Micronutrient Risks During Second‑Generation Incretin Therapy

The narrative review Micronutrient Risks During Second‑Generation Incretin Therapy describes obesity as a setting where micronutrient shortfalls can coexist with excess energy intake, and it places newer incretin-based anti-obesity pharmacotherapies in that baseline context. The authors discuss second-generation agents including semaglutide and tirzepatide, noting that appetite suppression and gastrointestinal effects that support weight loss may also shift food exposure and tolerance in ways that could influence nutrient intake and biochemical markers. The review summarizes baseline vulnerabilities, therapy-era evidence signals, and the authors’ risk-stratified monitoring framework.

Baseline vulnerability, as presented by the authors, includes lower circulating 25-hydroxyvitamin D (described as among the most consistently reported findings in obesity), frequently altered iron handling, lower serum carotenoids reported in cohorts with obesity, and lower serum zinc concentrations. For vitamin D, the review frames lower 25-hydroxyvitamin D as potentially related to volumetric dilution and adipose sequestration, rather than necessarily reflecting low total-body stores. For iron, the authors highlight chronic low-grade inflammation as a proposed driver via higher hepcidin expression, with downstream effects on intestinal absorption and mobilization from stores. In the authors’ telling, this background matters because therapy-associated changes can be difficult to interpret without pre-treatment status.

During incretin-based therapy, the review compiles largely indirect evidence streams, including diagnostic-code/claims analyses, dietary intake studies, pharmacovigilance, small mechanistic or observational investigations, and rare case reports. In a large retrospective claims study summarized by the authors, nutrition-related diagnoses were recorded in 12.7% of patients at 6 months and 22.4% at 12 months after treatment initiation, with the review noting that detection may be influenced by surveillance intensity. The authors also describe pharmacovigilance signals in which dehydration is frequently reported early after initiation, and they summarize dietary studies reporting widespread micronutrient inadequacies relative to reference intakes. The review presents these as converging signals rather than definitive incidence estimates of biochemical deficiency.

The authors outline plausible pathways linking incretin therapy to altered micronutrient exposure or status, starting with reduced overall intake and fewer eating occasions, and extending to reduced meal variety and displacement away from micronutrient-rich food groups as portions shrink. They also describe gastrointestinal effects—including nausea and delayed gastric emptying—as contributors to reduced tolerance and altered timing of nutrient delivery, alongside the possibility of altered absorption for selected nutrients. As a specific pilot example, the review reports attenuated oral iron absorption after semaglutide initiation in an oral iron absorption test (median reduction of 13% after 10 weeks). The review also notes concomitant drug considerations such as metformin’s association with vitamin B12 in relevant populations, presenting these mechanisms as plausible rather than proven.

For monitoring, the authors describe a risk-stratified approach centered on dietary assessment and attention to diet quality within lower-energy intake, rather than assuming uniform deficiency risk across all treated patients. In the review’s framework, higher-risk patients are characterized by factors such as more pronounced or rapid weight loss, persistent gastrointestinal intolerance, restrictive or low-variety intake patterns, or pre-existing vulnerability, and the authors describe targeted laboratory testing in that context. When discussing monitoring, the authors note that targeted laboratory assessment may include markers such as ferritin/iron indices, 25-hydroxyvitamin D, and vitamin B12 in selected higher-risk situations, and they describe follow-up timing (for example, around 6–12 months) rather than a single universal schedule. The authors frame this as a synthesis of where vigilance may be most relevant during therapy.

Key Takeaways:

• The authors describe baseline micronutrient vulnerability in obesity that commonly includes lower circulating 25-hydroxyvitamin D, altered iron handling, lower carotenoids, and reduced serum zinc.
• The review summarizes indirect therapy-era signals from claims analyses, dietary intake studies, pharmacovigilance findings, and smaller mechanistic/observational investigations, presenting these as associations and signals rather than definitive outcome rates.
• The review describes a risk-stratified approach that emphasizes dietary assessment, considers selective labs (ferritin/iron indices, 25-hydroxyvitamin D, vitamin B12) in higher-risk patients, and discusses lean mass and protein adequacy as components of nutritional status characterization.