Drug–Drug Interaction of the Sodium Glucose Co-Transporter 2 Inhibitors with Statins and Myopathy: A Disproportionality Analysis Using Adverse Events Reporting Data

• Published in: Drug safety Vol. 45; no. 3; pp. 287 - 295
• Main Authors: Alkabbani, Wajd, Pelletier, Ryan, Beazely, Michael A., Labib, Youssef, Quan, Breanna, Gamble, John-Michael
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-03-2022; Springer Nature B.V
• Subjects: Atorvastatin; Case reports; Confidence intervals; Datasets; Diabetes; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Drug dosages; Drug interaction; Drug Interactions; Drug Safety and Pharmacovigilance; Glucose; Glucose transporter; Heart failure; HMG-CoA reductase inhibitors; Humans; Hydroxymethylglutaryl-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hypoglycemic Agents; Hypotheses; Inhibitors; Medicine; Medicine & Public Health; Muscular Diseases - chemically induced; Muscular Diseases - epidemiology; Myopathy; Original Research Article; Patients; Pharmacokinetics; Pharmacology/Toxicology; Reductases; Rhabdomyolysis; Sodium; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Statins; Symporters; United States > US
• ISSN: 0114-5916; 1179-1942
• DOI: 10.1007/s40264-022-01166-3

Introduction
An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports.
Objective
We aimed to assess if the reporting of myopathy is disproportionally higher among people using both SGLT-2i and statins compared to using either SGLT-2i or statins alone.
Methods
We conducted a disproportionality analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We included reports with at least one antihyperglycemic agent. We compared the proportion of myopathy cases to non-cases between those not using SGLT-2i or statins, using SGLT-2i only, statins only, or both. We calculated the reporting odds ratio and 95% confidence interval. We further stratified by individual SGLT-2i and selected statins (rosuvastatin or atorvastatin).
Results
We included 688,388 reports with at least one antihyperglycemic agent recorded, of which 9.80% had at least one SGLT-2i agent. Among all included reports, there were a total of 2202 myopathy cases with the majority, 61.26%, occurring among those using statins alone and only 2.72% of myopathy cases were among those using both SGLT-2i and statins together. Reporting of myopathy was not disproportionally higher among those reporting the use of SGLT-2i with statins (reporting odds ratio 2.95, 95% confidence interval 2.27–3.85) compared to statins alone (reporting odds ratio 6.41, 95% confidence interval 5.86–7.02).
Conclusions
Reports of myopathy were not disproportionally higher among those using SGLT-2i with statins compared to SGLT-2i or statins alone at the class level. Further observational studies may be needed to better assess this interaction at the agent level.