Only Small Minority of Eligible Patients Prescribed SGLT2 Inhibitors

Uptake of sodium-glucose cotransporter 2 (SGLT2) inhibitors among US patients eligible for treatment according to clinical guidelines is extremely low, no matter their diabetes status, according to new real-world data.

“There is overwhelming evidence that SGLT2 inhibitors have cardiovascular and kidney protective effects in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” lead author Jung-Im Shin, MD, PhD (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD), told TCTMD in an email. “However, compared to the earlier time periods, we did not observe substantial improvement in guideline-recommended SGLT2-inhibitor prescription rates in patients with diabetes, and SGLT2-inhibitor prescription rates were similar regardless of presence or absence of a class 1a recommendation.

“We were struck,” Shin said, “by this lack of improvement and adherence to the guidelines in the diabetes population.”

Countless studies have shown the benefits of these drugs, most recently in patients with heart failure and functional mitral regurgitation, and both US and European guidelines give class 1a recommendations for SGLT2 inhibitors as first-line therapy among patients who have diabetes with either atherosclerotic cardiovascular disease, chronic kidney disease, or heart failure. Among those without diabetes, the medications have a class 1a recommendation in patients with a urine albumin-to-creatinine ratio ≥ 200 mg/g or heart failure.

Yet this isn’t the first study to show that SGLT2 inhibitors are not being prescribed as often as they are warranted.

Stephen J. Greene, MD (Duke Clinical Research Institute, Durham, NC), who was not involved in the study, told TCTMD he was “unfortunately” not surprised by the new findings.

“I think it's really just consistent with [the] overwhelming culture of clinical inertia for our care of cardio-kidney-metabolic patients, and we essentially sleepwalk through chronic care of these patients. And it leads, unfortunately, to a lot of preventable deaths and hospitalizations that could have been avoided if we had timely initiation of evidence-based therapy, like an SGLT2 inhibitor.”

Prescribing Patterns

For the study, published in the August 20, 2024, issue of the Journal of the American College of Cardiology, Shin and colleagues included data from Optum Labs on 3,189,827 adults treated at one of 28 US health systems between April 2022 and March 2023.

Of the 716,387 patients with diabetes, 63.4% had a class 1a recommendation for SGLT2 inhibitor therapy, but only 11.9% were treated with either canagliflozin (Invokana; Janssen), dapagliflozin (Farxiga; AstraZeneca), empagliflozin (Jardiance; Boehringer Ingelheim/Eli Lilly), or ertugliflozin (Steglatro; Merck Sharp & Dohme). The rate of ACE inhibitor or ARB use among these diabetic patients was 57.9%, but slightly higher, at 78.7%, for those who were also taking SGLT2 inhibitors.

Among the 2,473,440 adults without diabetes, 6.2% had a class 1a recommendation for SGLT2 inhibitor therapy and still only 3.1% of them received a prescription. ACE inhibitors or ARBs were prescribed in 46.6% of this population, but in 87.6% of those also taking SGLT2 inhibitors.

Prescriptions for SGLT2 inhibitors were most often written by internists and family practitioners for patients with diabetes and by specialists for those without the disease.

Across health systems, the median prescription rates of SGLT2 inhibitors were 12.0% for diabetes and 2.5% for no diabetes, and none surpassed a rate of 25% or higher for those with class 1a recommendations. However, health systems had higher prescription rates if they had more patients with commercial insurance and fewer with Medicare.

All of primary care doctors, endocrinologists, nephrologists, and cardiologists have an opportunity to see patients eligible for SGLT2 inhibitors. Jung-Im Shin

Shin said the reasons for low use of SGLT2 inhibitors in clinical practice are likely multifactorial. “Limited insurance coverage, high out-of-pocket costs, or formulary restrictions are certainly among the important barriers,” she said. “We hope the Inflation Reduction Act will alleviate financial constraints and encourage more optimal prescribing of SGLT2 inhibitors.”

She, too, blamed “clinical inertia” for the underuse of these drugs. “Efforts to educate both patients and providers about the updated guidelines for SGLT2 inhibitors, combined with improvements in access and affordability, could enhance adoption,” Shin said.

Because of the wide swath of indications for SGLT2 inhibitors, many types of prescribers can enhance their use, she argued. “All of primary care doctors, endocrinologists, nephrologists, and cardiologists have an opportunity to see patients eligible for SGLT2 inhibitors, and thus have shared responsibility to provide quality care,” Shin said. “I think we need patient-centered care with better coordination across different specialties to improve.”

‘Widespread, Systemic Underuse’

The problems identified by this study are important but not exclusive to SGLT2 inhibitors, according to Greene.

“We have widespread, systemic underuse of guideline-directed medical therapies, both branded and unbranded,” he said, adding that access and affordability are not the only culprits. “Novel drugs seem to be particularly impacted on this, and there's slow adoption of pretty much all novel therapies, unfortunately. But this example is another in a long list of examples that show that many patients are having poor outcomes and dying without ever [being] given an opportunity to benefit from a guideline-recommended therapy proven to help them.”

Greene agreed that increasing the prescription of SGLT2 inhibitors should be an “all-hands-on deck” situation. “Every encounter with an eligible patient is an opportunity, whether it's inpatient, outpatient, whether you're in cardiology clinic, whether you're in kidney clinic, or endocrinology clinic,” he said. “And particularly for our patients with heart failure, . . . delaying this therapy is just needless exposure to excess clinical risk.”

Particularly for our patients with heart failure . . . delaying this therapy is just needless exposure to excess clinical risk. Stephen J. Greene

Though some healthcare systems are doing a better job than others, Greene said this “analysis shows that really there's very few hospitals that are doing this well. Almost every hospital could stand to improve.” Similarly, he continued, “there’s no group [of patients] that's doing well with utilization of therapy. So we need all the help we can get to really address this across the board.”

To move forward, Greene would like to see a “sense of urgency instilled” in the heart failure and cardiovascular-kidney-metabolic communities, not unlike the oncology field has done even for therapies with harsh side effects.

“If you look at the therapies that we're talking about in cardio-kidney-metabolic conditions, we on average have much stronger efficacy data [and] much, much better tolerated therapies on the whole,” he said. “Our patients oftentimes face risks that are comparable to cancer, yet we have a culture of hesitancy.”

In an accompanying editorial, Tariq Ahmad, MD, MPH, Nihar R. Desai, MD, MPH, and Sara Tabtabai, MD (all Yale School of Medicine, New Haven, CT), write that the data have profound implications for clinical practice. “Although we are quick to advocate for the need for more robust evidence in cardiovascular care, here is a shining example in which those calls have been more than met,” they say, adding that the patterns also illustrate how painstaking and laborious formation of clinical guidelines do not always influence practice.

The editorialists argue that healthcare professionals “must accept our share of the responsibility for the suboptimal provision of quality care.” Additionally, they identify several specific barriers that must be overcome to improve SGLT2-inhibitor prescription: “the chaos of ambulatory care, the fear of offending a colleague by prescribing a medication that may have been their purview historically, and the need to navigate a fee-for-service system that incentivizes quantity over quality of care.”