TIRZEPATIDE AS AN ADJUNCTIVE THERAPY IN TYPE 1 DIABETES MELLITUS WITH OVERWEIGHT OR OBESITY: EMERGING EVIDENCE AND CLINICAL CHALLENGES

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Introduction: Type 1 Diabetes Mellitus (DM1) is characterized by absolute insulin deficiency, with insulin therapy being the mainstay of treatment. However, a growing proportion of patients present with the "Double Diabetes" phenotype, characterized by overweight, insulin resista nce, and difficulty in glycemic control, which significantly increases cardiometabolic risk and long -term complications. Tirzepatide, a dual agonist of glucose- dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demon strated metabolic benefits in other clinical contexts, sparking interest as an adjunctive therapy in DM1. Its synergistic action promotes not only the regulation of glycemia, but also the reduction of appetite and the improvement of peripheral insulin sens itivity, arousing scientific interest as a promising adjuvant therapy for the management of type 1 diabetes mellitus (DM1) associated with obesity. Objective: To analyze the emerging evidence on the use of tirrizepatide as adjuvant therapy to insulin therapy in individuals with DM1, especially in the presence of overweight or obesity, identifying metabolic benefits and risks to patient safety. Methods: This is a narrative literature review, carried out through searches in scientific databases, including Pub Med and Scopus, using terms related to "Type 1 Diabetes Mellitus", "tirzepatide", "incretins", "GLP-1" and "GIP". Randomized clinical trials, observational studies, systematic reviews and research protocols published between 2021 and 2026 were selected, with emphasis on outcomes related to body weight and metabolic safety. Results: Preliminary studies suggest that tirzepatide may promote weight loss, improved glycemic parameters, and a decrease in the total daily insulin dose, especially basal insulin, reflecting an improvement in tissue insulin resistance induced by the GIP component of the molecule. However, the available evidence is still limited, with small sample sizes, short follow -up times, and specific populations. Furthermore, safety concerns are hi ghlighted, including the risk of hypoglycemia, ketosis, and euglycemic diabetic ketoacidosis, especially when insulin therapy is inadequately reduced. This occurs because a sharp reduction in insulin doses, motivated by weight loss and glycemic improvement, may result in insufficient circulating insulin levels to suppress lipolysis and hepatic ketogenesis, even with apparently controlled glucose levels. Conclusion: Tirzepatide represents an innovative therapeutic strategy as an adjunct in the management of type 1 diabetes in selected patients, but it is not yet fully established. Its use should be interpreted with caution and restricted to research or specialized monitoring contexts, with further studies needed to define its efficacy, safety, and clinical ap plicability. Robust clinical trials are necessary to define safe protocols and dose adjustments and to ensure that the metabolic benefits outweigh the acute risks of ketoacidosis complications.