Abstract
Objective: Diabetes mellitus encompasses chronic metabolic disorders marked by impaired insulin secretion, action, or both, with type 1 and type 2 diabetes presenting distinct mechanisms and therapeutic needs. Achieving durable glycemic control remains essential to preventing microvascular and macrovascular complications. Data Sources: The growing prevalence of obesity among people with diabetes-driven by insulin resistance, lifestyle factors, and, in type 1 diabetes, insulin-associated weight gain-has increased the demand for therapies targeting both glycemia and body weight. Study Selection and Data Extraction: Traditional agents such as insulin, metformin, sulfonylureas, and thiazolidinediones have long served as treatment foundations but are limited by risks like hypoglycemia and weight gain. Incretin-based therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, have reshaped diabetes care by improving glycemic control, promoting weight loss, and offering cardiovascular and renal protection. Data Synthesis: Newer dual and multiagonists, including tirzepatide and emerging triple agonists, show unprecedented reductions in HbA(1c) and body weight, approaching outcomes seen with bariatric surgery. However, rising off-label use of antidiabetic drugs for weight loss raises safety concerns, including gastrointestinal effects and rare motility disorders, underscoring the need for careful patient selection and pharmacovigilance. Conclusion: Ongoing challenges include high costs, inequities in access, medication shortages, and the need for sustained pharmacovigilance. Future directions involve oral non-peptide incretin mimetics, broader indications for multiagonists, and deeper understanding of long-term safety, particularly in off-label contexts.