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Published in: Acta Diabetologica 1/2020

01-01-2020 | Diseases of the neuromuscular synapses and muscles | Letter to the Editor

A missed protective drug–drug interaction of DPP-4 inhibitors and statins on myopathy risk

Authors: Oliver Kuss, Wolfgang Rathmann

Published in: Acta Diabetologica | Issue 1/2020

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Excerpt

With great interest, we read the recent paper of Antonazzo et al. [1] on the risk of myopathy related to DPP-4 inhibitors and statin use. Antonazzo et al. used 142,888 myopathy cases and 858,627 non-cases from FAERS, the FDA adverse event reporting system [1]. The authors were especially interested in potential interactions between the two drugs and therefore refer to and use the approach of Thakrar et al. [2] which entails a multiplicative and an additive model to assess drug interactions. Antonazzo et al. computed both models, but did not give confidence intervals for the estimated interaction terms. When using the raw data from Table 2 of Antonazzo et al. and the GENMOD procedure in SAS (SAS Institute Inc., Cary, NC, USA, see Appendix for the code), as recommended by Thakrar et al., we observed statistically significant and clinically relevant negative interactions from the multiplicative as well as from the additive model (Table 1). Therefore, we disagree with the conclusion of Antonazzo et al., that a “drug interaction is very unlikely.”
Table 1
Results from fitting the additive and the multiplicative model of Thakrar et al. [2] to the data set for DPP-4 inhibitors and statins on the risk of myopathy, as given in Table 2 of Antonazzo et al. [1]
Parameter
Estimate
95% CI
p value
Additive model
DPP4
0.017
[0.013; 0.020]
< 0.0001
Statin
0.121
[0.120; 0.123]
< 0.0001
Interaction
− 0.033
[− 0.040; − 0.026]
< 0.0001
Multiplicative model
Exp (DPP4)
1.173
[1.140; 1.207]
< 0.0001
Exp (Statin)
2.265
[2.238; 2.292]
< 0.0001
Exp (Interaction)
0.789
[0.757; 0.824]
< 0.0001
Appendix
Available only for authorised users
Literature
1.
go back to reference Antonazzo IC, Poluzzi E, Forcesi E, Salvo F, Pariente A, Marchesini G, De Ponti F, Raschi E (2019) Myopathy with DPP-4 inhibitors and statins in the real world: investigating the likelihood of drug-drug interactions through the FDA adverse event reporting system. Acta Diabetol. https://doi.org/10.1007/s00592-019-01378-7 CrossRef Antonazzo IC, Poluzzi E, Forcesi E, Salvo F, Pariente A, Marchesini G, De Ponti F, Raschi E (2019) Myopathy with DPP-4 inhibitors and statins in the real world: investigating the likelihood of drug-drug interactions through the FDA adverse event reporting system. Acta Diabetol. https://​doi.​org/​10.​1007/​s00592-019-01378-7 CrossRef
2.
go back to reference Thakrar BT, Grundschober SB, Doessegger L (2007) Detecting signals of drug-drug interactions in a spontaneous reports database. Br J Clin Pharmacol 64:489–495CrossRef Thakrar BT, Grundschober SB, Doessegger L (2007) Detecting signals of drug-drug interactions in a spontaneous reports database. Br J Clin Pharmacol 64:489–495CrossRef
3.
go back to reference Ihle P, Dippel FW, Schubert I (2018) Statin-associated myopathy. Assessment of frequency based on data of all statutory health insurance funds in Germany. Pharmacol Res Perspect 6(3):e00404CrossRef Ihle P, Dippel FW, Schubert I (2018) Statin-associated myopathy. Assessment of frequency based on data of all statutory health insurance funds in Germany. Pharmacol Res Perspect 6(3):e00404CrossRef
Metadata
Title
A missed protective drug–drug interaction of DPP-4 inhibitors and statins on myopathy risk
Authors
Oliver Kuss
Wolfgang Rathmann
Publication date
01-01-2020
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 1/2020
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-019-01440-4

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