ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO0405

Kidney and Cardiovascular Outcomes of SGLT2 Inhibitors as Add-On Therapy to Metformin in Frail Patients with Type 2 Diabetes

Session Information

Category: Cardiovascular-Kidney-Metabolic Health

  • 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

  • Moon, Sung Jin, Catholic Kwandong University International Saint Mary's Hospital, Incheon, Korea (the Republic of)
  • Lee, Jin Hyeog, Catholic Kwandong University International Saint Mary's Hospital, Incheon, Korea (the Republic of)
  • Park, Jung Tak, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University,, Seoul, Korea (the Republic of)
Background

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) offer cardiorenal protection in type 2 diabetes (T2D) but raise concerns regarding adverse events like dehydration and muscle mass loss, particularly in frail elderly patients. Since randomized trials often exclude individuals with severe frailty, real-world evidence is essential to validate safety and efficacy in this vulnerable subgroup. This study compared long-term kidney and cardiovascular outcomes of SGLT-2is versus other second-line glucose-lowering drugs (oGLDs) in elderly T2D patients, stratified by frailty status.

Methods

We utilized the Korean National Health Insurance Service-Senior cohort to conduct a retrospective study applying a target trial emulation framework to minimize biases. Eligible participants were aged ≥60 years, on first-line metformin, and initiated SGLT-2is or oGLDs. Frailty was assessed using five validated claims-based indices. Propensity score matching was performed to adjust for confounders, and both intention-to-treat and per-protocol analyses were conducted. The primary outcome was a composite of kidney events; the secondary outcome was major adverse cardiovascular events (MACE).

Results

The study included 151,134 patients, with 14.0% classified as frail. Among frail individuals, SGLT-2i use was associated with a significant 30% risk reduction in composite kidney outcomes and a 19% reduction in MACE compared to oGLDs. Comparable benefits were observed in non-frail patients. While findings were generally robust, the kidney benefit in frail patients lost statistical significance when frailty was defined specifically by the electronic or global frailty scores, indicating potential heterogeneity.

Conclusion

SGLT-2i therapy demonstrated consistent cardiovascular and kidney benefits in elderly T2D patients regardless of frailty status, supporting its utility as a second-line option. However, the potential attenuation of kidney benefits observed with certain frailty definitions warrants careful patient monitoring and individualized treatment planning in this high-risk population.