Diabetes drugs with cardiovascular benefits broaden cardiology’s turf

November 9, 2016|Clinical Endocrinology News

He said he prescribes empagliflozin to patients with type 2 diabetes if they are hospitalized for heart failure or as outpatients, and he targets it to patients diagnosed with heart failure – including heart failure with preserved ejection fraction – as well as to patients with other forms of cardiovascular disease, closely following the EMPA-REG enrollment criteria. It’s too early in the experience with empagliflozin to use it preferentially in diabetes patients without cardiovascular disease or patients who in any other way fall outside the enrollment criteria for EMPA-REG, he said.

“I am happy to consult with their endocrinologist, or I tell patients to discuss this treatment with their endocrinologist. If the endocrinologist prescribes empagliflozin, great; if not, I feel an obligation to provide the best care I can to my patients. This is not a hard medication to use. The safety profile is good. Treatment with empagliflozin obviously has renal-function considerations, but that’s true for many drugs. The biggest challenge is what is covered by the patient’s insurance. We often need preauthorization.

“So far I have seen excellent responses in patients for both metabolic control and clinical responses in patients with heart failure. Their symptoms seem to improve,” said Dr. Fonarow, professor of medicine and co-chief of cardiology at the University of Southern California , Los Angeles.

While Dr. Fonarow cautioned that he also would not start empagliflozin in a patient with a HbA_1c below 7%, he would seriously consider swapping out a patient’s drug for empagliflozin if it were a sulfonylurea or a dipeptidyl peptidase-4 inhibitor. He stopped short of suggesting a substitution of empagliflozin for metformin. In Dr. Fonarow’s opinion, the evidence for empagliflozin is also “more robust” than it has been for liraglutide or semaglutide. With what’s now known about the clinical impact of these drugs, he foresees a time when a combination between a SGLT-2 inhibitor, with its effect on heart failure, and a GLP-1 analogue, with its effect on atherosclerotic disease, may seem an ideal initial drug pairing for patients with type 2 diabetes and significant cardiovascular disease risk, with metformin relegated to a second-line role.

Other cardiologists endorsed a more collaborative approach to prescribing empagliflozin and liraglutide.

“Seeing the complexity of the landscape” with more than one drug now showing some sort of clear cardiovascular benefit, “it is critically important for cardiologists to collaborate with diabetologists and endocrinologists, as well as primary care physicians, to give care based on the best available data,” said Robert J. Mentz, MD, a cardiologist and heart failure specialist at Duke University in Durham, N.C., who was an EMPA-REG investigator. “It should be collaborative to personalize the care as best we can, working together to get patients on the right drugs that improve outcomes and not just lower HbA_1c. I see these collaborations happening now, but much more needs to be done.”

Another team-approach advocate is Robert O. Bonow, MD, cardiologist and professor of medicine at Northwestern University in Chicago. “Cardiologists are comfortable prescribing metformin and telling patients about lifestyle, but when it comes to newer antidiabetic drugs, that’s a new field, and a team approach may be best,” he said in an interview. “If possible, a cardiologist should have a friendly partnership with a diabetologist or endocrinologist who is expert in treating diabetes.” Many cardiologists now work in and for hospitals, and easy access to an endocrinologist is probably available, he noted.

Other cardiologists suggested even more restraint. “We’re hopeful that the benefits of empagliflozin will translate info practice, but we are not yet sure whom to treat,” and the EMPA-REG results “need further validation,” said Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine and chief of cardiology at the VA Medical Center in Houston. “My preference is to use empagliflozin [only] in patients at risk for heart failure. We’ve been burned before” with harm from new treatments for patients with established heart failure, she warned during a talk at the Heart Failure Society of America meeting.

But new analyses of the EMPA-REG data reported by Dr. Fitchett at the ESC congress showed that empagliflozin treatment exerted a similar benefit of reduced cardiovascular death regardless of whether patients had prevalent heart failure at entry into the study, incident heart failure during follow-up, or no heart failure of any sort.

Impact of heart failure in EMPA-REG

Roughly 10% of the 7,020 patients enrolled in EMPA-REG had heart failure at the time they entered the trial. During a median follow-up of just over 3 years, the incidence of new-onset heart failure – tallied as either a new heart failure hospitalization or a clinical episode deemed to be heart failure by an investigator – occurred in 4.6% of patients on empagliflozin and in 6.5% of patients in the placebo arm, a 1.9-percentage-point difference and a 30% relative risk reduction linked with empagliflozin use, Dr. Fitchett reported.