Development of Hyperkalemia Following Treatment with Dapagliflozin (DAPA) in a Patient with Type 2 Diabetes After Bilateral Adrenalectomy

Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is known to have a beneficial diuretic effect, in addition to a glucose-lowering effect. Although SGLT2 inhibitor has been reported, the increase of hyperkalemia in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors, their mechanism of action is unclear. We report the first case of a type 2 diabetes (T2DM) patient with potential mineralocorticoid deficiency who developed hyperkalemia after administration of DAPA. A 79-year-old woman underwent bilateral adrenalectomy for uncontrolled hypercortisolism due to an inoperable recurrence of Cushing's disease, and she was subsequently maintained on replacement therapy with glucocorticoid. She was diagnosed as having T2DM at 71 years of age and was treated with sitagliptin and miglitol. Since she presented with weight gain of about 5 kg over 6 months and her HbAlc level increased over 12%, 5 mg/day DAPA was added to her daily regimen. After the start of DAPA treatment, she developed hyperkalemia (6.5 mEq/L) with increased plasma renin activity of 53.1 ng/mL/h. She was diagnosed with aldosterone deficiency and started on fludrocortisone 0.1 mg daily, after which the hyperkalemia improved immediately. In this case, DAPA treatment could potentially increase the requirement for mineralocorticoid replacement, directly suggesting that the SGLT2 inhibition-induced natriuretic effect is accompanied by compensatory activation of the RAAS axis, which is essential to keep the serum potassium level within the normal range. Therefore, physicians should be careful about the development of hyperkalemia in patients when SGLT2 and RAAS inhibitors are used in combination.