Metabolic dysfunction and the use of adjunct medications in type 1 diabetes

Type 1 diabetes is increasingly complicated by obesity and broader metabolic dysfunction, yet there are barriers to the use of adjunctive pharmacotherapies in this population. This review evaluates the evidence for metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) in type 1 diabetes, with a focus on weight loss, glycaemic control, insulin dose requirements and safety.

Despite advances, metformin remains the only adjunct widely endorsed in national guidelines for adults with type 1 diabetes. In clinical trials, GLP-1RAs used alongside automated insulin delivery systems demonstrate significant improvements in weight, glucose sensor time-in-range, and total daily insulin dose, without increased risk of diabetic ketoacidosis (DKA). SGLT2i produce more modest weight and HbA1c improvements, and may be associated with an increased risk of DKA, although they have a clear evidence base for independent cardiovascular benefits.

There is an increasing demand by patients and desire by physicians to utilize adjunctive medications in type 1 diabetes. Many patients with type 1 diabetes who are highly likely to benefit from the weight loss and cardiorenal risk reduction effects of these drugs are denied access to them because of putative safety concerns and a dearth of clinical trial evidence in type 1 diabetes. Identifying patients with type 1 diabetes most likely to tolerate and benefit from these agents is a research priority. Real world datasets accounting for the increased off license use of these drugs offers an opportunity to rapidly develop evidence-based guidance.