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
https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.70506
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