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Peer-reviewedCC BY-NC 4.0Diabetes, Obesity & Metabolism

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

1 more authors
4 affiliations
  1. 1Internal Medicine University of Manitoba College of Medicine Winnipeg Manitoba Canada
  2. 2Chronic Disease Innovation Centre (CDIC) Winnipeg Manitoba Canada
  3. 3Neil John Maclean Health Sciences Libraries University of Manitoba Winnipeg Manitoba Canada
  4. 4US Medical Affairs, Bayer US LLC Whippany New Jersey USA

Abstract

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.

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BibTeX
@article{perry2026effects,
  title = {{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}},
  author = {Frances Perry and Silvia J. Leon and Kate Polecina and Ruth Getachew and Nicole Askin and Thomas Ferguson and Reid Whitlock and Zihe Zheng and Carolina Aldworth and Arvind Katta and Jacob Earl and Mauricio Beller Ferri and Navdeep Tangri},
  journal = {Diabetes, Obesity \& Metabolism},
  year = {2026},
  month = sep,
  doi = {10.1111/dom.71337},
  url = {https://doi.org/10.1111/dom.71337},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - 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
AU  - Frances Perry
AU  - Silvia J. Leon
AU  - Kate Polecina
AU  - Ruth Getachew
AU  - Nicole Askin
AU  - Thomas Ferguson
AU  - Reid Whitlock
AU  - Zihe Zheng
AU  - Carolina Aldworth
AU  - Arvind Katta
AU  - Jacob Earl
AU  - Mauricio Beller Ferri
AU  - Navdeep Tangri
PY  - 2026
DA  - 2026/09/13
JO  - Diabetes, Obesity & Metabolism
DO  - 10.1111/dom.71337
UR  - https://doi.org/10.1111/dom.71337
AB  - 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.
SN  - 1462-8902
SN  - 1463-1326
ER  -