Sodium-Glucose Co-Transporter Protein 2 Inhibitors Induced Hypercalcemia: A Case Series and Literature Review

BACKGROUND: Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents. To our knowledge, hypercalcemia has not been labeled as a side effect of this class; nevertheless, 2 cases have been reported over the last few years. CASE REPORT: We present a case series of 3 patients with type 2 diabetes mellitus (T2DM) in whom hypercalcemia developed when they were started on canagliflozin and dapagliflozin treatment. In cases 1 and 2, hypercalcemia developed shortly after increasing the canagliflozin dose. In both cases, calcium levels returned to the normal range 1 week after discontinuing canagliflozin treatment. In case 3, laboratory workup revealed an elevated serum calcium level shortly after switching the therapy to dapagliflozin. DISCUSSION: The first reported case of hypercalcemia related to SGLT2 inhibitor use was described in relation to canagliflozin. High calcium level was also reported in a patient after introducing dapagliflozin. In our cases, hypercalcemia was first noted after increasing the dose of canagliflozin and after introducing dapagliflozin. Although the exact causes are unknown, we propose a comprehensive multifactorial mechanism. CONCLUSION: This is the first reported case series of hypercalcemia associated with SGLT2 inhibitors. Although the exact mechanisms remain uncertain, these drugs may predispose individuals to hypercalcemia. Monitoring for signs and symptoms of hypercalcemia or better switching to more selective SGLT2 inhibitors in at-risk patients could potentially prevent this complication.