Effects of Renin-Angiotensin Inhibitors, Sodium-Glucose Cotransporter 2 Inhibitors, Mineralocorticoid Receptor Antagonists and Glucagon-Like Peptide 1 Receptor Agonists on Kidney Outcomes in Patients With Type 1 Diabetes: A Systematic Review and Meta-Analysis.
Frances Perry, Silvia J Leon, Kate Polecina et al.
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In 30 seconds
This systematic review and meta-analysis assessed kidney outcomes and safety of renin-angiotensin system inhibitors (RASis), SGLT-2 inhibitors, MRAs and GLP-1 receptor agonists in adults with type 1 diabetes. It included 41 randomised controlled trials. Across treatments, UACR was reduced by 45% versus placebo (GMR = 0.55; 95% CI: 0.32-0.94), a result driven predominantly by SGLT-2 inhibitor studies; evidence for RASis was limited and non-significant in subgroup analysis. No drug class showed a difference in annual eGFR change versus placebo. Treatment was associated with higher risks of hypoglycaemia and diabetic ketoacidosis.
Key findings
- SGLT-2 inhibitors and RASis were associated with a 45% UACR reduction versus placebo (GMR = 0.55; 95% CI: 0.32-0.94), predominantly driven by SGLT-2 inhibitor studies.
- Annual eGFR change did not differ across drug classes versus placebo (mean difference 1.16 mL/min/1.73 m 2 /year; 95% CI: -0.38 to 2.70).
- Treatment was associated with increased hypoglycaemia risk (RR = 1.03; 95% CI: 1.01-1.05) and DKA risk (RR = 1.97; 95% CI: 1.33-2.93).
- No trials of non-steroidal or other MRAs met the inclusion criteria.
Why it matters
Kidney-protective treatment options for type 1 diabetes remain limited, and these pooled findings suggest possible albuminuria benefit while showing no detectable eGFR benefit. The associated risks of hypoglycaemia and DKA are important when interpreting potential benefits. The results also highlight that evidence across drug classes is uneven and that dedicated trials are needed to clarify efficacy and safety.
What to keep in mind
The evidence is limited by the absence of eligible MRA trials and by limited, non-significant evidence for RASis in subgroup analysis. The pooled analysis found no difference in annual eGFR change.