Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus
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Laboratory Animal Science Group, IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
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Instituto de Investigação e Inovação da Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
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Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, Kassai út 26, 4028 Debrecen, Hungary
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Faculty of Public Health, University of Debrecen, Kassai út 26, 4028 Debrecen, Hungary
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Faculty of Medicine, University of Debrecen, Egyetem Square 1, 4032 Debrecen, Hungary
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Institute of Pharmacology and Experimental Therapeutics, and Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
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Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal
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Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal
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Office for Research Groups Attached to Universities and Other Institutions, Hungarian Academy of Sciences, 1051 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Dario Brunetti
Biology 2021, 10(2), 155; https://doi.org/10.3390/biology10020155
Received: 14 January 2021
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Revised: 10 February 2021
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Accepted: 13 February 2021
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Published: 16 February 2021
(This article belongs to the Special Issue Preclinical Models in Translational Medicine)
Simple Summary
The value of animal models to predict human outcomes has been increasingly challenged due to a low rate of translation between preclinical and clinical trials. However, translational failure has been proposed to be at least partly explained by the poor methodological quality of animal studies. We thus retrospectively assessed the predictive value of animal models in Type-2-diabetes research, comparing the same outcome measure (glycaemia) in response to a currently available class of antidiabetic drugs between published clinical trials and animal studies, and assessed methodological quality of the latter. In our sample, both mice and rats performed similarly to humans in response to dipeptidyl peptidase-4 (DPP4) inhibitors. These results, while on animal models of just one disease treated with one drug class, suggest current criticism of animal models may not be entirely warranted, though we found a margin for improvement in the research quality of animal studies.
Although there is a wide range of animal models of type 2 diabetes mellitus (T2DM) used in research; we have limited evidence on their translation value. This paper provides a) a comparison of preclinical animal and clinical results on the effect of five dipeptidyl peptidase-4 (DPP4) inhibitors by comparing the pharmaceutical caused glucose changes, and b) an evaluation of methodological and reporting standards in T2DM preclinical animal studies. DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin. In our analysis of 124 preclinical studies and 47 clinical trials, (1) we found no evidence of species differences in glucose change response to DPP4 inhibitors, which may suggest that, for this drug class, studies in mice and rats may be equally predictive of how well a drug will work in humans; and (2) there is good reporting of group size, sex, age, euthanasia method and self-reported compliance with animal welfare regulations in animal studies but poor reporting of justification of group size, along with a strong bias towards the use of male animals and young animals. Instead of the common non-transparent model selection, we call for a reflective and evidenced-based assessment of predictive validity of the animal models currently available.
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Keywords:
animal models; predictive validity; type 2 diabetes mellitus; translational medicine; research bias
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MDPI and ACS Style
Franco, N.H.; Miranda, S.B.; Kovács, N.; Nagy, A.; Thiện, B.Q.; Reis, F.; Varga, O. Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus. Biology 2021, 10, 155. https://doi.org/10.3390/biology10020155
AMA Style
Franco NH, Miranda SB, Kovács N, Nagy A, Thiện BQ, Reis F, Varga O. Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus. Biology. 2021; 10(2):155. https://doi.org/10.3390/biology10020155
Chicago/Turabian StyleFranco, Nuno H., Sonia B. Miranda, Nóra Kovács, Attila Nagy, Bùi Q. Thiện, Flávio Reis, and Orsolya Varga. 2021. "Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus" Biology 10, no. 2: 155. https://doi.org/10.3390/biology10020155
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