Despite a large number of patients with T2D being eligible for guideline-recommended, cardioprotective, anti-hyperglycemic therapies, substantial gaps exist in the use of SGLT-2 inhibitors and GLP-1RAs, according to a study. Efforts are needed to increase uptake of these therapies.


Optimizing the management of cardiovascular complications continues to be an important need in the care of patients with T2D. The therapeutic landscape for T2D has changed dramatically with the emergence of sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs). “These therapies represent the only drug classes with evidence for reducing the risk for adverse cardiovascular events in patients with T2D in large randomized clinical trials,” says Rohan Khera, MD, MS. “The important role of these therapies is increasingly being recognized in national guidelines.”

The expanding indications for using SGLT-2 inhibitors and GLP-1RAs build upon the significant reductions in major adverse cardiovascular events in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD). “While we’ve made great strides in developing novel drugs to reduce cardiovascular complications, there is little data on how frequently SGLT-2 inhibitors and GLP-1RAs are being given to patients with T2D who qualify for these treatments,” Dr. Khera says. “It’s critical that we use these cardioprotective agents in patients with compelling indications.”

Significant Underutilization

For a study published in the Journal of the American Heart Association, Dr. Khera and colleagues evaluated the proportion of patients with T2D who have compelling indications for SGLT-2 inhibitors, GLP-1RAs, or both, as well as the patterns of current use among those with and without indications, using nationally representative data. The researchers defined compelling indications for SGLT-2 inhibitors by the presence of cardiovascular disease or ASCVD, HF, or CKD. For GLP-1RAs, compelling indications were defined by the presence of established, or high risk for, ASCVD. The authors then evaluated utilization of these medications among patients with physician-diagnosed T2D.

The study team analyzed data on what represents approximately 10.6% of the United States population, or 33.2 million adults nationwide. “Our results showed that more than one half of patients were eligible for treatment with SGLT-2 inhibitors,” says Dr. Khera. “In addition, about one-third of patients had an indication for GLP-1RAs and one-quarter had an indication for both medications. Despite this eligibility, only 4.5% of patients were actually treated with SGLT-2 inhibitors and just 1.5% with GLP-1RAs.” The degree of underutilization for SGLT-2 inhibitors was highest among patients with CKD or albuminuria, followed by those with ASCVD and HF (Table).

In addition to the substantial gaps in utilization of these therapies overall, Dr. Khera says there appears to be inconsistent use among people who are most likely to benefit from SGLT-2 inhibitors and GLP-1RAs, including low rates of use among those with cardiovascular or renal disease. “Our findings suggest that these gaps can limit the potential of these therapies to provide important public health benefits,” Dr. Khera says.

Ensuring Treatment Receipt Among Eligible Patients

The study team noted several potential barriers to expanding the use of SGLT-2 inhibitors and GLP-1RAs to patients with compelling indications for them. “There’s no simple ‘one stop’ solution, but an important step is to keep affordability and other potential obstacles in mind when prescribing treatment to patients,” says Dr. Khera. “When possible, medical practices should aim to ensure that generic SGLT-2 inhibitors and GLP-1RAs are available on formulary. In addition, the slower adoption of these agents may suggest clinical inertia toward using novel agents or a lack of staying up to date with clinical guidelines.” He adds that the possible role of each of these factors warrants greater attention in future research.

“Our data should serve as a call to action to diabetes care teams, endocrinologists, and cardiologists,” Dr. Khera says. “We need to be vigilant about ensuring that patients who are eligible for treatment with SGLT-2 inhibitors and GLP-1RAs receive these important therapies. This requires honest discussions with patients about the potential benefits of these drugs. Furthermore, we need additional research to optimize the selection of patients who stand to benefit most from these agents.”