By: Michelle Flores, Pharm D Candidate 2027
A large comparative effectiveness study from Denmark has found that sodium-glucose cotransporter-2 inhibitors (SGLT-2is) may offer stronger kidney protection than glucagon-like peptide-1 receptor agonists (GLP-1s) in patients with type 2 diabetes (T2D). Researchers evaluated adults with metformin-treated T2D who began therapy with either an SGLT-2 inhibitor or a GLP-1receptor agonist (GLP-1 RA) between January 2014 and November 2020, with follow-up extending through October 2024. The analysis included 36,279 patients who initiated an SGLT-2 inhibitor and 18,782 who started a GLP-1 RA. The two groups were similar in age, duration of diabetes, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio at baseline.
Over five years, patients treated with SGLT-2 inhibitors had a 6.7% risk of developing chronic kidney disease (CKD), compared with 8.2% among those receiving GLP-1 RA. This translated to a 19% relative risk reduction and an absolute risk difference of 1.5% favoring SGLT-2 inhibitors. Rates of acute kidney injury (AKI) were also lower in the SGLT-2 group, with 25.2 events per 100 individuals over five years versus 28.7 per 100 in the GLP-1 group. When investigators examined individual components of kidney outcomes, SGLT-2 inhibitor use was associated with a lower risk of sustained eGFR decline and kidney failure compared with GLP-1 therapy. However, the risk of severe albuminuria was similar between groups. Five-year rates of incident or progressive albuminuria were slightly higher among SGLT-2 inhibitor users (16.1%) than GLP-1 users (15.0%), though the difference was modest.
Interestingly, despite improvements in several kidney-related endpoints, five-year mortality was slightly higher in the SGLT-2 inhibitor group (9.7%) compared with the GLP-1RA group (9.3%). Both SGLT-2 inhibitors and GLP-1RAs remain central to current T2D management guidelines. GLP-1RAs have gained widespread attention for their role in weight management and cardiometabolic risk reduction, while SGLT-2 inhibitors continue to demonstrate robust renal and cardiovascular benefits.
The nephroprotective effects of SGLT-2 inhibitors appear to extend beyond glucose lowering. By promoting sodium delivery to the distal nephron, these agents reduce intraglomerular pressure and help preserve kidney function. They also improve tubular oxygenation and metabolism while decreasing fibrosis and renal inflammation. Notably, kidney benefits have been observed even in patients without diabetes or hypertension, suggesting broader renal mechanisms at play.
Despite the lead of SGLT-2 inhibitors in renal preservation, medical guidelines continue to emphasize the importance of both drug classes in modern diabetes care. While SGLT-2 inhibitors are increasingly favored for direct kidney protection and heart failure management, GLP-1RAs remain the preferred choice for significant weight loss and reducing the risk of major adverse cardiovascular events like stroke and heart attack. Ultimately, the study reinforces that selecting between these therapies should be highly individualized, with pharmacists and physicians working together to weigh factors such as baseline kidney function, cardiovascular risk, and patient tolerability to ensure the best possible long-term outcomes.
REFERENCES:
- Steinzor P. SGLT2 inhibitors linked to lower risk of CKD, aki than GLP-1 Ras. January 21, 2026. Accessed February 21, 2026. https://www.ajmc.com/view/sglt2-inhibitors-linked-to-lower-risk-of-ckd-aki-than-glp-1-ras.
- Jensen SK, Jorgensen U-H, Anderson IT, Bonnesen K. SGLT2 inhibitors vs GLP-1 receptor agonists for kidney outcomes in individuals with type 2 diabetes. JAMA internal medicine. January 20, 2026. Accessed February 20, 2026. https://pubmed.ncbi.nlm.nih.gov/41557360/.
- Halpern L. SGLT2 inhibitors in T2D lower 5-year risk of CKD and Acute Kidney Injury | Pharmacy Times. February 6, 2026. Accessed February 21, 2026. https://www.pharmacytimes.com/view/sglt2-inhibitors-in-t2d-lower-5-year-risk-of-ckd-and-acute-kidney-injury.
