Comparative effectiveness of sulfonylureas on kidney outcomes in adults with type 2 diabetes and moderate cardiovascular risk: a target trial emulation
Authors' conclusion
Glyburide was associated with a modestly lower risk of kidney complications, despite a higher risk of hypoglycemia, while glipizide was associated with a higher risk of kidney complications. These hypothesis-generating findings suggest important within-class differences that warrant consideration in clinical decision-making and future research. Despite rigorous prespecified causal inference analytic methods, the risk of unmeasured confounding and bias by indication with the use of observational data remains.
Study context
- Population
- Adults ≥21 years with T2D at moderate cardiovascular risk; commercial, Medicare Advantage and traditional Medicare claims, 2014–2021weighted cohort
- Participants
- 295,092 adults
- Exposure
- Initiation of glimepiride vs glipizide vs glyburide
- Glimepiriden = 134,926
- Glipiziden = 145,984
- Glyburiden = 14,182
- Outcome
- Incident chronic kidney disease (CKD) stage 3 or worse, including initiation of kidney replacement therapy
Methodological detailsretrospective cohort study using claims data, propensity scores estimated by super learner ensemble, inverse probability of treatment weighting, proportional hazards models
- Retrospective cohort study using claims data
- Propensity scores estimated by super learner ensemble
- Inverse probability of treatment weighting
- Proportional hazards models
Main finding
As reported in the abstract
CKD stage 3 or worse (kidney complications) · 1 year after treatment initiation
Hazard ratio (95% CI)
Glyburidevs Glimepiride
0.84(0.76–0.92)
Glyburidevs Glipizide
0.81(0.73–0.89)
Glipizidevs Glimepiride
1.04(1.00–1.07)
Observational data: associations, not effects.
Safety
| Outcome | HR (95% CI) | |
|---|---|---|
| Severe hypoglycemiaGlyburidevs Glipizide | 1.47 (1.27–1.71) | |
| Severe hypoglycemiaGlyburidevs Glimepiride | 1.22 (1.05–1.42) | |
| 0.512Hazard ratio (log scale) |
Original publication
Comparative effectiveness of sulfonylureas on kidney outcomes in adults with type 2 diabetes and moderate cardiovascular risk: a target trial emulation. BMJ Open Diabetes Res Care. Published 21 May 2026. doi:10.
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