Still, there were some questions about the data. The drug did not reduce the risk of heart attacks over all by a statistically significant amount, and it actually seemed to raise the risk of stroke, though not by a statistically significant amount.
So how did it reduce deaths from cardiovascular causes? One way, not necessarily expected, was by reducing deaths from heart failure, a condition in which the heart cannot pump enough blood.
Lilly and Boehringer announced last month that the drug had decreased cardiovascular problems among trial participants. But the data was not revealed until Thursday, when it was presented in Stockholm at the annual meeting of the European Association for the Study of Diabetes and alsopublished by The New England Journal of Medicine.
Tim Anderson, pharmaceutical analyst at Sanford C. Bernstein & Company, tripled his estimate of Jardiance sales in 2020 to $2.7 billion. Sales of two other drugs in the same class, known as SGLT2 inhibitors, might also increase even though there is no data yet showing that they decrease cardiovascular risk.
Those drugs are Invokana from Johnson & Johnson and Farxiga from AstraZeneca. The findings could hurt sales of some other types of diabetes drugs, including the Merck blockbuster Januvia.
Lilly’s shares rose nearly 7 percent Thursday, to $89.98. Boehringer is privately held.
The Food and Drug Administration approves diabetes drugs if they reduce blood sugar levels. It does not require that the drugs be shown to reduce the risks of the complications of high blood sugar, such as heart attacks, even though that is the real goal of treatment.
“The F.D.A. has given diabetes drugs a bye,” said Dr. David M. Nathan, director of the diabetes center at Massachusetts General Hospital. That is because some studies started decades ago suggested that controlling blood sugar did lower the risk of certain complications, like blindness and kidney disease.
But whether the drugs reduce heart attacks and other cardiovascular problems has been less clear. There was some evidence of benefit in the very long run shown in those early studies. But there have also been counterexamples, including one trial several years ago in which more intensive glucose control raised the risk of death.
In 2007, an analysis by Dr. Nissen suggested that the widely used diabetes drug Avandia increased the risk of heart attacks. While the finding was disputed, the F.D.A. began requiring developers of new diabetes drugs to conduct large trials to rule out the possibility that their drugs increased cardiovascular risk.
Several of those large studies have now been conducted, including one for Merck’s Januvia, and the drugs have generally been found not to raise cardiovascular risk. But they did not decrease the risks, either — until this trial with Jardiance.
The study, paid for by Lilly and Boehringer, involved 7,000 people with Type 2 diabetes who already had cardiovascular disease, so they were at very high risk of heart attacks and strokes. They were randomly assigned to get either Jardiance, which is known generically as empagliflozin, or a placebo. The patients were allowed to take other diabetes drugs as well.
After a median follow-up of about three years, about 10.5 percent of those getting Jardiance had suffered a heart attack or a stroke, or had died from cardiovascular causes, compared with 12.1 percent of those getting a placebo. That works out to about a 14 percent relative reduction in risk.
About 3.7 percent of those getting the drug died from cardiovascular causes compared with 5.9 percent of those taking the placebo pill, a relative risk reduction of 38 percent. There was also a 32 percent reduction of risk of death from all causes and a reduction of 35 percent for hospitalization for heart failure.
The authors of the study do not think Jardiance’s effect comes from its ability to reduce blood sugar, but perhaps from its ability to reduceblood pressure, weight and arterial stiffness.
Dr. Bernard Zinman, director of the diabetes center at Mount Sinai Hospital in Toronto and the principal investigator in the trial, said the results were particularly impressive because most of the patients were already taking statins and blood pressure drugs to reduce their cardiovascular risks. Dr. Zinman has been a consultant to Lilly and Boehringer.
Still, he and other experts stopped short of saying that Jardiance should now be the treatment of choice, though that might be looked at by committees that write guidelines. Most important, some experts said, the results of the study might not apply to the majority of people with Type 2 diabetes, who have a far lower risk of cardiovascular problems than the people in the trial.
Jardiance and other SGLT2 inhibitors, which work by causing sugar to be excreted in urine, have side effects like increased urinary tract and genital infections. Recently, the F.D.A. expressed concerns that one or all of those drugs might cause bone fractures and a dangerousacid buildup in the blood. In the Jardiance trial, however, those problems were not seen.
Jardiance, a daily pill, costs about $350 a month, according to the website GoodRx.
The results could bolster support for the F.D.A.’s policy of requiring large cardiovascular studies that aim to rule out risks for new diabetes drugs. Critics say these costly trials are unnecessary and deter companies from developing drugs for the 29 million Americans with diabetes.
One critic, Dr. Robert E. Ratner, chief scientific and medical officer for the American Diabetes Association, said he was not dissuaded. He said companies wanting to prove that their drugs reduce heart risk “have an intrinsic motive for pursuing such studies, and they will occur on their own without F.D.A. mandate.”
But Dr. Ratner said it was unfair and wasteful to single out diabetes for studies just to prove the absence of risk, without any initial reason to be concerned. He said that to date, 138,000 patients had been enrolled in such trials at a cost of at least $2 billion.