Wow! Maybe– Finally– A Positive Diabetes Drug Outcomes Trial

Until now the best thing anyone could say for sure about all the new diabetes drugs was that at least they didn’t kill people. That’s because although these drugs have been shown to be highly effective in reducing glucose levels, a series of large cardiovascular outcomes trials failed to provide any evidence of significant clinical benefit.

Now that may finally have changed. Boehringer Ingelheim and Eli Lilly announced today that the EMPA-REG OUTCOME trial showed that empagliflozin (Jardiance) successfully cut the rate of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke when compared to placebo in well-treated patients with type 2 diabetes. The companies announced the top line results today in a press release. More complete results will be presented on September 17 at the annual meeting of the  European Association for the Study of Diabetes Annual Meeting in Stockholm, Sweden. The companies also said that the safety profile of their drug “was consistent with previous studies.”

The trial randomized more than 7,000 patients with type 2 diabetes to empagliflozin (10mg or 25mg once daily) or placebo in addition to standard care with other diabetes and cardiovascular drugs. For more background on the trial see this rationale, design, and baseline characteristics paper.

Previous trials of diabetes drugs that failed to show clinical benefit include the TECOS trial with sitagliptin (Januvia), the SAVOR-TIMI 53 with saxagliptin (Onglyza), and the EXAMINE trial with alogliptin (Nesina). All these drugs are DPP-4 inhibitors. Empagliflozin is a member of the SGLT2 class of diabetes drugs. Analysts have speculated that outcomes trials with GLP-1 inhibitors may also be positive, though the first such trial, ELIXA, with lixisenatide, was only able to show that it did not cause harm.

One financial analyst, Timothy Anderson, described the positive outcome of the trial as “a holy grail of sorts that could give the drug – and the broader SGLT2 class in which it competes – a competitive leg up.” He speculated that the clinical benefit in the trial may be due to the modest body weight and blood pressure lowering effect of the drug.

In a series of tweets this morning Harlan Krumholz pointed out that although we “may finally have a glucose-lowering agent that reduces CV risk,” he urged caution until the full results are presented and validated. He also raised the provocative question: “What’s more amazing:#diabetes drug that lowers CV risk; or that it would be 1st diabetes drug to show that benefit?”