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Risk of cancer in patients treated with dipeptidyl peptidase-4 inhibitors: an extensive meta-analysis of randomized controlled trials

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Abstract

Aims

Observational studies and meta-analyses of randomized trials on dipeptidyl peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of malignancies with this class of drugs. Aim of the present meta-analysis is the assessment of the effect of DPP4i treatment on the incidence of different types of cancer, collecting all available evidence from randomized controlled trials.

Methods

An extensive MEDLINE, EMBASE, and Cochrane database search for sitagliptin or vildagliptin or omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥ 24 weeks, and comparing of DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel–Haenszel odds ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes.

Results

A total of 157 eligible trials were identified. DPP-4i were not associated with an increased risk of overall cancer (MH-OR 0.93 [0.86, 1.00]; p = 0.07), with no significant differences across individual molecules of the class. When compared with placebo/none, a lower risk of cancer with DPP-4i was observed in placebo-controlled trials (MH-OR 0.90 [0.82, 0.99], p = 0.030), whereas no significant differences have been detected with any other comparators. DPP-4i was associated with a significant reduction in colorectal cancer (MH-OR 0.70 [0.53, 0.94], p = 0.020).

Conclusions

Available data do not support the hypothesis of an association of DPP4i treatment with malignancies, with a possible beneficial effect for colon-rectal cancer.

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Funding

This research was performed as a part of the institutional activity of the unit, with no specific funding. All expenses, including salaries of the investigators, were covered by public research funds assigned to the unit. The manuscript was drafted and revised by the authors in accordance with ICJME standards for authorship. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Author notes

  1. Ilaria Dicembrini and Besmir Nreu have contributed equally to this work.

Authors and Affiliations

  1. Diabetology, Careggi Hospital and University of Florence, Via delle Oblate 4, 50141, Florence, Italy

    Ilaria Dicembrini, Besmir Nreu, Chiara Montereggi, Edoardo Mannucci & Matteo Monami

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  1. Ilaria Dicembrini
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  2. Besmir Nreu
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  3. Chiara Montereggi
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  4. Edoardo Mannucci
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  5. Matteo Monami
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Contributions

MM and EM were involved in design, data collection, analysis, and writing manuscript. ID, BN, and CM were involved in data collection and manuscript revision.

Corresponding author

Correspondence to Matteo Monami.

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Conflict of interest

ID has received speaking fees from Novonordisk; CM has no conflict of interest; BN is presently employee of Novo Nordisk; FT has no conflicts of interest to declare MM has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Bristol Myers Squibb; EM has received consultancy fees from Merck and Novartis speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Merck, Novartis, and Takeda. All the authors approved the final version of this manuscript. Dr. Matteo Monami is the person who takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

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Dicembrini, I., Nreu, B., Montereggi, C. et al. Risk of cancer in patients treated with dipeptidyl peptidase-4 inhibitors: an extensive meta-analysis of randomized controlled trials. Acta Diabetol 57, 689–696 (2020). https://doi.org/10.1007/s00592-020-01479-8

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