SGLT inhibitors are established for heart and kidney protection in type 2 diabetes and in people without diabetes. In type 1 diabetes they are largely unavailable for that purpose, because the ketoacidosis risk stopped the earlier glycaemic programmes and no cardiorenal programme replaced them. This joint perspective from endocrinology, nephrology and cardiology sets out what would be needed to change that.
The argument has two parts. First, the mechanisms driving cardiorenal benefit in type 2 diabetes and in non-diabetic kidney disease are unlikely to depend on the aetiology of the diabetes, so the extensive evidence in those populations should be expected to translate. Second, and more consequentially for trial design, that expectation means registrational trials in type 1 diabetes might not need to be powered for event-based outcomes at all - suitable surrogate endpoints could make a feasible trial possible in a population too small to support a conventional cardiovascular outcome programme.
The condition attached is explicit and should not be skipped over. Ketoacidosis is the critical risk, mitigation protocols exist, and rigorous data on whether they actually work do not. So the roadmap is: feasible surrogate-endpoint trials, with ketoacidosis data collected as carefully as the efficacy data. For clinicians now, this is not a licence to prescribe off-label - it is a statement that the field has agreed on what the missing evidence is, which is usually the step before it arrives.
- This is an expert perspective and a research roadmap, not new trial evidence or a change in licensing.
- Do not read it as support for off-label SGLT inhibitor use in type 1 diabetes for cardiorenal protection.
- The unresolved question is whether ketoacidosis mitigation protocols work - that is what the authors say is missing.
- Where a patient with type 1 diabetes has chronic kidney disease or heart failure, the cardiorenal armamentarium remains what it was.
- Expect surrogate-endpoint registrational trials; know that a surrogate-based approval carries different certainty from an outcome-based one.
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