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

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Abstract

Aims

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.

Methods

We searched the PubMed, MEDLINE, Embase, Cochrane and ClinicalTrials.gov 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.

Results

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.

Conclusions

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.

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Abbreviations

CCB:

Calcium channel blocker

FPG:

Fasting plasma glucose

HbA1c:

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

Rob:

Risk of bias

T2D:

Type 2 diabetes

TXNIP:

Thioredoxin-interacting protein

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Acknowledgements

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

Funding

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.

Author information

Authors and Affiliations

  1. Unit Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, “Luigi Sacco” University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy

    Carla Carnovale, Giulia Mosini, Faizan Mazhar, Sonia Radice & Emilio Clementi

  2. International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy

    Alice Dassano, Francesca D’Addio & Paolo Fiorina

  3. Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy

    Marco Pozzi & Emilio Clementi

  4. Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Paolo Fiorina

  5. Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157, Milan, Italy

    Paolo Fiorina

Authors
  1. Carla Carnovale
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  2. Alice Dassano
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  3. Giulia Mosini
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  4. Faizan Mazhar
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  5. Francesca D’Addio
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  6. Marco Pozzi
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  7. Sonia Radice
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  8. Paolo Fiorina
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  9. Emilio Clementi
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Contributions

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.

Corresponding author

Correspondence to Carla Carnovale.

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Supplementary Figure 1

Summary of the risk-of-bias assessment, according to the Cochrane Collaboration tool. (TIFF 259 kb)

Supplementary material 2 (DOC 64 kb)

Supplementary material 3 (DOCX 132 kb)

Supplementary material 4 (DOCX 63 kb)

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Carnovale, C., Dassano, A., Mosini, G. et al. The β-cell effect of verapamil-based treatment in patients with type 2 diabetes: a systematic review. Acta Diabetol 57, 117–131 (2020). https://doi.org/10.1007/s00592-019-01370-1

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  • DOI: https://doi.org/10.1007/s00592-019-01370-1

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