ArticleDiabetology & metabolic syndrome2025
Protective effect of antidiabetic drugs against male infertility: evidence from Mendelian randomization.
Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic Evidence for the Benefits and Risks of Glucose-Lowering Drugs on Cardiovascular-Kidney-Metabolic Syndrome: A Drug-Target Mendelian Randomization Study.International journal of medical sciences · 2026 · on this mapPooled it
- Cadmium chloride and erectile dysfunction: integrative evidence from network toxicology, Mendelian randomization, andFrontiers in endocrinology · 2026Article
- Exploring the role of febuxostat's drug target XOR in erectile dysfunction: insights from human genetics and rat models.Frontiers in medicine · 2025Article
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7 authors.
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Abstract
backgroundThe global prevalence of diabetes has been steadily increasing, with a growing number of younger individuals being affected. Over recent decades, various antidiabetic drugs have been repurposed for treating conditions beyond diabetes. However, the effects of antidiabetic drugs on male infertility (MIF) remain inadequately elucidated. This Mendelian randomization (MR) study aims to clarify the potential impact of antidiabetic drugs on the risk of MIF.
methodWe designed a comprehensive analytical workflow involving two-sample MR and summary-based MR (SMR) to assess the causal relationship between antidiabetic drug targets and MIF. First, instrumental variables were obtained based on HbA1c levels and gene expression levels. Then, MR analysis was performed after selecting positive target genes from four blood glucose level and type 2 diabetes (T2DM) datasets. Finally, we applied SMR analysis to validate and expand upon the previous conclusions. Additionally, sensitivity analyses were conducted to evaluate the robustness of the results.
resultsSeven drug targets associated with five antidiabetic drugs were identified as significantly related to MIF. In the two-sample MR, the following drugs were found to reduce MIF risk through their respective significant targets: metformin (GPD1: IVW OR 0.007, 95% CI 0.000-0.204, P = 0.004), SGLT2 inhibitors (SGLT2i) (SLC5A1: IVW OR 0.048, 95% CI 0.004-0.585, P = 0.017), insulin and its analogs (IGF1R: IVW OR 0.773, 95% CI 0.648-0.922, P = 0.004), and sulfonylureas (TRPM4: IVW OR 0.869, 95% CI 0.766-0.985, P = 0.028; CTPA1: IVW OR 0.838, 95% CI 0.741-0.947, P = 0.005). In SMR analysis, antidiabetic drugs targeting the genes CPE (P = 0.03, HEIDI = 0.970) and TRPM4 (P = 0.028, HEIDI = 0.746) were found to significantly reduce the risk of MIF.
conclusionOur study indicates that metformin, SGLT2i, insulin and its analogs, as well as sulfonylureas, may offer potential therapeutic benefits for MIF. Specifically, six antidiabetic drug target genes GPD1, SLC5A1, IGF1R, TRPM4, CPT1 A, and CPE may play a role in the progression of MIF. These findings have significant implications for the development of personalized precision therapies for MIF.
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