Effectiveness of Adding GLP‐1 Receptor Agonists to SGLT2 Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study
8 affiliations
- 1Department of Medicine Dow University of Health Sciences Karachi Pakistan
- 2National Institute of Health and Care Research, Leicester Biomedical Research Centre Glenfield Hospital Leicester UK
- 3Department of Cardiovascular Sciences, British Heart Foundation Cardiovascular Research Centre University of Leicester Leicester UK
- 4Division of Cardiology, Department of Medicine, Schulich School of Medicine and Dentistry Western University London Ontario Canada
- 5Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry Western University London Ontario Canada
- 6Cardiology Department Health Sciences North, Northern Ontario School of Medicine University Sudbury Ontario Canada
- 7Diabetes Research Centre University of Leicester Leicester UK
- 8Keele Cardiovascular Research Group, Centre for Prognosis Research, School of Medicine Keele University Keele UK
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.
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BibTeX
@article{salim2026effectiveness,
title = {{Effectiveness of Adding GLP‐1 Receptor Agonists to SGLT2 Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study}},
author = {Hussain Salim and Shaheer Qureshi and Gaurav S. Gulsin and Habib R. Khan and Saad Ahmed Waqas and Gerry P. McCann and Amit Garg and Mohammed Shurrab and Kamlesh Khunti and Muhammad Rashid},
journal = {Diabetes, Obesity \& Metabolism},
year = {2026},
month = sep,
doi = {10.1111/dom.71375},
url = {https://doi.org/10.1111/dom.71375},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effectiveness of Adding GLP‐1 Receptor Agonists to SGLT2 Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study
AU - Hussain Salim
AU - Shaheer Qureshi
AU - Gaurav S. Gulsin
AU - Habib R. Khan
AU - Saad Ahmed Waqas
AU - Gerry P. McCann
AU - Amit Garg
AU - Mohammed Shurrab
AU - Kamlesh Khunti
AU - Muhammad Rashid
PY - 2026
DA - 2026/09/27
JO - Diabetes, Obesity & Metabolism
DO - 10.1111/dom.71375
UR - https://doi.org/10.1111/dom.71375
AB - 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.
SN - 1462-8902
SN - 1463-1326
ER -