A systematic review and meta-analysis published in Diabetes, Obesity & Metabolism pooled 41 randomized controlled trials to ask whether the kidney drugs that reshaped type 2 diabetes care do anything measurable in type 1 diabetes. The answer is a qualified yes on albuminuria and a clear warning on safety.

The drug classes examined were renin-angiotensin system inhibitors (RASis), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), mineralocorticoid receptor antagonists (MRAs) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), the same family as semaglutide and tirzepatide. The outcomes were urine albumin-to-creatinine ratio (UACR), a marker of protein leaking into urine, and estimated glomerular filtration rate (eGFR), a measure of how much blood the kidneys are filtering.

Thirty years without a new option

The authors frame the problem bluntly: chronic kidney disease treatment in type 1 diabetes has not changed in 30 years and remains limited to RAS inhibitors, while type 2 diabetes has acquired several new protective therapies. Their rationale for pooling the evidence is that the underlying kidney pathology in the two conditions looks similar.

Key results

From 7,151 unique records the researchers included 41 randomized trials in adults aged 18 and over. Treatment with an SGLT-2i or RASi was associated with a 45% reduction in UACR versus placebo (GMR 0.55; 95% CI 0.32 to 0.94).

The filtration numbers did not move. Across drug classes there was no difference in the annual rate of eGFR change compared with placebo (mean difference 1.16 mL/min/1.73 m2/year; 95% CI minus 0.38 to 2.70). Treatment was also associated with a higher risk of hypoglycemia (RR 1.03; 95% CI 1.01 to 1.05) and of diabetic ketoacidosis (RR 1.97; 95% CI 1.33 to 2.93).

Limitations

No trials of MRAs or nonsteroidal MRAs met the inclusion criteria at all, so one of the four classes in the question is simply absent from the answer. The authors also note the UACR signal appeared to be driven predominantly by the SGLT-2i studies, with limited and non-significant evidence in the RAS inhibitor subgroup, which is an awkward finding given RAS inhibition is the current standard. Pooled surrogate markers are not the same as hard kidney outcomes.

Bottom line

The authors conclude that dedicated randomized trials in the type 1 population could help establish the efficacy and safety of these classes. Until those exist, an albuminuria benefit borrowed from type 2 evidence has to be weighed against a near-doubled ketoacidosis risk signal.