Interaction Between Metabolic Diseases, GLP-1 Receptor Agonists, and Helicobacter pylori Infection: An Updated Evidence Summary
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INTRODUCTION
The prevalence of obesity and type 2 diabetes has been increasing worldwide, and the use of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide and tirzepatide, has expanded substantially in clinical practice. In this context, growing attention has been directed toward the potential interactions between these metabolic conditions and Helicobacter pylori infection. Although H. pylori is well known for its strong associations with chronic gastritis, peptic ulcer disease, and gastric cancer, recent evidence suggests that the pathogen may also be linked to metabolic processes, including body-weight regulation, glycemic control, and alterations in the gut microbiota [1-3]. In addition, GLP-1 receptor agonists commonly induce upper gastrointestinal symptoms—such as delayed gastric emptying, nausea, and epigastric discomfort—which should be considered important confounding factors when evaluating symptoms potentially attributable to H. pylori infection [4,5]. This review summarizes current evidence published over the past five years, selected from key observational studies, systematic reviews, and expert reviews, regarding how H. pylori infection may influence obesity and diabetes, how metabolic diseases may affect the persistence or prevalence of H. pylori, and how GLP-1 receptor agonists may impact the diagnosis and eradication treatment of H. pylori.
INTERACTIONS BETWEEN H. pylori INFECTION AND OBESITY
Several observational studies have reported that H. pylori infection induces gastric mucosal inflammation, leading to reduced ghrelin secretion and a subsequent decrease in appetite [6]. In addition, increases in circulating ghrelin levels after eradication therapy, along with modest weight gain in some patients, have also been described [7]. Although these findings suggest that H. pylori infection may influence body‐weight regulation, large cohort studies have produced inconsistent results regarding the magnitude and durability of post-eradication weight change. Moreover, multiple confounding factors—including lifestyle, dietary habits, and socioeconomic status—limit the ability to establish a causal relationship between H. pylori infection and obesity [8,9]. Whether obesity increases the risk of H. pylori infection also remains controversial. Some studies have reported a higher prevalence of infection in obese individuals [10], whereas others have found no independent association between obesity and H. pylori [11]. Mechanistic explanations such as alterations in gastric acid secretion, reduced gastric microbial diversity, and obesity-related dysbiosis have been proposed to account for the persistence of infection in obese patients; however, robust supporting evidence is lacking [12,13].
INTERACTIONS BETWEEN H. pylori INFECTION AND TYPE 2 DIABETES
The relationship between H. pylori infection and diabetes has also been examined extensively over several decades. Some studies have reported a higher prevalence of H. pylori infection in patients with type 2 diabetes [14,15], although substantial heterogeneity exists across studies, and factors such as metformin use and glycemic control may confound these associations [14,15]. While certain reports have suggested that H. pylori infection is associated with elevated HbA1c levels [16], a considerable number of investigations have failed to confirm this finding [17]. Although small-scale studies have described modest improvements in HbA1c following eradication therapy [18], the overall evidence remains limited, and randomized controlled trials are lacking, making it difficult to draw definitive conclusions. Proposed biological mechanisms include impaired immune function during hyperglycemia, which could facilitate persistence of infection, as well as infection-induced systemic inflammation that may exacerbate insulin resistance. However, the clinical relevance of these mechanisms remains uncertain, as supporting evidence is still insufficient [19].
IMPLICATIONS OF GLP-1 RECEPTOR AGONISTS FOR H. pylori DIAGNOSIS
With the increasing use of GLP-1 receptor agonists, new considerations have emerged regarding the diagnostic evaluation of H. pylori infection. GLP-1 receptor agonists have been reported to delay gastric emptying and alter fundic relaxation, and may induce gastrointestinal symptoms such as nausea, vomiting, and upper abdominal discomfort [20-22]. Given the characteristics of the urea breath test—whose accuracy can vary depending on intragastric conditions and the test meal— such physiological alterations could theoretically influence test performance [23-25]. Some expert reviews have suggested that adjustments in fasting duration or the timing of medication administration may be considered in patients receiving GLP-1 receptor agonists who undergo endoscopy or other gastrointestinal procedures [26,27]. However, there is currently no evidence demonstrating that GLP-1 receptor agonists have a clinically meaningful impact on the accuracy of H. pylori diagnostic tests such as urea breath test or other modalities such as histology or rapid urease test.
POTENTIAL IMPACT OF GLP-1 RECEPTOR AGONISTS ON H. pylori ERADICATION THERAPY
The evidence that GLP-1 receptor agonists directly influence the success rate of H. pylori eradication therapy remains highly limited. Although delayed gastric emptying may theoretically alter intragastric residence time of antibiotics, there is insufficient evidence to suggest that such changes translate into clinically meaningful differences in eradication efficacy. Common adverse effects of GLP-1 receptor agonists, including nausea and reduced appetite, may reduce adherence to multi-drug eradication regimens and could therefore indirectly influence treatment outcomes.
INFLAMMATION, GUT MICROBIOTA, AND HORMONAL ALTERATIONS IN H. pylori INFECTION
H. pylori infection is associated with increased levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6, which have been implicated in the development of insulin resistance [28]. In addition, infection-related alterations in gastric and intestinal microbial diversity have been reported, with potential links to metabolic disorders [29]. Changes in gastrointestinal hormones, particularly ghrelin and leptin— key regulators of appetite and body weight—have also been described in the context of H. pylori infection and following eradication, suggesting possible interactions between infection status and hormonal regulation [30].
SUMMARY AND FUTURE DIRECTIONS
In summary, although numerous studies have reported associations between H. pylori infection and obesity or type 2 diabetes, a clear causal relationship has not been established. The increasing use of GLP-1 receptor agonists introduces additional considerations in the evaluation of upper gastrointestinal symptoms, diagnostic testing, and adherence to eradication therapy; however, the current evidence supporting these potential interactions remains limited. Furthermore, the possibility of delayed gastric emptying may be considered when interpreting urea breath test results. Future large-scale studies are needed to clarify the mechanistic interactions between H. pylori infection and metabolic disorders and to establish evidence-based diagnostic and therapeutic strategies for patients receiving GLP-1 receptor agonists.
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Availability of Data and Material
Data sharing not applicable to this article as no datasets were generated or analyzed during the study.
Conflicts of Interest
Ju Yup Lee, a contributing editor of the Korean Journal of Helicobacter and Upper Gastrointestinal Research, was not involved in the editorial evaluation or decision to publish this article.
Funding Statement
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Acknowledgements
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