Type 2 diabetes increases the risk of chronic kidney disease, which makes preventing kidney failure a key part of treatment. Newer diabetes medications, including GLP-1s and SGLT2 inhibitors, can reduce the risk of kidney disease, but previous studies have included large proportions of patients who already had signs of kidney damage, making it unclear whether the findings applied to patients without kidney damage.
A new study led by Mass General Brigham researchers has found that GLP1 agonists and SGLT2 inhibitors reduced the risk of kidney deterioration in patients with diabetes who had protein in their urine, a sign of kidney damage, prior to treatment, but the researchers found little evidence of kidney benefit among patients without protein in their urine. They also showed that sulfonylureas, an older class of diabetes medication, led to faster declines in kidney function in patients with diabetes who didn't have protein in their urine. Results are published in the BMJ .
"Our study shows that we need to tailor diabetes treatment to the individual patient instead of using a one-size-fits-all approach," said corresponding author Alexander Turchin, MD, MS , of the Division of Endocrinology in the Mass General Brigham Department of Medicine. "A simple urine test could help doctors assess whether a patient may receive kidney protection from GLP-1 receptor agonists or SGLT-2 inhibitors and whether sulfonylureas could pose additional risk."
The researchers analyzed medical record data from 75,455 patients with type 2 diabetes from across the U.S., including 13,872 who presented with protein in their urine. They followed the patients for up to five years and compared the risk of developing chronic kidney disease for patients prescribed GLP-1s and SGLT2 inhibitors versus patients prescribed sulfonylureas or DPP4i. All the patients had moderate cardiovascular risk and were receiving treatment with metformin as their primary diabetes medication.
Among patients with protein in their urine, GLP-1s and SGLT2 inhibitors were associated with substantially better kidney outcomes compared to DPP4i, but GLP-1s/SGLT2is did not appear to provide a significant kidney benefit in patients without protein in their urine. Among patients without protein in their urine at baseline, treatment with sulfonylureas was associated with an increased risk of kidney deterioration compared to DPP4i.
Further research is needed to identify therapies to prevent kidney disease in the large population of type 2 diabetes patients who don't present with protein in their urine, the researchers say.
"These findings will allow us to individualize medication choices that maximally benefit the patient in front of us rather than for the hypothetical 'average person,'" said Turchin. "Patients and their doctors should discuss how to balance these different risks and benefits in their individual circumstances when choosing their type 2 diabetes medications."
Authorship: In addition to Turchin, Mass General Brigham authors include Marie E. McDonnell. Additional authors include Lucia C. Petito, Emma Hegermiller, Indhumathy Chelliah, Ryan M. Carnahan, Andrea DeVries, Satyender Goel, M. Cecilia Lansang, Vinit Nair, Elisa Priest, Vincent J. Willey, Alan F. Kaul, and Miguel A. Hernán.
Disclosures: Turchin reports grants from Eli Lilly and personal fees from Novo Nordisk and Proteomics International. Additional author disclosures can be found in the paper.
Funding: This research was funded in part by the Patient-Centered Outcomes Research Institute (contracts DB-2020C2-20308 and RI-MISSOURI-01-PS1). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
Paper cited: Turchin, A. 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. DOI: 10.1136/bmj-2026-100574
