JAMA Cardiol. 2026 Jan 28. doi: 10.1001/jamacardio.2025.5305. Online ahead of print.
ABSTRACT
IMPORTANCE: The prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.
OBJECTIVE: To examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.
DESIGN, SETTING, AND PARTICIPANTS: This study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.
EXPOSURES: FDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.
MAIN OUTCOMES AND MEASURES: Medication class eligibility within each study sample.
RESULTS: The proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).
CONCLUSIONS AND RELEVANCE: This study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.
PMID:41604173 | DOI:10.1001/jamacardio.2025.5305