GLP-1-Based Therapy in Type 1 Diabetes: Balancing Efficacy, Safety, and Patient Selection

To critically examine the evolving evidence on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide as adjuncts to insulin therapy in type 1 diabetes (T1D), with particular emphasis on their benefit-risk balance in individuals with overweight or obesity.

This narrative review examines evidence on liraglutide, semaglutide and tirzepatide in T1D, focusing on effects on body weight and insulin requirements, alongside hypoglycaemia, ketosis, diabetic ketoacidosis and gastrointestinal tolerability.

Early trials with liraglutide demonstrated reductions in body weight and insulin requirements but raised concerns regarding hypoglycaemia and ketosis. More recently, semaglutide and tirzepatide have renewed interest in incretin-based therapy in T1D, particularly among individuals with obesity. Their greater effects on weight and insulin requirements introduce a clinically important safety challenge: insulin must be reduced sufficiently to prevent hypoglycaemia while maintaining adequate insulinization to suppress lipolysis and ketogenesis. Gastrointestinal adverse events may further destabilize this balance through reduced carbohydrate intake and dehydration.

Current evidence supports a phenotype-directed approach centred primarily on adults with T1D and obesity, accompanied by careful patient selection, individualised insulin adjustment, glucose and ketone monitoring, and structured patient education. The clinical question has shifted from whether GLP-1-based therapies are effective in T1D to which patients are most likely to achieve a favourable benefit-risk balance and how these therapies can be used safely.