Identifying diabetogenic drugs using real world health care databases: A Danish and Australian symmetry analysis

Lars Christian Lund*, Patricia Hjorslev Jensen, Anton Pottegård, Morten Andersen, Nicole Pratt, Jesper Hallas

*Corresponding author for this work

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Aims: Drug-induced diabetes is underreported in conventional drug safety monitoring and may contribute to the increasing incidence of type 2 diabetes. Therefore, we used routinely collected prescription data to screen all commonly used drugs for diabetogenic effects. Methods: Leveraging the Danish nationwide health registries, we used a case-only symmetry analysis design to evaluate all possible associations between drug initiation and subsequent diabetes. The study was conducted among individuals aged ≥40 years with a first-ever prescription for any antidiabetic drug 1996-2018 (n = 348 996). Sequence ratios (SRs) and 95% confidence intervals (CIs) were obtained for all possible drug class-diabetes combinations. A lower bound of the 95% CI >1.00 was considered a signal. Signals generated in Denmark were replicated using the Services Australia, Pharmaceutical Benefits Scheme 10% data extract. Results: Overall, 386 drug classes were investigated, of which 70 generated a signal. In total, 43 were classified as previously known based on the SIDER database or a literature review, for example, glucocorticoids (SR 1.67, 95% CI 1.62-1.72) and β-blockers (SR 1.20, 95% CI 1.16-1.23). Of 27 new signals, three drug classes yielded a signal in both the Danish and Australian data source: digitalis glycosides (SR 2.15, 95% CI 2.04-2.27, and SR 1.76, 95% CI 1.50-2.08), macrolides (SR 1.20, 95% CI 1.16-1.24, and SR 1.11, 95% CI 1.06-1.16) and inhaled β2-agonists combined with glucocorticoids (SR 1.35, 95% CI 1.28-1.42, and SR 1.14, 95% CI 1.06-1.22). Conclusion: We identified 70 drug-diabetes associations, of which 27 were classified as hitherto unknown. Further studies evaluating the hypotheses generated by this work are needed, particularly for the signal for digitalis glycosides.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Issue number5
Pages (from-to)1311-1320
Publication statusPublished - May 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.


  • adverse drug reactions
  • diabetes mellitus
  • pharmacoepidemiology
  • Denmark/epidemiology
  • Diabetes Mellitus, Type 2/drug therapy
  • Glucocorticoids
  • Global Health
  • Humans
  • Australia/epidemiology
  • Hypoglycemic Agents/adverse effects


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