GLP-1 and GIP in Type 1 Diabetes Therapy: A Time for Reappraisal?

Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are essential regulators of glucose homeostasis, energy balance, and metabolic communication between organs. While therapies based on incretins are well established for type 2 diabetes (T2DM), their physiological significance and therapeutic potential in type 1 diabetes (T1DM) are less understood. In T1DM, the autoimmune destruction of pancreatic β-cells greatly reduces but does not abolish insulin production. However, various extrapancreatic actions of incretins continue, including effects on gastric emptying, glucagon secretion, appetite, inflammation, and cardiovascular function. The increasing prevalence of overweight, obesity, and insulin resistance among individuals with T1DM has heightened interest in exploring incretin-based treatments as adjuncts to insulin therapy. Data from randomized controlled trials, retrospective cohorts, and mechanistic studies were analyzed. This narrative review synthesizes available experimental, clinical trial, and real-world evidence on the physiology of incretins, their altered actions in T1DM compared with T2DM, and the effects of GLP-1 receptor agonists (GLP-1RAs) and tirzepatide, a dual GIP/GLP-1 agonist, on glycemic control, body weight, and cardiovascular outcomes in patients with T1DM. The use of GLP-1RAs in T1DM showed a weight reduction between 3.6 kg and 8.8 kg and improved glycated hemoglobin (HbA1c) by 0.2–0.8%, while treatment with tirzepatide for 6 months resulted in a body weight change of −10.3 to −10.6 kg. Growing evidence suggests a significant role of incretins in certain patients with T1DM, although large-scale, adequately powered randomized controlled trials are necessary to confirm their long-term efficacy and safety.