Key result
SGLT-2i or RASi treatment cuts UACR by ~45% versus placebo in Type 1 diabetes.
Why the study?
Treatment options for chronic kidney disease in Type 1 diabetes mellitus have remained unchanged for 30 years, limited to renin–angiotensin system inhibitors, despite advances in Type 2 diabetes therapies.
Do RASis, SGLT-2is, MRAs, and GLP-1RAs improve UACR and eGFR in adults with Type 1 diabetes mellitus?
Meta-Analysis
Do RASis, SGLT-2is, MRAs, and GLP-1RAs improve UACR and eGFR in adults with Type 1 diabetes mellitus?
Effect estimate: GMR 0.55 (95% CI 0.32-0.94)
In adults with Type 1 diabetes, SGLT-2 inhibitors and RAS inhibitors significantly reduce albuminuria but do not change the annual rate of eGFR decline, while increasing the risk of hypoglycemia and diabetic ketoacidosis.
Supports albuminuria reduction with SGLT-2i or RASi in type 1 diabetes; extends T2D renoprotection data but leaves hard-outcome trials open.
Aims While the new kidney protective therapies have transformed chronic kidney disease (CKD) management in patients with Type 2 diabetes mellitus (T2DM), treatment options for CKD in Type 1 diabetes mellitus (T1DM) have remained unchanged for 30 years, limited to renin–angiotensin system inhibitors (RASis). Given similarities in pathophysiology between CKD in T1DM and T2DM, we conducted a systematic review and meta‐analysis evaluating sodium–glucose cotransporter‐2 inhibitors (SGLT‐2is), mineralocorticoid receptor antagonists (MRAs) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on kidney function, albuminuria and safety outcomes. Materials and Methods We searched Medline, EMBASE, Cochrane CENTRAL, CINAHL, Global Health, LILACS and Scopus from inception until 11 April 2025, for randomised controlled trials (RCTs) evaluating RASi, MRAs, GLP‐1RAs and SGLT‐2is on change in urine albumin‐to‐creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in adults (age ≥ 18) with T1DM. Results A total of 7151 unique records were identified and 41 RCTs were included in the meta‐analysis. No RCTs evaluating nsMRAs or MRAs met our inclusion criteria. Treatment with SGLT‐2i or RASi was associated with a 45% reduction in UACR versus placebo (GMR = 0.55; 95% CI: 0.32–0.94). No difference in the annual rate of eGFR change was observed across drug classes compared to placebo (mean difference 1.16 mL/min/1.73 m 2 /year; 95% CI: −0.38 to 2.70). Treatment was associated with a higher risk of hypoglycaemia (RR = 1.03; 95% CI: 1.01–1.05) and DKA (RR = 1.97; 95% CI: 1.33–2.93). Conclusions In patients with T1DM, the pooled analysis showed a reduction in UACR overall, but that this appeared to be driven predominantly by the SGLT‐2i studies, with limited and non‐significant evidence in the RAS inhibitor subgroup. Dedicated RCTs in the T1DM population could help establish the efficacy and safety of these different drug classes. Trial Registration PROSPERO registration: CRD420261352699.
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Perry et al. (2026) conducted a meta-analysis in Type 1 diabetes mellitus. SGLT-2 inhibitors and RAS inhibitors vs. Placebo was evaluated on Change in urine albumin-to-creatinine ratio (UACR) (GMR 0.55, 95% CI 0.32-0.94). Treatment with SGLT-2 inhibitors or RAS inhibitors was associated with a 45% reduction in urine albumin-to-creatinine ratio versus placebo in adults with Type 1 diabetes (GMR 0.55; 95% CI 0.32-0.94).
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