Medical Technology

Inhibitors of SGLT2 in Primary Care: ‘All Hands on Deck’

Sodium glucose cotransporter-2 (SGLT2) inhibitors have been described as revolutionary advances in the management of patients with type 2 diabetes, particularly in people with comorbid cardiovascular and kidney disease.

But this relatively new class of drugs recently has made the leap into cardiology practice, with approvals by the US Food and Drug Administration (FDA) of dapagliflozin (Farxiga) and empagliflozin (Jardiance) for heart failure with reduced ejection fraction (HFrEF).

With multiple benefits proven in often overlapping diseases, SGLT2 inhibitors are now important tools for both general practitioners and specialists. But consistent implementation in heart failure remains a challenge, and it can be difficult to know which provider should initiate therapy in appropriate patients.

Experts told Medscape Medical News that primary care physicians can take the lead in identifying heart failure patients who would benefit from an SGLT2 inhibitor, or otherwise support the multidisciplinary care needed by the up to 22% of people with type 2 diabetes who develop heart failure.

PCPs: The Front Line in Heart Failure

SGLT2 inhibitors lower blood sugar concentrations by blocking the reabsorption of glucose by the kidneys. They also at least transiently increase urinary sodium excretion which along with a number of other mechanisms may provide benefits in heart failure

Mikhail Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City, and co-author of the DAPA-HF trial that led to FDA approval of dapagliflozin for HFrEF, said primary care is “absolutely critical” for effective implementation of SGLT2 inhibitors in heart failure, which will affect as many as one in five people in their lifetime.

Primary care doctors are key to effective prevention. They’re really the front line of defense for heart failure, diabetes, and chronic kidney disease.
Dr Mikhail Kosiborod

“Primary care doctors are key to effective prevention,” Kosiborod said. “They see the most patients who have not yet had a cardiovascular or kidney event, or those who don’t have access to specialty care. They’re really the front line of defense for prevention and, in many cases, for treatment of heart failure, diabetes, and chronic kidney disease.”

Implementation of the standard of care remains an important unmet need in patients with HFrEF. Now known as “quadruple therapy” with the addition of SGLT2 inhibitors — which cuts mortality risk by 73% over 2 years — the standard of care was previously known as “triple therapy,” a combination of an angiotensin-receptor neprilysin inhibitor (ARNI), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA). Prior research shows that fewer than 25% of patients eligible for triple therapy received it.

It often takes years for effective new therapies to reach patients after positive results of clinical trials and inclusion in practice guidelines. To help overcome clinical inertia in heart failure, Silvio Inzucchi, MD, clinical chief of the section of endocrinology at Yale University School of Medicine, New Haven, Connecticut, and a co-investigator on the DAPA-HF trial, recommended an “all hands on deck” approach.

“Every patient encounter, whether a primary care provider, a cardiologist, or an endocrinologist is an opportunity to improve care,” Inzucchi said. “If you are seeing a patient with heart failure that is not on an SGLT2 inhibitor, definitely consider starting so long as there are no prevailing contraindications, and keep their specialists in the loop.”

Kenny Lin, MD, MPH, professor of clinical family medicine at Georgetown University School of Medicine, Washington, DC, said PCPs are well equipped to prescribe SGLT2 inhibitors for heart failure in appropriate cases depending on the severity of disease.

“PCPs are perfectly capable of prescribing SGLT2 inhibitors in patients with stable heart failure who may see a cardiologist once or twice a year — or not at all,” Lin said. “On the other hand, in patients with unstable heart failure who have frequent exacerbations and hospitalizations, I would probably be more comfortable having cardiology managing this therapy since it’s a fairly recent addition to standard treatment for heart failure.”

Teamwork, Communication Key

Both generalists and specialists may have practical and safety concerns about initiating an SGLT2 inhibitor in patients with heart failure with and without type 2 diabetes. Experts agreed these concerns can be alleviated through good communication between providers.

A recent poll by the American College of Cardiology showed that the most common barrier cardiologists face in prescribing an SGLT2 inhibitor (29.8%) is the risk of hypoglycemia that can occur in patients with diabetes who also receive insulin or sulfonylurea. In this scenario, cardiologists and diabetes specialists can work together to adjust the dose of a patient’s existing diabetes regimen, if necessary.

“Just keep everyone in the loop,” Inzucchi said. “In those on insulin who are being followed by an endocrinologist, you may want to give them a heads-up so the insulin dose can be tweaked in those who are already tightly controlled. If there is a cardiologist or endocrinologist involved in their care, at the very least copy them on your assessment.”

Primary care physicians may also be better equipped to educate patients about genital hygiene to prevent genital yeast infections — a common side effect of SGLT2 inhibitors that usually occurs during early treatment — or treat one if it occurs.

Despite these safety issues, and rare potential complications such as diabetic ketoacidosis, primary care physicians should know that SGLT2 inhibitors are generally well tolerated and easy to prescribe, Kosiborod said.

“It’s one pill a day, there’s no need for dose titration, there aren’t really many drug-drug interactions to worry about, and they tend to be well-tolerated,” Kosiborod said. “So they’re about as easy to use as anything we’ve ever had in the heart failure armamentarium.”

Given the speed at which SGLT2 inhibitors work, with heart failure benefits accruing within just a few weeks in randomized trials, Kosiborod said lost time is an important consequence of each missed opportunity to initiate these therapies in appropriate patients to prevent disease progression.

“Heart failure patients are going to see various generalists and specialists, so the clinician who should be prescribing SGLT2 inhibitors is whoever has the opportunity to do so,” Kosiborod said. “Especially in heart failure, these agents have been shown to make patients live longer, feel better, and stay out of the hospital. There is an opportunity lost in terms of time when we wait unnecessarily to initiate these efficacious therapies.”

While continuing medical education focused on SGLT2 inhibitors for heart failure are just starting to target the primary care audience, Lin said he expects that primary care physicians will play a growing role in their implementation.

“I think primary care physicians will have questions about SGLT2 inhibitor selection and dosing for heart failure in patients without diabetes,” he said. “But I expect that as prescribing these drugs becomes increasingly mainstream, we will become as comfortable with them as prescribing diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and other commonly used heart failure drugs.”

Kosiborod and Inzucchi reported relationshps from multiple pharmaceutical companies. Lin reported no relevant financial conflicts of interest.

Adam Leitenberger is a medical journalist in the Philadelphia area who covers a wide range of specialties. Follow him on Twitter @adamleitenberg..

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