CEN Case Reports

, Volume 7, Issue 1, pp 29–33 | Cite as

Development of hyperkalemia following treatment with dapagliflozin (DAPA) in a patient with type 2 diabetes after bilateral adrenalectomy

  • Daichi Miyaoka
  • Akihiro Tsuda
  • Noriyuki Hayashi
  • Norikazu Toi
  • Akiyo Yamasaki
  • Yuki Nagata
  • Shinya Nakatani
  • Masafumi Kurajoh
  • Shinsuke Yamada
  • Tomoaki Morioka
  • Yasuo Imanishi
  • Masanori Emoto
  • Masaaki Inaba
Case Report

Abstract

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.

Keywords

Dapagliflozin Type 2 diabetes Hyperkalemia Aldosterone deficiency Renin–angiotensin–aldosterone system 

Notes

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

Informed consent was obtained from the patient for the publication of this case report.

References

  1. 1.
    Ferrannini E, et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33:2217–24.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Imprialos KP, et al. Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease: a valuable effect of a novel antidiabetic class? J Hypertens. 2015;33:2185–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Heerspink HL, et al. Composite renal endpoints: was ACCOMPLISH accomplished? The Lancet. 2010;375:1140–2.CrossRefGoogle Scholar
  4. 4.
    Weir MR, et al. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014;30:1759–68.CrossRefPubMedGoogle Scholar
  5. 5.
    Ernst ME, et al. Use of diuretics in patients with hypertension. N Engl J Med. 2010;361:2153–64.CrossRefGoogle Scholar
  6. 6.
    Cherney DZ, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129:587–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Lambers Heerspink HJ, et al. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15:853–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Zacchia M, et al. Potassium: from physiology to clinical implications. Kidney Dis (Basel). 2016;2:72–9.CrossRefGoogle Scholar
  9. 9.
    Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351:585–92.CrossRefPubMedGoogle Scholar
  10. 10.
    Yavin Y, et al. Effect of the SGLT2 inhibitor dapagliflozin on potassium levels in patients with type 2 diabetes mellitus: a pooled analysis. Diabetes Ther. 2016;7:125–37.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Vivian EM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of antidiabetic agents. Drugs Context. 2014;3:212264.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fioretto P, et al. SGLT2 inhibitors and the diabetic kidney. Diabetes Care. 2016;39(Suppl 2):S165-171.Google Scholar
  13. 13.
    Kohan DE, et al. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85:962–71.CrossRefPubMedGoogle Scholar
  14. 14.
    Wanner C, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2017

Authors and Affiliations

  • Daichi Miyaoka
    • 1
  • Akihiro Tsuda
    • 1
  • Noriyuki Hayashi
    • 1
  • Norikazu Toi
    • 1
  • Akiyo Yamasaki
    • 1
  • Yuki Nagata
    • 1
  • Shinya Nakatani
    • 1
  • Masafumi Kurajoh
    • 1
  • Shinsuke Yamada
    • 1
  • Tomoaki Morioka
    • 1
  • Yasuo Imanishi
    • 1
  • Masanori Emoto
    • 1
  • Masaaki Inaba
    • 1
  1. 1.Department of Metabolism, Endocrinology and Molecular Medicine, Internal MedicineOsaka City University Graduate School of MedicineOsakaJapan

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