Endocrine Abstracts

Introduction: Sodium/glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycemic agents that are increasingly used in the management of type 2 diabetes mellitus (T2DM). They are now recommended as second-line pharmacotherapy (in conjunction with metformin) in patients with type 2 diabetes and established atherosclerotic heart disease, heart failure or chronic kidney disease due to their favourable effects on cardiovascular and renal outcomes. We report a case of a 47-year-old woman who developed rhabdomyolysis after commencing the SGLT2 inhibitor empagliflozin. Case presentation: A 47-year-old female case was followed in the endocrinology clinic for T2DM, hyperlipidemia and chronic renal failure (Cre:1.73 mg/dl, GFR:35 ml/min and spot urine albumin/creatinine ratio:243 mg/g). She had been using linagliptin, insulin detemir, fenofibrate, rosuvastatin, candesartan and acetylsalicylic acid for two years. Empaglifozin was added because of her high HbA1c level (7.8%) and renal dysfunction. The patient presented to the emergency department with the complaint of muscle pain two weeks after starting empaglifozin. Laboratory results showed elevated creatinine kinase (CK) level of 3014 U/l (reference range 0-150 U/l) and increased creatinine level (2.84 mg/dl). Her CK levels were in normal range before empagliflozin treatment. No elevation in troponin levels was observed during follow-up. The patient was hospitalized with a diagnosis of rhabdomyolysis. Intravenous saline infusion therapy was started. Rosuvastatin, fenofibrate and empaglifozin were stopped. During the follow-up, creatinine kinase levels decreased to normal levels and creatinine level regressed to its basal level within a week.

Conclusion: Drug-induced myopathies may present with varying severity, ranging from asymptomatic CK elevation, myalgia to rhabdomyolysis with acute kidney injury. Commonly implicated agents are statins and glucocorticoids. There are few case reports in the literature reporting development of myopathy after empaglifozin treatment with/without statins. On the otherhand, a retrospective study including 2202 cases of myopathy by Alkabbani et al., found that reports of myopathy were not disproportionally higher among those using SGLT-2 inhibitors with statins compared to SGLT-2 inhibitors or statins alone at the class level. Although our patient was using rosuvastatin and fenofibrate which are well-described causes of drug-induced rhabdomyolysis, we thought that empaglifozin might induce rhabdomyolysis because of long-term use of anti-hyperlipidemic drugs and the development of rhabdomyolysis 2 weeks after starting empaglifozin. Since the pathogenesis is not known, further studies are needed to determine the relationship between SGLT2 inhibitors and drug-induced myopathy and clinicians should keep in mind the risk of rhabdomyolysis with increased utilization of these drugs.