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

  • Ippazio Cosimo Antonazzo
  • Elisabetta Poluzzi
  • Emanuele Forcesi
  • Francesco Salvo
  • Antoine Pariente
  • Giulio Marchesini
  • Fabrizio De Ponti
  • Emanuel RaschiEmail author
Original Article



To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is).


The FDA adverse event reporting system (FAERS) was queried (2004–2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug–drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed).


Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96–1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42–1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62–0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors.


Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.


Myopathy FAERS Drug interactions Antidiabetic drugs 



Authors at the University of Bologna are supported by Institutional funds.

Compliance with ethical standards

Conflict of interest

ICA, EP, EF, FS, AP, FDP and ER have no conflicts of interest relevant to the content of the present work. GM reports personal fees and other from Sanofi, personal fees and other from NOVO Nordisk, personal fees and other from Eli-Lilly, other from Astra Zeneca, other from Glaxo, personal fees and other from Janssen, outside the submitted work.

Ethical approval

For this type of study, ethical approval is not required.

Informed Consent

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

Supplementary material

592_2019_1378_MOESM1_ESM.docx (34 kb)
Supplementary material 1 (DOCX 33 kb)


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Copyright information

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

Authors and Affiliations

  • Ippazio Cosimo Antonazzo
    • 1
  • Elisabetta Poluzzi
    • 1
  • Emanuele Forcesi
    • 1
  • Francesco Salvo
    • 2
    • 3
    • 4
  • Antoine Pariente
    • 2
    • 3
    • 4
  • Giulio Marchesini
    • 5
  • Fabrizio De Ponti
    • 1
  • Emanuel Raschi
    • 1
    Email author
  1. 1.Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater StudiorumUniversity of BolognaBolognaItaly
  2. 2.University of BordeauxBordeauxFrance
  3. 3.INSERM U657BordeauxFrance
  4. 4.CIC Bordeaux CICI1401BordeauxFrance
  5. 5.Unit of Metabolic Diseases and Clinical Dietetics, Department of Medical and Surgical Sciences, Alma Mater StudiorumUniversity of BolognaBolognaItaly

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