Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study
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OBJECTIVE: To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT). RESEARCH DESIGN AND METHODS: We randomized 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200–5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs. RESULTS: The effects of dapagliflozin on the primary composite outcome were consistent across GLT classes and according to the number of GLTs (all interaction P > 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54–0.96; P = 0.025). CONCLUSIONS: Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.
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In the three kidney outcomes trials examining SGLT2 inhibitors, the use of GLP-1 receptor agonists was rare, below 5%.
“In the three kidney outcomes trials examining SGLT2i, the use of GLP-1 RAs was rare, below 5%12–14.”
From Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial (2024) · cites this paper as [12]
The Conclusions state that GLP-1 receptor agonist use in DAPA-CKD was low. Our copy does not establish that use was below 5% in DAPA-CKD or report GLP-1 receptor agonist use across all three kidney outcomes trials. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOnly one of the three kidney outcomes trials published data on the GLP-1 receptor agonist subgroup (n = 122 of 4,304) and found no interaction of GLP-1 receptor agonist use with SGLT2 inhibitor benefits on main outcomes.
“Only one of these three trials, to our knowledge, published data on the GLP-1 RA subgroup (n = 122 of 4,304) and found no interaction of GLP-1 RA use with SGLT2i benefits on main outcomes12.”
From Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial (2024) · cites this paper as [12]
The Methods include GLP-1 receptor agonists in the DAPA-CKD subgroup analysis, and the Results report no effect modification by baseline glucose-lowering therapy class for the primary outcome, with similar benefits for secondary outcomes. The Methods give the trial total as 4,304, but our copy does not establish that 122 participants used GLP-1 receptor agonists. It also does not establish the citing authors’ comparison with the other two kidney trials. (LLM, conf=0.86)
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- Authors
- Beernink, J. M., Persson, F., Jongs, N., Laverman, G. D., Chertow, G. M., McMurray, J. J. V., Langkilde, A. M., Correa-Rotter, R., Rossing, P., Sjöström, C. D., Toto, R. D., Wheeler, D. C., & Heerspink, H. J. L.
- Affiliations
- University Medical Center Groningen (NL)
- Steno Diabetes Center Copenhagen (DK)
- University of Twente (NL)
- Stanford Medicine (US)
- University of Glasgow (GB)
- AstraZeneca (Sweden) (SE)
- 7The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico
- University of Copenhagen (DK)
- The University of Texas Southwestern Medical Center (US)
- University College London (GB)
- Corresponding author
- Heerspink, Hiddo J.L.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-01-20
- Volume
- 46
- Issue
- 3
- Pages
- 602-607
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10020024
- OpenAlex
- W4317548983
- Cited by
- 18
- References
- 21
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 5
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- University of Twente Research Information (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- University of Twente Research Information (submittedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- dapagliflozin, type 2 diabetes, chronic kidney disease, glucose-lowering therapy, SGLT2 inhibitors, DAPA-CKD trial, estimated glomerular filtration rate decline, end-stage renal disease, cardiovascular events, insulin initiation, drug interactions
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Adult, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucosides, Heart Failure, Humans, Renal Insufficiency, Chronic
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