglitazar to be associated with an increased risk of hypoglycemia, bone fractures, renal abnormalities and gastrointestinal bleeding.

Due to adverse events and an apparent lack of efficacy, this trial was terminated early.

Roche has terminated development of aleglitazar due to safety concerns about the late-stage diabetes treatment. The Swiss major said that following the results of a regular review of a Phase III trial of aleglitazar, an independent data and safety monitoring board has recommended the study be halted "due to safety signals and lack of efficacy." Based on the recommendation, Roche has decided to terminate that trial and all other studies involving aleglitazar.

• In phase II studies, aleglitazar displayed efficacy for lowering blood glucose and promoting a favorable cholesterol profile
• In this phase III trial, aleglitazar appeared to have no benefit for reducing cardiovascular risk
• The use of aleglitazar was associated with a high incidence of adverse events, including an increased risk of fractures, hypoglycemia, renal abnormalities and gastrointestinal bleeding

Lincoff AM, Tardif JC, Schwartz GG, et al. Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus: The AleCardio Randomized Clinical Trial. JAMA. 2014