Implications of the 2026 Cardiovascular-Kidney-Metabolic Syndrome Guideline for GLP-1 Receptor Agonist and SGLT2 Inhibitor Eligibility Among US Adults

Background

The 2026 cardiovascular-kidney-metabolic (CKM) syndrome guideline broadens recommendations for glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), but the increment over pre-2026 standards is unknown. We estimated the number and clinical profile of US adults newly eligible under this guideline.

Methods

Cross-sectional analysis of adults aged 30-79 years in the 2011-2018 National Health and Nutrition Examination Survey. Adults were newly eligible if they met 2026 CKM guideline indications but not pre-2026 American Diabetes Association, American College of Cardiology/American Heart Association heart failure, Kidney Disease: Improving Global Outcomes, or obesity guideline indications. Sensitivity analyses used 2 US Food and Drug Administration (FDA) label standards.

Results

Among 175.17 million US adults, 111.84 million (63.8%) were already eligible for either class. The CKM guideline added 7.48 million (95% CI: 6.48 to 8.47), a 6.7% increase, all for GLP-1RA and none for SGLT2i: 6.49 million with overweight (body mass index 27.0-29.9 kg/m2, ethnicity adjusted) and no other cardiometabolic disease, and 0.99 million with type 2 diabetes and 10-year PREVENT cardiovascular risk ≥7.5%. Newly eligible adults (86.8% CKM stage 1) were younger (46.2 vs 52.9 years), leaner (27.8 vs 33.0 kg/m2), and at lower 10- and 30-year PREVENT risk (3.6% vs 8.1%; 11.3% vs 19.6%; all P < 0.001). Against FDA labeling, 14.15-25.17 million were newly eligible (7.66-18.20 million for SGLT2i). Assuming a 20% relative risk reduction, the projected number needed to treat per cardiovascular event prevented was 243 over 10 years and 56 over 30 years (ages 30-59) in adults with overweight, versus 61 and 26 in already eligible adults.

Conclusions

Relative to pre-2026 society guidelines, the 2026 CKM guideline newly confers a GLP-1RA indication on 7.48 million US adults, predominantly at lower cardiovascular risk. Whether treating these adults improves outcomes in a cost-efficient manner remains to be established.

What Is Known

• The 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic (CKM) syndrome guideline recommends GLP-1 receptor agonists and SGLT2 inhibitors according to CKM stage, comorbidity, and PREVENT-predicted risk, including a GLP-1 receptor agonist for adults with overweight at CKM stage 1.

• National estimates of eligibility for these agents predate the guideline and have largely used FDA labeling, rather than professional society guidance, as the reference standard.

What the Study Adds

• Relative to pre-2026 society guidance, the guideline newly identifies 7.48 million US adults aged 30 to 79 years as treatment candidates, all for a GLP-1 receptor agonist and none for an SGLT2 inhibitor; most have overweight without other cardiometabolic disease.

• Newly eligible adults are younger and at lower predicted cardiovascular risk than those already eligible; the projected number needed to treat is 243 over 10 years and 56 over 30 years, so expected benefit rests on a lifetime horizon that outcome trials and cost-effectiveness analyses have not yet tested.