Nearly 150 Million US Adults Eligible for CKM Syndrome Meds

Up to six in 10 US adults meet Food and Drug Administration-approved indications for medications aimed at treating cardiovascular-kidney-metabolic (CKM) syndrome, according to an analysis of observational data.

In all, approximately 148 million US adults would be eligible for at least one of the three novel CKM therapies: either a glucagon-like peptide-1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, or nonsteroidal mineralocorticoid receptor antagonist (MRA). An estimated 11.7 million people potentially qualify for triple therapy, researchers report online this week in JAMA Cardiology.

Louisa A. Mounsey, MD (Beth Israel Deaconess Medical Center, Boston, MA), the paper’s lead author, called the prevalence of CKM syndrome “staggering.” The American Heart Association recently pointed out in its 2026 heart disease and stroke statistics that the condition is present in as many as 90% of US adults.

Yet “what’s really exciting,” she told TCTMD, “is that we have novel therapies to address the consequences of CKM syndromes,” so it’s important to see how many individuals are actually eligible to receive these medications.

This information could be useful at a policy level, though it doesn’t speak to the clinician decision-making that occurs at an individual level, Mounsey added. “Whether a patient should receive these therapies does depend on full clinical context, but nonetheless, our findings do highlight the substantial size of the population that could potentially benefit under the current approval criteria.”

Whether a patient should receive these therapies does depend on full clinical context. Louisa A. Mounsey

Mounsey and colleagues combined data from the National Health and Nutrition Examination Survey (NHANES; n = 14,700, representing 245 million US adults) as well as five pooled community-based cohort studies (n = 30,929), including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular End-stage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study, plus two ambulatory healthcare samples from Beth Isreal Deaconess Medical Center (n = 94,714) and Mass General Brigham (n = 362,485).

Mean age ranged from 46 to 63 years across the cohorts and the percentage of female participants from 52% to 61%.

The proportions of people eligible for either an SGLT2 inhibitor, a GLP-1 drug, or a nonsteroidal MRA ranged from 42% in the Beth Israel Deaconess cohort up to 61% in the community-based cohort studies. Overall, eligibility for GLP-1 medications was the most common (46%-56%), followed by SGLT2 inhibitors (14%-33%) and nonsteroidal MRAs (1%-5%). Around 12%-17% were eligible for both a GLP-1 receptor agonist and an SGLT2 inhibitor, while 1%-5% were potential candidates for all three drug classes.

Based on the NHANES database, in particular, approximately 137 million individuals were eligible for a GLP-1 drug, 57 million for an SGLT2 inhibitor, and 11 million for a nonsteroidal MRA.

“Despite increasing real-world use of CKM therapies, our findings highlight a substantial potential treatment gap that remains,” the authors write. As of 2023, for example, fewer than 1 million people in the US were prescribed GLP-1 receptor agonists.

To assess the potential impact of underuse, investigators also looked at age- and sex-adjusted outcomes.

Among individuals in the pooled cohorts who were eligible for a GLP-1 medication, the MI rate ranged from 5.4 per 1,000 person-years for those with a body mass index of at least 30 kg/m² up to 9.3 per 1,000 person-years for those with type 2 diabetes and CVD. In the ambulatory cohorts, these rates were 22.9 and 22.2 per 1,000 person-years, respectively. All-cause mortality rates per 1,000 person-years for those with type 2 diabetes and CVD reached 29.4 in the pooled cohorts, 32.6 in the Beth Israel Deaconess data, and 39.3 in the Mass General Brigham data.

Among those eligible for an SGLT2 inhibitor, all-cause mortality rates for patients with heart failure were 34.1, 50.2, and 71.4 per 1,000 person-years in the pooled, Beth Israel Deaconess, and Mass General Brigham cohorts, respectively. Most of those events occurred in patients not on CKM medications.

“Our findings highlight the urgency and widespread relevance of addressing barriers to implementation,” the study authors write. This is especially true given that SELECT, LEADER, CANVAS, and other “event-driven randomized clinical trials have shown that they can mitigate substantial CV risk associated with the progression of CKM syndrome.”

Barriers exist across multiple levels, Mounsey stressed. These include “cost, insurance, medication access and shortages, administrative burden on the providers and the healthcare system, and then on the patient level, [difficulties with] long-term adherence due to side effects, among other challenges,” she noted, adding that while their paper helps to define the potential scope of the issue, there remains the question of how to put this knowledge into practice. That will likely require coordinated efforts at a policy level.