Glucose-Regulating Effects of H1 Antihistamines: A Comprehensive Systematic Review of Clinical and Preclinical Evidence

Histamine H1-receptor antagonists (H1 antihistamines) are widely used for allergic disorders, and studies have reported mixed effects of these drugs on glucose-related outcomes. This systematic review summarised the glucose-regulating effects reported for H1 antihistamines in human, animal and relevant experimental studies. PubMed was searched on 9 October 2026 (614 records) without filters, and Google Scholar was searched as a supplementary source. After removal of duplicates and unrelated or non-original records, 94 records were screened by title and abstract, and 20 studies were included: six human studies, nine animal studies and five biochemical, cellular or mechanistic studies. Risk of bias was assessed with RoB 2, ROBINS-I and the SYRCLE tool according to study design. Heterogeneity and missing data precluded meta-analysis, so a narrative synthesis was used. In humans, one short study reported higher post-load glucose with cetirizine, a small historical study reported lower fasting glucose with terfenadine, and add-on trials in diabetic kidney disease reported mainly renal benefits, with an HbA1c difference in one levocetirizine trial. Animal studies reported improved glucose tolerance or insulin resistance with cetirizine, levocetirizine and ketotifen in some models, higher fasting glucose with desloratadine, and no clear glucose lowering with bilastine. Fexofenadine inhibited recombinant human DPP-4 in an earlier assay (IC50 4.6 ± 1.0 μM). The available literature does not establish H1 antihistamines as a uniform class of glucose-regulating agents, and improvements in renal or inflammatory markers should not be read as direct glycaemic benefit. Well-designed clinical studies with clearly defined glycaemic outcomes are needed