SGLT2is Significantly Benefit Kidney, Hospitalization, and Mortality Outcomes

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) exhibited significantly clear and absolute benefits on outcomes pertaining to the kidneys, hospitalization, and mortality regardless of patients’ diabetes status or urine albumin to creatinine ratio (UACR).

“There are an estimated 850 million people with chronic kidney disease (CKD) globally; CKD is associated with substantially increased risks of kidney failure and cardiovascular disease (CVD),” wrote authors of a study published in JAMA.¹ “SGLT2is reduce the risk of kidney failure and CVD in individuals with CKD or heart failure, and the use of SGLT2is is recommended as a standard of care for adults with these conditions.”

Originally developed as diabetes medications because of their glucose-lowering abilities,² SGLT2is are now being utilized to improve heart and kidney health, becoming a staple for people experiencing CKD and cardiovascular complications.³

READ MORE: SGLT2is Lower CKD Risk Regardless of eGFR, Albuminuria

Multiple uncertainties, however, regarding SGLT2i effects continue to limit the use of these drugs among people with various subtypes of CKD. These uncertainties are specific to patients exhibiting an estimated glomerular filtration rate (eGFR) of 20 to 45 mL/min/1.73 m² and a UACR of less than 200 mg/g.¹

However, as data from the current study is released, experts are uncovering brand-new insights on SGLT2i medications from the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C). Previous data from the consortium explored the efficacy of SGLT2is and found significant benefits regardless of patients’ eGFR and albuminuria.⁴

The current study is now exploring both the relative and absolute effects of SGLT2is when clinical trials stratified for UACR as well as diabetes status.

“In this collaborative meta-analysis, we first aimed to quantify post-hoc the relative effects of SGLT2 inhibition across the full range of clinical efficacy and relevant serious safety outcomes reported within relevant, large, placebo-controlled, randomized clinical trials (RCTs),” they continued.¹ “Second, we assessed the net absolute effects within the included trial populations. Third, we focused on subgroups with different strengths of evidence in current CKD guidelines (ie, by UACR ≥200 mg/g vs <200 mg/g after stratifying by diabetes status) rather than on CKD staging categories.”

Through SMART-C, representatives from various RCTs exploring SGLT2i effects gathered to present data on patients’ safety and efficacy outcomes. In the current exploration of SMART-C data, trial researchers aimed to assess RCTs that specifically stratified for UACR and diabetes. The meta-analysis included a total of 8 RCTs and the researchers’ primary objective was the estimation of effects for SGLT2is on patients with CVD, CKD, type 2 diabetes (T2D), and other clinical characteristics.

The final meta-analysis included a total of 58,816 patients (mean age, 64 years; 35% women; 83% had diabetes). The 8 RCTs included featured studies comparing SGLT2is with placebo.

After data collection, researchers found that SGLT2is reduced the rate of CKD progression, acute kidney injury, hospitalization, and all-cause mortality.¹

“The overarching objective was to explore the effects of diabetes status and albuminuria on the net absolute effects of SGLT2 inhibition on the clinical efficacy and relevant serious safety outcomes reported within large, placebo-controlled RCTs,” the authors wrote. “The relative benefits for kidney disease progression, acute kidney injury, hospitalization for any cause, and cardiovascular death were generally similar in the analyses stratified by diabetes status and then by baseline UACR category.”

Further highlighting the expanding benefits of SGLT2is, data from the analysis adds to this drug class and its capabilities among patients with various disease states, particularly CKD. First, with their efficacy in patients regardless of eGFR and albuminuria, SGLT2is are now being accepted by experts as beneficial to patients regardless of their diabetes diagnoses or levels of UACR.

Amid this continuously expanding scope of use for this medication class, experts are currently prioritizing the access of SGLT2is to promote kidney health among patients in need.

“Within the studied participants, there were clear absolute benefits of SGLT2is on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR,” they concluded.¹ “Availability of generic SGLT2is now, and in the near future, will help facilitate more equitable use globally, improve cost-effectiveness further, and help achieve the objectives of a 2025 World Health Organization resolution. This resolution has recognized that the burden of noncommunicable diseases globally can be reduced through the promotion of kidney health and by strengthening the prevention and control of kidney disease.”

READ MORE: Diabetes Resource Center

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REFERENCES

1. Staplin N, Roddick AJ, Neuen BL, et al. Effects of sodium glucose cotransporter 2 inhibitors by diabetes status and level of albuminuria: a meta-analysis. JAMA. November 07, 2025. doi:10.1001/jama.2025.20835

2. Nowosielski B. SGLT2is lower CKD risk regardless of eGFR, albuminuria. Drug Topics. November 11, 2025. Accessed November 11, 2025. https://www.drugtopics.com/view/sglt2is-lower-ckd-risk-regardless-of-egfr-albuminuria

3. SGLT2 inhibitors. Cleveland Clinic. July 31, 2025. Accessed November 11, 2025. https://my.clevelandclinic.org/health/treatments/sglt2-inhibitors

4. Neuen BL, Fletcher RA, Anker SD, et al. SGLT2 inhibitors and kidney outcomes by glomerular filtration rate and albuminuria: a meta-analysis. JAMA. November 07, 2025. doi:10.1001/jama.2025.20834