In the EXAMINE study, alogliptin did not cause a significant increase in heart failure hospitalization, was effective at lowering HbA1c and safe regarding pancreatic health, according to experts at EASD 2013.
This double blind study compared 5,380 patients randomly assigned to placebo with standard of care or alogliptin (Nesina, Takeda Pharmaceuticals). The primary endpoint was a composite of first occurrence of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.
“Due the media and the questions that have been asked in the last 3 weeks of me, my steering committee and the sponsor, we actually analyzed a post-hoc, non-specified evaluation of the EXAMINE study, in which we at least removed the confounding of death,” William B. White, MD, of the Calhoun Cardiology Center, University of Connecticut School of Medicine, said during his presentation. “In none of the analyses, regardless of how they were constructed, did we see a significant difference in any of our endpoints.”
William B. White
Researchers used a standard heart failure composite (all-cause mortality, nonfatal MI, nonfatal stroke, urgent revascularization due to unstable angina, heart failure hospitalization) typically used in heart failure trials looking at CV mortality and hospitalization for heart failure.
With adjudication, they found a composite of 7.4% in the alogliptin group and 7.5% in the placebo group (HR=0.98, P=.976). Looking at CV mortality alone, the HR was 0.84 (P=.207), and in hospitalization for heart failure, which also considered those occurring after the primary endpoint, the HR was 1.19 (P=.22).
Although the overall study excluded patients with unstable CV conditions, of those hospitalized, 15% had a history of congestive heart failure. Of patients with a history of heart failure, 18% of alogliptin patients vs. 22% on placebo met a primary endpoint in this post-hoc analysis.
In a press conference, Simon R. Heller, DM, FRCP, of the University of Sheffield in the United Kingdom, confirmed White’s data and addressed other concerns of the endocrinology audience.
“There was a modest, but consistently lower HbA1c in those receiving alogliptin throughout the trial,” Heller said. The recently published study showed a –0.36% mean difference between the alogliptin group and the placebo group.
He said severe hypoglycemia was “uncommon” and was confined to patients assigned insulin or sulfonylurea, besides their study treatment.
Lastly, he said there was no risk for cancer, including pancreatic cancer.
“It’s an important message that, until a few years ago, the various authorities around the world were saying HbA1c of 7%, even down to 6.5%, and we just moved away from that thanks to these and other data,” Heller said. “This just adds to the evidence that we should be individualizing therapy, discussing it with our patients. They also have a choice to make and it’s a legitimate contribution.”
For more information:
White WB. Both presented at: 49th Annual Meeting of the European Association for the Study of Diabetes; Sept. 24-27, 2013; Barcelona, Spain.
Disclosure: White and Heller report relationships with various pharmaceutical and device companies.