Abstract
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established for the treatment of type 2 diabetes but are not currently recommended for the treatment of people with type 1 diabetes. However, during the last decade experience has been collected regarding addition of a GLP-1 RA to insulin in patients with type 1 diabetes, both from clinical trials and off-label use. Several retrospective as well as prospective observational studies without a control group have been published. Only very few placebo-controlled, randomized studies have been presented. The present narrative review assesses the efficacy and safety of the different GLP-1 RAs and the dual GLP-1/ glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide on glycaemic control, body weight, dose of insulin and adverse events in people with type 1 diabetes.
The reduction in HbA1c has in most studies been absent or minimal (0-0.3% (3.3 mmol/mol)), partly explained by a concomitant significant reduction in dose of insulin. The reduction in body weight has been in the range of 2-7 kg. The most pronounced reduction in body weight and dose of insulin has been obtained with semaglutide and tirzepatide. In the two largest placebo-controlled, randomized studies infrequent increases in hyperglycaemia with ketosis and hypoglycaemia were registered. The only identified clinical variable impacting the effect of GLP-1 RAs on HbA1c and dose of insulin has been residual beta-cell function. Treatment with GLP-1 based therapy was associated with more gastrointestinal adverse events. The outcomes of the studies depended on the different GLP-1 RAs applied, the intervention time and the residual beta-cell function.
Thus, combination therapy is of interest in relation to weight loss in people with obesity and type 1 diabetes, and in newly diagnosed patients with residual beta-cell function aiming at prolonging remission period. More well-designed studies of high quality are of required to better identify the subgroups, who will benefit most from adding GLP-1 based therapy to insulin in people with type 1 diabetes.