Januvia, a widely used diabetes drug that generates $6 billion in annual sales for maker Merck, does not increase patients’ risk of being hospitalized for heart failure, a risk that did show up in clinical trials of competing drugs.
“We’ve teased this data backwards and forwards and everything comes up looking like the drug does not have a cardiovascular safety signal,” Eric Peterson, a Duke University cardiologist who co-led the study, told a press conference at the annual meeting of the American Diabetes Association in Boston.
The results are being presented at the ADA meeting and published online in the New England Journal of Medicine.
Introduced in 2006, Januvia became Merck’s top seller after a rival drug from Novartis failed to be approved in the U.S. It’s popular because it is low in side effects, making it an easy drug for doctors to turn to control blood sugar early in treatment. It took other drug companies years to come up with competing drugs that, like Januvia, work by blocking an enzyme called dipeptidyl peptidase-4 (DPP-4). AstraZeneca’s Onglyza was launched in 2009, and now generates $820 million in annual sales. Takeda’s Nesina was introduced in 2013.
But Merck may have caught a big break when large studies of those drugs showed that they might increase the risk of heart failure. In a study called SAVOR, patients on Onglyza were 27% more likely to be hospitalized for heart failure, translating to an extra 0.6% of patients being hospitalized at 12 months. Patients taking Nesina had a slightly elevated risk of heart failure, thought the difference wasn’t significant. In April, a panel of advisors to the Food and Drug Administration voted that the drugs’ labels should carry warnings of the risk.
Januvia, however, doesn’t show any hint of the risk at all. In the trial being published today, called TECOS, 14,671 patients were randomly assigned to get either Januvia or placebo. Doctors were allowed to add other diabetes treatments in order to get the patients’ blood sugar under control.
Patients on Januvia had glycated hemoglobin, a measure of blood sugar, -0.29 percentage points lower. There was no difference at all between rates of heart problems, including cardiovascular death, heart attack, stroke, or hospitalization for chest pain, between the two groups. Likewise, rates of heart failure were exactly the same between the two groups. “Anything more positive would be a miracle in this high risk population,” says Martin Haluzik, of the 1st Faculty of Medicine in Prague, Czech Republic.
Haluzik says that the results show that heart failure isn’t a side effect for all DPP-4 drugs. Sanjay Kaul, a cardiologist at Cedars Sinai Medical Center, says that he believes that the “most likely explanation for the heart failure signal” with Onglyza is the play of chance. He notes that a big trial of Galvus, the Novartis drug that was never approved in the U.S., did not show a heart failure risk.
One rare problem that does come up in all the studies is a risk of acute pancreatitis, a severe inflammation of the pancreas. This happened in an extra 0.2% of patients on Nesina, an extra .02% of patients on Onglyza, and an extra 0.1% of patients on Januvia.
“The rate is so low that it is not hugely interesting,” says Ethan J. Weiss, a cardiologist at UCSF. His bigger concern: as with most blood-sugar lowering drugs, there is no evidence that Januvia is preventing heart attacks or strokes, which it had been hoped would be one of the long-term results of treating diabetes. He says his conclusion is he wouldn’t prescribe Januvia, but he also wouldn’t tell his patients to stop it if another doctor had prescribed it.
But even if he won’t prescribe it, others will. No diabetes drug has been shown to prevent heart attacks or strokes. But patients who got Januvia instead of placebo were less likely to have to use insulin or other diabetes drugs with more side effects. It’s likely that Merck’s $6 billion franchise just got some protection – and that it is going to get even bigger with time. Bernstein Research forecasts Januvia sales will hit $7.1 billion in three years.