Diabetes, obesity & metabolism · 2026
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.
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Perry Frances, Leon Silvia J, Polecina Kate, Getachew Ruth, Askin Nicole, Ferguson Thomas, Whitlock Reid, Zheng Zihe, Aldworth Carolina, Katta Arvind, Earl Jacob, Beller Ferri Mauricio, Tangri Navdeep
Аннотация
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 m2/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.
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 m2/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.