Precision medicine in type 2 diabetes: targeting SGLT2 inhibitor treatment for kidney protection
Main finding · Kidney disease progressionResult — go to the resultHazard ratio 0.58 95% CI 0.48–0.69Authors' conclusion
A model adapting the international CKD-PC risk score can accurately predict the individual-level kidney protection benefit from treatment with SGLT2 inhibitors in people with type 2 diabetes and no or early-stage CKD. This could guide treatment decisions in clinical practice worldwide and could target treatment more effectively than the ≥3 mg/mmol albuminuria threshold recommended by current international guidelines.
Study context
- Population
- Adults with T2D, eGFR ≥60 ml/min per 1.73 m² and urinary albumin/creatinine ratio (uACR) <30 mg/mmol, without HF or atherosclerotic vascular disease, UK primary care (Clinical Practice Research Datalink, 2013–2020)treatment initiations
- Participants
- 53,096 vs 88,404
- Exposure
- SGLT2i vs DPP-4i/SU
- SGLT2 inhibitorsn = 53,096
- DPP4 inhibitors/sulfonylureasn = 88,404reference
- Outcome
- Kidney disease progression (≥50% eGFR decline, end-stage kidney disease or kidney-related death)
Methodological detailsoverlap-weighted Cox proportional hazards models, prediction model development and validation
- Overlap-weighted Cox proportional hazards models
- Prediction model development and validation
Main finding
Kidney disease progression
Hazard ratio
0.58
95% CI 0.48–0.69
As reported in the abstract
Observational data: associations, not effects.
Further findings
Calibration of CKD-PC risk score
- Did not require recalibration; calibration slope
- 1.05 (95% CI 0.94, 1.17)
Model-predicted absolute risk reduction with SGLT2i · 3 years
- Median overall predicted absolute risk reduction (IQR 0.26-0.55)
- 0.37%
- Calibration slope
- 1.10 (95% CI 1.09, 1.12)
Clinical utility: model-based targeting vs ≥3 mg/mmol albuminuria threshold (same proportion targeted, n=25,303, 17.9%) · 3 years
- Events prevented, model-based vs albuminuria threshold
- 253 vs 228
- Subgroup of individuals with uACR <3 mg/mmol identified with greater absolute risk reduction
- 6.7%
- Absolute risk reduction, identified subgroup vs remainder with uACR <3 mg/mmol (extended 5 year observational analyses), p=0.05
- 3.2% vs 1.2%
Original publication
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