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 (HbA_1c) 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.

Background/Objectives: Gestational diabetes mellitus (GDM) represents one of the most common pregnancy-related disorders and it is correlated to increased risks of adverse maternal and neonatal outcomes. The prognostic role of initial glycemic values in predicting neonatal hypoglycemia and other complications remains underexplored. Methods: This retrospective study analyzed 233 women diagnosed with GDM between 2018 and 2024. Participants were stratified into three risk groups based on diagnostic oral glucose tolerance test (OGTT) values: low-risk group (fasting plasma glucose [FPG] 92–100 mg/dL, 1 h < 180 mg/dL, 2 h < 153 mg/dL), intermediate-risk group (FPG 101–110 mg/dL or 1 h 180–190 mg/dL or 2 h 153–163 mg/dL), and high-risk group (FPG > 110 mg/dL or 1 h > 190 mg/dL or 2 h > 163 mg/dL). Neonatal hypoglycemia was defined as the primary outcome, whereas secondary outcomes comprised insulin requirements, continuous glucose monitoring (CGM) use, macrosomia, polyhydramnios, and perinatal complications. Results: Non-significant differences across groups were observed except for Caucasian predominance in the high-risk group. Hypoglycemia trended higher in intermediate- and high-risk groups (26% and 21% vs. 17%), as well as polyhydramnios (14.3% and 13.8% vs. 4.5%) without statistical significance. Overall metabolic control was excellent, with almost 70% of patients maintaining HbA1c values ≤ 5.5% throughout the pregnancy with early and limited use of insulin therapy (17.3%). Conclusions: Diagnostic OGTT stratification provides limited prognostic value in optimized GDM care with early CGM and insulin use. Although trends for hypoglycemia and polyhydramnios suggest potential utility, the excellent metabolic control likely flattened the differences between groups. Prospective trials with CGM metrics are needed to develop more refined risk models, potentially enabling a more personalized management.

Type 1 diabetes (T1D) is an autoimmune disease in which genetic susceptibility interacts with environmental and immunometabolic factors. Growing evidence implicates gut dysbiosis, impaired intestinal barrier integrity, and altered microbial metabolites in the loss of immune tolerance and β-cell autoimmunity. Microbiota-derived metabolites regulate enteroendocrine glucagon-like peptide-1 (GLP-1) secretion, epithelial barrier function, and immune responses. Conversely, GLP-1 signaling and incretin-based therapies may modify the intestinal environment and microbial composition. Overall, the GLP-1–gut microbiota axis is a promising therapeutic target. Activation of the GLP-1 receptor suppresses pro-inflammatory pathways while promoting anti-inflammatory ones; all these effects may protect β-cells. Caveolin-1 may represent a molecular hub linking the GLP-1–gut microbiota–autoimmunity axis in T1D. This narrative review examines the bidirectional relationship between GLP-1 signaling and the gut microbiota and its potential relevance to T1D.