SGLT2 Inhibitors Benefit Frail Adults With T2D, Remain Underused

Overall, approximately 55.1% of patients received neither drug class, 18.3% received a GLP-1 RA alone, 13.8% received an SGLT2 inhibitor alone, and 12.8% received both. Among those with an estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m2, adjusted hazard ratios (HRs) for all-cause death were about 0.33 (95% CI, 0.32-0.34) with an SGLT2 inhibitor alone, 0.46 (95% CI, 0.44-0.48) with a GLP-1 RA alone, and 0.26 (95% CI, 0.25-0.28) with both. In patients with an eGFR below 30 mL/min/1.73 m2, the corresponding HRs were 0.24 (95% CI, 0.19-0.29), 0.55 (95% CI, 0.48-0.61), and 0.17 (95% CI, 0.13-0.23).2

Caution vs Undertreatment

Older age, female sex, lower eGFR, and cerebrovascular disease were associated with receiving neither agent.2 In an interview with Pharmacy Times, Kalantar-Zadeh said the gap is not simply clinical inertia.

“I believe this reflects a combination of legitimate clinical concerns and appropriate risk aversion,” he explained. “In older adults, polypharmacy can cause harm, including volume depletion, gastrointestinal adverse effects, and acute kidney injury.”

Patients with eGFR below 25 mL/min/1.73 m2 “have limited renal reserve and are especially vulnerable to poorly considered prescribing decisions,” according to Kalantar-Zadeh. “The challenge is distinguishing appropriate caution from avoidable undertreatment.”

Current guidance favors treatment. The American Diabetes Association 2026 Standards of Care recommend an SGLT2 inhibitor or a GLP-1 RA for patients with T2D and CKD (level A evidence), and they prefer a GLP-1 RA in advanced CKD (level B evidence). The standards also position both classes as core risk-reduction strategies regardless of hemoglobin A1C.3,4

Where Pharmacists Fit

Kalantar-Zadeh sees pharmacists as central to closing the gap. “We need embedded pharmacists in every CKD clinic,” he said. “As integral members of the clinical team, pharmacists can optimize medications, educate patients, monitor adverse effects, reinforce sick-day precautions, and help navigate insurance coverage and affordability.”

He also pointed to dosing practice. “I also value pharmacists’ attention to creatinine clearance and drug-specific dosing recommendations, rather than relying exclusively on body surface area–indexed eGFR,” he said. “This distinction is particularly important in patients with advanced CKD, where individualized medication decisions and preservation of residual kidney function are paramount.”

REFERENCES1. Moon SJ, Lee JH, Park JT. Kidney and cardiovascular outcomes of SGLT2 inhibitors as add-on therapy to metformin in frail patients with type 2 diabetes. Abstract SA-PO0405. Presented at: ASN Kidney Week 2026; October 24, 2026.2. Cohen-Hagai K, Zitman-Gal T, Kalantar-Zadeh K, et al. Bridging the treatment gap: SGLT2 inhibitors and GLP-1 receptor agonists and outcomes in patients with diabetes and CKD. Abstract SA-PO0406. Presented at: ASN Kidney Week 2026; October 24, 2026.3. Type 2 diabetes guideline side-by-side: ADA Standards of Care 2026 vs AACE 2026 algorithm. Guideline Central. September 3, 2026. Accessed October 16, 2026. https://www.guidelinecentral.com/insights/sep-2026-type2diabetes-guideline-sidebyside/4. Dixon D, Halpern L. ADA 2026: The 2026 ADA Standards—a pharmacist’s guide to cardiorenal risk reduction. Pharmacy Times. June 5, 2026. Accessed October 16, 2026. https://www.pharmacytimes.com/view/ada-2026-the-2026-ada-standards-a-pharmacist-s-guide-to-cardiorenal-risk-reduction