GLP-1 and dual incretin agonists linked to multifactorial micronutrient risk in obesity management

Obesity management has been revolutionized by GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, achieving significant weight loss. These therapies primarily act via appetite suppression, reduced energy intake, and gastrointestinal effects. However, these mechanisms may also modify dietary intake and physiology, raising concerns about potential micronutrient disturbances during long-term treatment. Understanding these risks is crucial for optimizing patient care and preventing deficiencies, addressing a key gap in current treatment protocols.

This narrative clinical review synthesized evidence on mechanistic pathways, clinical signals, and monitoring considerations related to micronutrient risk during incretin-based obesity pharmacotherapy. Evidence was integrated from diverse sources, including dietary studies, observational cohorts, mechanistic investigations, clinical trials, and pharmacovigilance reports. The review also incorporated literature on obesity-related micronutrient physiology to provide a comprehensive understanding of the interplay between these factors and the impact of GLP-1 receptor agonists and GIP/GLP-1 receptor agonists.

Micronutrient vulnerability appears to arise from a complex interaction of factors, including reduced food intake, lower dietary diversity, gastrointestinal intolerance, delayed gastric emptying, rapid weight loss, and baseline nutritional risk. The most relevant signals involve hematologic, fat-soluble, bone-related, trace element, and electrolyte domains. Specifically, iron, vitamin B12, vitamin D, calcium, magnesium, and zinc are highlighted as primary concerns. Additional context-dependent concerns include thiamine, folate, vitamin A, other fat-soluble vitamins, and potassium. Most abnormalities reported to date are subclinical or indirect, but clinically meaningful consequences may occur in susceptible individuals, such as those with prior bariatric surgery, gastrointestinal disorders, poor baseline diet quality, older age, or prolonged nausea and vomiting. This multifactorial risk underscores the need for personalized approaches.

Micronutrient risk during incretin-based obesity pharmacotherapy is likely multifactorial and patient-specific, necessitating individualized assessment.