GLP-1s, SGLT-2s Slow Kidney Decline, But Only in Those With Albuminuria

The renal protection that made glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors central to kidney-focused diabetes care may not reach every patient who takes them. In a target trial emulation of 75,455 adults with type 2 diabetes published in The BMJ, the 2 drug classes cut the 5-year risk of renal deterioration by approximately 40% compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, but only among patients who already had albuminuria. Among the 61,583 patients without albuminuria, no renal benefit was apparent.^1,2

Benefit Tracked Closely With Albuminuria

Investigators linked electronic health records and claims data from 10 health systems and 2 national health insurance plans, following adults with type 2 diabetes at moderate cardiovascular risk who started a GLP-1 receptor agonist or SGLT-2 inhibitor, a sulfonylurea, or a DPP-4 inhibitor after metformin monotherapy between 2014 and 2022. The outcome was a doubling of serum creatinine or an estimated glomerular filtration rate (eGFR) below 15 mL/min/1.73 m², and median follow-up was 32 months.¹

Among patients with albuminuria (defined as an albumin to creatinine ratio of ≥30 mg/g), the estimated 5-year risk was 3.2% (95% CI, 2.3%-4.1%) with a GLP-1 receptor agonist or SGLT-2 inhibitor versus 5.4% (95% CI, 4.2%-6.7%) with a DPP-4 inhibitor, a risk ratio of 0.60 (95% CI, 0.42-0.82). Among patients without albuminuria, the corresponding risks were 2.4% (95% CI, 2.1%-2.7%) and 2.1% (95% CI, 1.8%-2.6%), a risk ratio of 1.10 (95% CI, 0.90-1.38).¹

Sulfonylureas Carried a Signal of Their Own

Among patients without albuminuria, sulfonylureas were associated with an estimated 5-year renal risk of 2.8% (95% CI, 2.5%-3.2%), a risk ratio of about 1.31 (95% CI, 1.11-1.58) versus DPP-4 inhibitors. The authors wrote that little is currently known about how sulfonylureas affect renal function and called for further research, noting that earlier observational work comparing sulfonylureas with metformin may have been confounded by differences between treatment groups.¹

That finding lands on ground pharmacists already occupy. Katelyn O'Brien, PharmD, BCPS, CDCES, BC-ADM, clinical pharmacy specialist in endocrinology at Boston Medical Center, described the deprescribing handoff as part of routine practice in an interview with Pharmacy Times at the New England Institute of Ambulatory Care Pharmacists 2026 Annual Forum. “If I’m starting this medication, we're going to be stopping the sulfonylurea to reduce risks of hypoglycemia and weight gain,” she said, adding that the change has to reach the dispensing pharmacy “so they don’t continue to fill it even though it's off the medication list in their profile.”³

Albuminuria Status Belongs in the Medication Review

Because benefit is tracked so closely with albuminuria, a urine albumin-to-creatinine ratio is worth confirming before a second-line agent is selected and worth flagging when it is missing. Roughly 82% of this cohort had no albuminuria at baseline, and the authors noted that preventing kidney function decline in that population remains unresolved. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have improved renal outcomes only in patients with severely increased albuminuria, and finerenone (Kerendia; Bayer) has not been tested in patients without it.¹

Speed of benefit is a separate argument for not letting initiation drift. “Reducing heart failure exacerbations, reducing cardiovascular events, delaying the progression of kidney disease—some of those things, those benefits can happen in mere months,” O’Brien said, pointing to prior authorization workflows and patient assistance programs as places where pharmacists and pharmacy technicians can compress the delay.³

Counseling Points Do Not Change

None of this alters the standing safety conversation at SGLT-2 inhibitor initiation. O’Brien said she counsels patients on genitourinary adverse effects and on euglycemic diabetic ketoacidosis (DKA) risk, including sick day management. “I always counsel patients around sick day management, holding medications when they're feeling sick or have something like [influenza] or COVID to prevent that DKA,” she said, noting that the drugs should also be held before planned procedures and that patients established on therapy for years often need the reminder as respiratory season begins.³

REFERENCES

1. Turchin A, Petito LC, Hegermiller E, et al. Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation. BMJ. 2026;394:e100574. doi:10.1136/bmj-2026-100574

2. GLP-1 and SGLT-2 diabetes drugs may help slow kidney damage. News release. BMJ Group. September 16, 2026. Accessed September 16, 2026. https://www.eurekalert.org/news-releases/1144049?

3. O’Brien K, Halpern L. Pharmacists as the glue in cardio-kidney-metabolic care. Pharmacy Times. September 11, 2026. Accessed September 16, 2026. https://www.pharmacytimes.com/view/pharmacists-as-the-glue-in-cardio-kidney-metabolic-care