(AB) Concomitant Use of Sodium-Glucose Co-Transporter 2 Inhibitors and Statins and The Risk of Myotoxicity - A Pharmacovigilance Study

Publication Number: 673

Background: Recent case reports suggested that sodium-glucose co-transporter 2 (SGLT2) inhibitors may interact with statins via pharmacokinetic mechanisms, thereby increasing the risk of statin-induced myotoxicity. Given the common use of both drug classes in patients with cardiovascular disease and metabolic syndrome, further evidence is needed to understand this potential interaction.

Objectives: To assess the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins.

Methods: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins, or both. The study outcomes were myopathy and rhabdomyolysis, defined using preferred terms from the Medical Dictionary for Regulatory Activities. We assessed several measures of disproportionality for the reporting of the study outcomes associated with concomitant use of SGLT2 inhibitors and statins. We estimated an additive interaction in a linear model (assuming a safety signal when the lower bound of the 95% confidence interval [CI] >0) and a multiplicative interaction using a logistic model to generate reporting odds ratios (RORs) (assuming a safety signal when the lower bound of the 95% CI of the ROR>1). We also computed the Ω shrinkage measure, a method recommended by the WHO for drug-drug interaction (DDI) signal detection (assuming a safety signal when Ω025>0), and the concomitant signal score (CSS), a method that extends the proportional reporting ratio to the DDI setting considering two criteria in the assessment of concomitant signal detection (assuming a safety signal when both CSS criteria are met). In sensitivity analyses, we adjusted for age and sex, and focused on canagliflozin and rosuvastatin, the SGLT2 inhibitor-statin pair with the strongest pharmacological rationale for a DDI.

Results: There were 428 myopathy and 69 rhabdomyolysis reports involving both an SGLT2 inhibitor and a statin in FAERS during the 9-year study period. Concomitant use of SGLT2 inhibitors and statins was not associated with an increased risk of myopathy reporting: coefficient -0.026, 95% CI -0.030 to -0.023; ROR 0.84, 95% CI 0.73 to 0.98; Ω = -0.86; one out of two CSS criteria was met. There was also no increased risk of rhabdomyolysis reporting: coefficient -0.006, 95% CI -0.007 to -0.005; ROR 0.57, 95% CI 0.38 to 0.87; Ω = -1.07; one out of two CSS criteria was met. Adjusting for age and sex and focusing on canagliflozin and rosuvastatin did not alter the results.

Conclusions: Our study showed no increased risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins. The results should provide reassurance regarding the potential interaction between these commonly used drug classes.