The β-cell effect of verapamil-based treatment in patients with type 2 diabetes: a systematic review

  • Carla CarnovaleEmail author
  • Alice Dassano
  • Giulia Mosini
  • Faizan Mazhar
  • Francesca D’Addio
  • Marco Pozzi
  • Sonia Radice
  • Paolo Fiorina
  • Emilio Clementi
Review Article



The possibility that verapamil has new beneficial effects in diabetic patients in terms of an improvement in glycometabolic control has been put forward recently in several studies. However, to date the issue is still under debate. We conducted the first systematic review examining the impact of verapamil-based treatment on glycometabolic outcomes, in type 2 diabetes (T2D) patients.


We searched the PubMed, MEDLINE, Embase, Cochrane and up to 9 October 2018, for all studies evaluating whether verapamil-based treatment is associated with changes in glycated haemoglobin (HbA1c), fasting plasma glucose levels, glucose and C-peptide areas from baseline in humans, without restrictions for study type.


Plasma glucose levels were lowered significantly by verapamil-based treatment in patients with T2D (mean change − 13 ± 5.29; P = 0.049); HbA1c values were instead not affected by the drug (mean change − 0.10 ± 0.12; P = 0.453). In five studies, groups exposed to verapamil achieved lower value of glycometabolic outcomes: comparison with values recorded in control groups showed a significant difference, in terms of both HbA1c and plasma glucose levels.


Despite the fact that plasma glucose levels were lowered significantly by verapamil-based treatment in patients with T2D (the HbA1c values were not affected by the drug), the clinical significance of the glycometabolic response induced by verapamil-based treatment remains unclear due to the high variety of sample size and type of studies presently available. Further experimental and clinical trials are needed to clarify unambiguously the role of verapamil in metabolic control.


Glycometabolic control HbA1c FPG Diabetes Calcium channel blockers Verapamil 



Calcium channel blocker


Fasting plasma glucose


Haemoglobin A1c, A1C, glycosylated haemoglobin, glycated haemoglobin, glycol-haemoglobin


Risk of bias


Type 2 diabetes


Thioredoxin-interacting protein



Faizan Mazhar is supported by the 33rd cycle Ph.D. programme in “Scienze Farmacologiche Sperimentali e Cliniche”, Università degli Studi di Milano.

Author contribution

CC conceptualised and designed the study, carried out the data extraction and statistical analyses, drafted the manuscript and the summary tables, revised and approved the final manuscript as submitted; AD, GM and FM contributed to literature extraction and manuscript revision and approved the final manuscript as submitted; FD, MP and SR participated in the conceptualisation and design of the study, participated in the analysis of the data, revised the article, and approved the final article as submitted. PF and EC contributed to concept and design of the study, participated in the analysis and interpretation of the data, coordinated and supervised data collection, critically reviewed the manuscript and approved the final manuscript as submitted.


The financial support by the Agenzia Italiana del Farmaco (AIFA), by the Centre of Pharmacovigilance of Regione Lombardia (MEAP project, Monitoraggio degli Eventi Avversi nelle Popolazioni a Rischio, to EC), by the Italian Ministry of Health (Ricerca Corrente 2018, to MP) is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

592_2019_1370_MOESM1_ESM.tif (259 kb)
Supplementary Figure 1 Summary of the risk-of-bias assessment, according to the Cochrane Collaboration tool. (TIFF 259 kb)
592_2019_1370_MOESM2_ESM.doc (64 kb)
Supplementary material 2 (DOC 64 kb)
592_2019_1370_MOESM3_ESM.docx (132 kb)
Supplementary material 3 (DOCX 132 kb)
592_2019_1370_MOESM4_ESM.docx (64 kb)
Supplementary material 4 (DOCX 63 kb)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmacovigilance Service, Unit Clinical Pharmacology, Department of Biomedical and Clinical SciencesUniversity Hospital “Luigi Sacco”- University of Milan ASST Fatebenefratelli-SaccoMilanItaly
  2. 2.International Center for T1D, Pediatric Clinical Research Center, Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences L. Sacco“Luigi Sacco” University Hospital, Università di MilanoMilanItaly
  3. 3.Scientific Institute IRCCS Eugenio MedeaBosisio PariniItaly
  4. 4.Biomedical and Clinical Science L. SaccoUniversità di MilanoMilanItaly
  5. 5.Nephrology DivisionBoston Children’s Hospital, Harvard Medical SchoolBostonUSA
  6. 6.Division of EndocrinologyASST Fatebenefratelli-SaccoMilanItaly

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