Efficacy and safety of GLP-1 receptor agonists and SGLT2 inhibitors as adjuncts to insulin in type 1 diabetes: systematic review and meta-analysis

Abstract

Aims Adjunctive therapies to insulin for type 1 diabetes mellitus (T1DM), including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), may improve glycaemic control and reduce insulin requirements; however, safety concerns remain, particularly for diabetic ketoacidosis (DKA).Materials and Methods PubMed, Ovid MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library through 26 September 2025. Data were pooled using a random-effects model. Risk of bias analyses were performed.Results Ninety studies met inclusion criteria. GLP-1RAs produced modest improvements in glycaemic control, lowering glycated haemoglobin (HbA1c) (-0.56%) and increasing time-in-range (TIR), while reducing total and basal daily insulin requirements, body weight (-3.6 kg) and body mass index (BMI) (-1.05 kg/m2). Severe hypoglycaemia and DKA were rare; gastrointestinal adverse effects were the most common adverse effects; renal and cardiovascular outcomes were neutral. SGLT2is significantly improved HbA1c (-0.38%), TIR (+8.6 pp), insulin requirements (-4.7 U/day), body weight (-2.5 kg) and BMI (-0.82 kg/m2). Severe hypoglycaemia was uncommon, while DKA risk was increased (risk ratios = 2.19, 95% confidence interval 1.16-4.17), primarily in predictable clinical settings. Renal parameters remained stable or improved, and cardiovascular events were infrequent. Across drug classes, mortality and hospitalisations were rare.Conclusions Adjunctive GLP-1RAs and SGLT2is provide modest clinical improvements in adults with type 1 diabetes. These benefits must be balanced against class-specific safety concerns, especially the increased risk of DKA with SGLT2-based therapies. Larger, long-term trials are needed to define their optimal use in routine care.