Effectiveness of Adding GLP-1 Receptor Agonists to SGLT2 Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study
In brief
Adding GLP-1 drugs to SGLT2 therapy linked to 30% fewer kidney events
In a matched real-world study of 32,448 adults with chronic kidney disease, those who added a GLP-1 receptor agonist had 30% fewer major kidney events over a median 12 months than those taking an SGLT2 inhibitor alone. They also had fewer cardiovascular events and deaths, but more gastrointestinal symptoms, genital infections and worsening retinopathy; randomized trials are needed to confirm the benefits.
- Journal
- Diabetes, obesity & metabolism (Q1)
- Published
- 27 September 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Hussain Salim, Shaheer Qureshi, Gaurav S Gulsin, Habib R Khan, Saad Ahmed Waqas, Gerry P McCann, et al.
- PMID
- 42802242
- DOI
- 10.1111/dom.71375
Why clinicians should know about it
- Picked for Nephrology (paper of the day, 2 October 2026): Real-world CKD cohort, combined GLP-1RA/SGLT2i outcomes
Abstract
BACKGROUND: Individually, sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce major kidney and cardiovascular events in patients with chronic kidney disease (CKD). However, evidence supporting combined GLP-1RA and SGLT2i therapy in this population remains limited. METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adults with CKD treated with SGLT2i alone or SGLT2i with subsequent initiation of GLP-1RA between June 2020 and December 2023. Propensity score matching (1:1) adjusted for demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse kidney events (MAKE); secondary outcomes included all-cause mortality and major adverse cardiovascular events (MACE). Time-to-event analyses were performed using Cox proportional hazards models. RESULTS: Among 112 596 patients with CKD, 16460 received SGLT2i and GLP-1RA combination therapy, and 96 136 received SGLT2i monotherapy. The matched cohort included 32 448 patients (16 224 per group). Over a median follow-up of 12 months, the addition of a GLP-1RA was associated with lower rates of the primary outcome of MAKE (HR 0.70; 95% CI 0.65-0.74; p < 0.001) compared with SGLT2i monotherapy. Combination therapy was also associated with lower risks of MACE (HR 0.83; 95% CI 0.78-0.87) and all-cause mortality (HR 0.55; 95% CI 0.50-0.61). Benefits were consistent across CKD stages and diabetes status, with significantly more pronounced effects observed in patients with obesity, heart failure, and ischemic heart disease. Combination therapy was associated with increased gastrointestinal symptoms, genital infections, and retinopathy progression, but lower risks of volume-depletion events and acute kidney injury. CONCLUSIONS: In this real-world CKD cohort, GLP-1RA added to SGLT2i therapy was associated with substantial incremental reductions in kidney disease progression and cardiovascular events. These findings suggest an additive cardiorenal benefit, particularly in patients with obesity, supporting the evaluation of combination therapy in future randomised trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.