SGLT2 Inhibitors in T2D Lower 5-Year Risk of CKD and Acute Kidney Injury

Results from a comparative effectiveness study conducted in Denmark show that initiation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment in patients with type 2 diabetes (T2D) was associated with a lower 5-year risk of chronic kidney disease (CKD) and a lower 5-year count of acute kidney injury (AKI). The research, published in JAMA Internal Medicine, demonstrates the potential of SGLT2is to be the primary prevention treatment of choice to reduce the risk of kidney disease.¹

SGLT2s Versus GLP-1s: A Comparative Analysis of Efficacy in CKD

The investigators compared SGLT2is to glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the class of drugs that has spurred revolutionary treatments for weight loss like semaglutide (Wegovy, Ozempic; Novo Nordisk) and tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company). Each class of drugs remains pivotal in current T2D guidelines, but until this current analysis, their comparative effectiveness for reducing acute and CKD was uncertain.¹

Following comparisons, investigators found a 6.7% 5-year risk of CKD (95% CI, 6.4% to 7.0%) for treatment with SGLT2is, while it was 8.2% (95% CI, 7.8% to 8.6%) for patients initiating GLP-1 RAs (risk ratio [RR], 0.81; 95% CI, 0.76 to 0.87; risk difference [RD], –1.5%). Furthermore, the 5-year mean cumulative count (MCC) of AKI per 100 individuals was 25.2 (95% CI, 24.4 to 26.1) for SGLT2i initiators and 28.7 (95% CI, 27.4 to 30.0) for GLP-1 RA initiators, with an MCC ratio of 0.88 (95% CI, 0.83 to 0.93) and an MCC difference of –3.5%.¹

Individual components of CKD were assessed. Initiating SGLT2i treatment was associated with a lower risk of sustained reduction in estimated glomerular filtration rate (eGFR) (RR, 0.75; 95% CI, 0.69 to 0.82; RD, –1.4%) and kidney failure (RR, 0.77; 95% CI, 0.54 to 1.11; RD, –0.1%) compared with GLP-1 RAs. The risk of severe albuminuria, which is the presence of blood protein in the urine, was similar in the 2 treatment groups, according to the investigators.¹

Five-year risks of incident or progressive albuminuria were 16.1% for SGLT2i initiators and 15.0% for GLP-1 RA initiators, corresponding to an RR of 1.07 (95% CI, 1.02 to 1.12) and an RD of 1.1% (95% CI, 0.4% to 1.8%). Interestingly, despite the improvements in key indicators of CKD and kidney injury, 5-year mortality was slightly higher for SGLT2i initiators (9.7%) compared with GLP-1 RA initiators (9.3%).¹

What Should Pharmacists Consider When Prescribing?

Authors noted that the on-treatment analyses reflected the intention-to-treat analyses, with marginally larger relative differences across both primary and secondary outcomes. Therefore, the authors ultimately determined that SGLT2i initiation was associated with a lower risk of CKD and count of AKI, as well as lower risks of sustained reduction in eGFR and kidney failure when compared with GLP-1 RA initiation.¹

Since the proliferation of GLP-1 RAs and SGLT2is, patients have had a litany of novel options to reduce their cardiometabolic risk. However, the choice to use either treatment should be based on individual patient factors, with a pharmacist able to play a key role in counseling patients on which option may be best for their current situation. Many pharmacists, including Heather Johnson, PharmD, BCACP, CTTS, an assistant professor of clinical pharmacy at West Virginia University School of Pharmacy, may prefer SGLT2is, especially in CKD or heart failure.^1,2

SGLT2is have demonstrated nephroprotective effects in individuals with a normal or impaired GFR, with effects also observed in non-diabetic, normotensive individuals. This suggests that the mechanisms of SGLT2is extend beyond glucose lowering and weight loss. SGLT2is induce more sodium to pass along the nephron, which protects glomeruli and reduces intraglomerular pressure. They also improve tubular oxygenation and metabolism while reducing fibrosis and renal inflammation. Overall, they have a significant protective effect against the development of CKD and should be recommended for patients based on their present medical condition and other considerations like dosing and availability.³

“Anything to preserve that eGFR is going to have a significant impact on cardiovascular health,” Johnson explained during a session at the 2025 American Pharmacists Association Annual Meeting and Exposition. “SGLT2s are also known to be protective against AKI, while GLP-1s can cause AKIs.”²

REFERENCES

1. Jensen SK, Heide-Jørgensen U, Andersen IT, et al. SGLT2 inhibitors vs GLP-1 receptor agonists for kidney outcomes in individuals with type 2 diabetes. JAMA Intern Med. Published Online January 20, 2026. doi:10.1001/jamainternmed.2025.7409

2. Hippensteele A. APhA 2025: GLP-1 receptor agonists vs SGLT2 inhibitors show varied benefit for cardiovascular outcomes in patients with diabetes. Pharmacy Times. Published March 23, 2025. Accessed February 6, 2026. https://www.pharmacytimes.com/view/apha-2025-glp-1-receptor-agonists-vs-sglt2-inhibitors-show-varied-benefit-for-cardiovascular-outcomes-in-patients-with-diabetes

3. Bailey CJ, Day C, Bellary S. Renal protection with SGLT2 inhibitors: Effects in acute and chronic kidney disease. Curr Diab Rep. 2022;22(1):39-52. doi:10.1007/s11892-021-01442-z