The Possible Hematological Cost of Metabolic Success: Do Incretin-Based Therapies Silently Trigger Anemia?

Abstract

Diabetes mellitus and obesity represent a growing global health burden with high morbidity and mortality. In the last several years, novel incretin-based therapies have been developed, and their use has risen dramatically. Beyond their proven metabolic, glycemic, cardiovascular, renal, and many other benefits, there are some observational data linking anemia development with their use. From the era of gliptins to retatrutide, in this review we tried to explore whether erythroid suppression is the hidden paradigm of advanced incretin-based therapies. Potential pathophysiological explanations include micronutrient vulnerabilities due to reduced food intake, lower dietary diversity, gastrointestinal intolerance, delayed gastric emptying, and weight loss. The most important concerns involve deficiencies in iron, vitamin B12, vitamin B2, vitamin D, calcium, magnesium, and zinc, along with others such as thiamine, folate, vitamin A, and potassium. The available evidence indicates a complex and heterogeneous relationship between incretin-based therapies and hematological parameters, with findings differing across therapies, study populations, and outcomes. Although observational studies suggest possible associations with anemia, iron deficiency, and nutritional deficiencies in selected populations, current evidence is insufficient to establish a direct causal relationship or a class-wide adverse effect. Further large-scale studies are needed, as well as increased clinician awareness of potential hematological and nutritional consequences that require laboratory follow-up before and during medication prescription.