Risk of Nephrolithiasis Associated With SGLT2 Inhibitors Versus DPP4 Inhibitors Among Patients With Type 2 Diabetes: A Target Trial Emulation Study
Authors' conclusion
We found a lower risk of nephrolithiasis associated with SGLT2is versus DPP4is in stone never- and ever-formers. Despite a greater relative risk reduction in the former, the absolute risk reduction was greater in the latter.
Study context
- Population
- Patients with T2D, Korea National Health Insurance Service database 2010–2021, stone never- and ever-formers17,006 propensity score (PS)-matched pairs
- Exposure
- SGLT2i vs DPP4i initiators
- Outcome
- Incident nephrolithiasis
- Follow-up
- Mean 654 days
Methodological detailstarget trial emulation, active comparator new-user, 1:1 propensity score matched, stratified by stone never- and ever-formers, negative control outcome
- Target trial emulation
- Active comparator new-user
- 1:1 propensity score matched
- Stratified by stone never- and ever-formers
- Negative control outcome
Main finding
As reported in the abstract
SGLT2i
0.65 events per 100 person-years
DPP4i
1.12 events per 100 person-years
SGLT2i vs DPP4iHazard ratio (95% CI)
Pooled; PS-matched
0.54(0.50–0.57)
- Pooled; lower with SGLT2i
- Incidence rate difference (IRD) −0.46 (95% CI −0.21 to −0.52)
- Stone never-formers: HR
- 0.43 (0.39-0.48) (95% CI)
- Stone never-formers: IRD
- −0.32 (−0.27 to −0.36) (95% CI)
- Stone ever-formers: HR
- 0.64 (0.59-0.69) (95% CI)
- Stone ever-formers: IRD
- −2.26 (−1.77 to −2.76) (95% CI)
Observational data: associations, not effects.
Further findings
Osteoarthritis encounters (negative control outcome)
- Near-null associations
Nephrolithiasis by sex, age, thiazide co-use and baseline CV risk
- Results consistent across subgroups
Original publication
Risk of Nephrolithiasis Associated With SGLT2 Inhibitors Versus DPP4 Inhibitors Among Patients With Type 2 Diabetes: A Target Trial Emulation Study. Diabetes Care. Published 12 December 2024. doi:10.
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