Antidiabetic Properties of Histamine H1 Receptor Antagonists: A Systematic Review

Allergies and diabetes mellitus are highly prevalent, frequently co-occurring diseases. Antihistamines, the first-line treatment for allergies, block H1 receptors but also exhibit anti-inflammatory and antioxidant properties that may improve glucose metabolism. This systematic review examined the evidence for the potential antidiabetic effects of commonly used first- and second-generation antihistamines. A comprehensive search of the PubMed database (1978-May 2026) yielded 17 eligible in vivo, in vitro, clinical, and in silico studies. Most reports indicated that antihistamines improve glucose tolerance, insulin sensitivity, and insulin secretion. Proposed mechanisms include enhanced insulin release, mast cell stabilization, attenuation of immune-mediated responses, reduced nephron alteration, and improved incretin signalling. Although substantial heterogeneity in study designs limits direct comparisons, current evidence suggests a beneficial role of antihistamines in modulating glucose metabolism, particularly for patients managing both allergies and diabetes. These findings highlight the potential for drug repurposing. However, further well-designed clinical trials are required to ensure reproducibility, successful animal-to-human translation, and overall safety before clinical implementation.