Background/Objectives: Incretin-based medications have transformed obesity management by enabling substantial body weight reduction. However, the rapid and pronounced loss of body mass necessitates a comprehensive, multidisciplinary approach incorporating nutritional and physical activity strategies to preserve lean mass, optimize functional outcomes, and prevent long-term complications. This narrative review provides a critical overview of this emerging clinical concern, which is expected to gain increasing relevance in the coming years. Methods: A literature review was conducted up to 31 October 2025, focusing on studies addressing nutritional, physical activity, and adjunctive interventions in adults with obesity treated with incretin-based medications. Results: Incretin-based agents induce significant weight loss, comparable to bariatric surgery, predominantly targeting adipose tissue. Nevertheless, these medications also cause rapid reductions in muscle and bone mass, often accompanied by nutrient deficiencies, which may compromise metabolic health and physical function. Tailored nutritional strategies—including hypocaloric diets enriched in protein and fiber, as well as amino acid, vitamin, and mineral supplementation—are critical to preserve lean mass and support sustained weight maintenance. Concurrently, structured, supervised physical activity, encompassing aerobics, resistance, and strength training, mitigates muscle loss and enhances functional capacity. Emerging pharmacological agents designed to promote adipose tissue reduction while preserving lean mass, as well as interventions targeting gut microbiota modulation, may represent promising adjunctive strategies to optimize long-term outcomes further. Conclusions: While incretin-based medications produce substantial weight loss, their impact on lean mass underscores the necessity of integrating personalized nutrition, supplementation, and structured exercise to preserve muscle, prevent malnutrition, and optimize long-term health and obesity outcomes.

In the years immediately after its discovery, glucagon was considered only as an "antidote" for the treatment of insulin-induced hypoglycemia. The advent of specific radioimmunoassay (RIA) techniques has enabled a better understanding of glucagon's role, revealing its close connection with the pathogenesis of diabetes mellitus. This review briefly summarizes the studies regarding the pathophysiology of glucagon and its different therapeutic implications in metabolic disorders. A comprehensive literature search was conducted utilizing PubMed and Scopus, employing the keywords "glucagon", "insulin", "glucose counterregulation", and "diabetes mellitus". This search was restricted to studies published within the past fifteen years, without imposing limitations on study types. However, we mention certain historical aspects of the discovery of glucagon. In type 1 diabetes mellitus, research has concentrated on glucagon's role as a direct counterregulatory hormone to insulin, and on delineating the condition of "glucagon excess" in absolute insulin deficiency, considered a critical factor in the onset of diabetic ketoacidosis (DKA). Conversely, in type 2 diabetes mellitus, research has transitioned from glucagon antagonism to the "paradoxical" activity of glucagon agonism, given its potential positive effects on energy consumption. This has facilitated the development of incretin-based molecules with multi-receptor action, demonstrating significant clinical efficacy in glycemic control, weight loss, and hepatic fat diminution. This review highlights the fundamental role of glucagon in the pathogenesis of diabetes mellitus and its significant therapeutic implications, based on recent research findings.

Background/Objectives: Chronic constipation is a prevalent gastrointestinal (GI) disorder among individuals with diabetes mellitus (DM), occurring more often than in healthy subjects. This review provides a systematic overview of this often-underestimated clinical condition in people with DM. Methods: A narrative review of literature up to 30 May 2025 was conducted, focusing on studies regarding the pathogenesis of constipation in DM, the correlation with GLP-1 RAs treatment, and the diagnostic-therapeutic framework. Results: The mechanisms underlying constipation in DM remain largely unclear; however, a multifactorial etiology has been proposed, involving structural changes in various tissues within the GI tract wall, as well as functional abnormalities, often secondary to hyperglycemia. It is noteworthy that the use of GLP-1 RAs, a class of medications crucial for managing glycemic control and reducing cardiovascular and renal risk in type 2 DM, is another cause of constipation. The diagnosis of constipation is typically based on clinical evaluation, as validated methods for assessing colonic transit are invasive and available only in specialized centers. Treatment objectives include alleviating symptoms and restoring bowel function. The primary strategy for management involves dietary changes and physical activity. If the clinical response is inadequate, the use of laxatives is recommended. Finally, newer agents and mechanical methods may be considered for scenarios that are particularly severe. Conclusions: Given the increasing global prevalence of DM, healthcare professionals must recognize the clinical problem constituted by the occurrence of chronic constipation, especially considering the use of medications such as GLP-1 RAs that may induce this clinical condition.