Sema reduced major kidney events 24% in T2D + CKD. Stopped early for efficacy.
Trial design
Perkovic et al. (NEJM 2024): 3,533 adults with T2D and stage 2-4 CKD (eGFR 25-75 with elevated albuminuria). Sema 1.0 mg weekly vs placebo on standard ACE/ARB.
Results
- Composite kidney endpoint: HR 0.76 (24% reduction)
- Persistent ≥50% eGFR decline: HR 0.74
- Kidney failure: HR 0.80
- Kidney or CV death: HR 0.71
- All-cause mortality: HR 0.80
Stopped early. Median 3.4 years.
Mechanism
Direct renoprotective effects: reduced glomerular hyperfiltration, reduced oxidative stress, anti-inflammatory effects on renal interstitium, BP reduction.
Implications
- KDIGO 2024 guidelines now recommend GLP-1 RA in T2D + CKD
- GLP-1 + SGLT2 inhibitor biologically complementary
- FLOW used 1.0 mg — not the 2.4 mg used for weight