ArticleDiabetologia2025
Verapamil and low-dose anti-mouse thymocyte globulin combination therapy stably reverses recent-onset type 1 diabetes in NOD mice by acting on the beta cell and immune axes.
Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Impact of Body Size on Preclinical Type 1 Diabetes Development and Progression.Diabetes care · 2026Review
- GLP1-E2 therapy delays autoimmune diabetes in late-stage prediabetic NOD mice and potentiates low-dose anti-CD3 therapy for enhanced disease protection.Diabetologia · 2026Article
- Review
- Redosing of anti-CD3 antibodies in NOD mice with new-onset diabetes does not alter the effect of a single treatment course.Diabetologia · 2026Article
- Article
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Authors and funding
10 authors.
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Abstract
aims/hypothesisVerapamil, a calcium channel blocker, and low doses of anti-thymocyte globulin (ATG) have individually shown efficacy in preserving beta cell function in people with recent-onset symptomatic type 1 diabetes (stage 3). We hypothesised that combining interventions with complementary modes of action and different targets would increase their efficacy in arresting beta cell demise and promoting disease recovery.
methodsContinuous administration of verapamil via drinking water, combined with a short course of low-dose rabbit-anti-mouse ATG (mATG), was studied in female recent-onset diabetic NOD mice for its potential to induce disease remission and mechanism of action.
resultsVerapamil stably reversed diabetes in 3 out of 15 mice (20%) by day 56 after therapy start. Low-dose mATG reversed diabetes in 7 out of 18 mice (39%) by day 7 after therapy start, yet the effect waned to 3 out of 18 mice (17%) by day 56. The combination of verapamil with mATG induced durable diabetes reversal in 9 out of 20 mice (45%) by day 56, which was associated with preserved beta cell function, higher pancreatic insulin content and increased total beta cell volume with decreased severe insulitis. mATG, both alone and in combination, induced a temporary depletion of lymphocytes in peripheral blood on day 3 after therapy start, which largely recovered by day 14, when naive cells had shifted to a memory phenotype in both CD4 CONCLUSIONS/
interpretationThe combination of verapamil and low-dose mATG outperformed monotherapy in reversing recent-onset type 1 diabetes in NOD mice. This approach targets both the beta cell and immune axes, suggesting a promising strategy for disease reversal in human type 1 diabetes.
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