Frances Perry, Silvia J Leon, Kate Polecina, Ruth Getachew, Nicole Askin, Thomas Ferguson, Reid Whitlock, Zihe Zheng, Carolina Aldworth, Arvind Katta, Jacob Earl, Mauricio Beller Ferri, Navdeep Tangri
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.
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.