SGLT2 inhibitor associated diabetic ketoacidosis

Empagliflozin is a representative of SGLT2 inhibitors, which is used for the treatment of type 2 diabetes mellitus. Common adverse reactions are hypoglycemia and urinary tract infections. We reported a case of 76-year-old female, receiving empagliflozin and being admitted to the hospital because of diabetic ketoacidosis. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 8 No. 4, April 2017. ISSN – [0976-3198] Int J Case Rep Images 2017;8(4):239–241. www.ijcasereportsandimages.com Mitsiou et al. 239 CASE REPORT PEER REVIEWED | OPEN ACCESS SGLT2 inhibitor associated diabetic ketoacidosis Evdoxia Mitsiou, Charalampos Mandros, Kalliopi Kotsa, Frangiskos Koulis, Charalampos Christofidis, Sofia Georgiadi, Theodolinta Testa, Alexandros Anastasiou, Evgenia Efthymiou, Evangelos Potolidis


INTRODUCTION
SGLT2 inhibitors are sodium-glucose cotransporter 2 inhibitors (SGLT2) in the proximal renal tubules that reduce reabsorption of filtered glucose from the tubular lumen and lower the renal threshold for glucose (RTG). Therefore, SGLT2 is the main site of filtered glucose reabsorption. By inhibiting SGLT2, urine glucose excretion increases and plasma glucose concentration reduces [1]. The SGLT2 inhibitors are generally weak glucose-lowering agents, similar to efficacy to the DPP-4 inhibitors. Empagliflozin is one of the representatives of this category of glucose-lowering agents, which is used for the treatment of type 2 diabetes mellitus, usually in combination with metformin [2] or insulin [3], as an adjunct to exercise and diet to improve glycemic control. Common adverse reactions are hypoglycemia and urinary tract infections [4]. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs may increase the risk of diabetic ketoacidosis [5]. Moreover, in May 2015, the Food and Drug Association issued a warning that SGLT2 inhibitors can increase the incidence of diabetic ketoacidosis [6]. It also identified potential triggering factors such as illness, reduced food and fluid intake, reduced insulin doses, and history of alcohol intake. Our case will be one of the few cases of diabetic ketoacidosis reported in a patient with type 2 diabetes mellitus [7].

CASE REPORT
A 76-year-old female was admitted to our hospital because of increased fatigue and weakness during the last 10 days. At the same time, she started receiving medication for type 2 diabetes mellitus, which concluded metformin 850 (1x1) and empagliflozin 10 (1x1). She did not receive any other medication. She reported just one fever wave up to 38ºC, three days before the admission.
The patient was treated as having diabetic ketoacidosis due to type 1 diabetes mellitus. She aggressively received intravenous fluids and insulin and she was covered empirically with a broad spectrum antibiotic because of elevated CRP, even though she did not have any fever during her hospitalization. Urinalysis continued to show elevated glucose levels and ketones, until the day of discharge, on day-8. Blood gas tests stopped to show acidosis on the third day, but the base deficit remained high until the seventh day (HCO 3 16.9 mmol/l, base excess 9.0 mmol/l). The test was normal on the day of discharge.

DISCUSSION
Empagliflozin is an SGLT2 inhibitor usually used in combination with metformin or insulin in order to further reduce serum glucose levels. Lately, apart from the common adverse reactions of hypoglycemia and urinary tract infections, cases of diabetic ketoacidosis come to light. Food and Drug administration issued a special warning about this adverse reaction, which include not only empagliflozin but also all drugs of this category. Based on the pharmacological characteristics of this type of drugs and the physiology of SGLT2, several possible mechanisms could be suggested for the development of diabetic ketoacidosis. Inhibition of SGLT2 causes a rapid increase in urinary volume excretion, which lasts more than 24 hours [8]. Also, the decrease in plasma glucose levels, that is caused by these drugs [9], lead to a decrease in plasma insulin levels and a significant increase in plasma glucagon concentrations, because of a diminished paracrine inhibition by insulin and a decreased SGLT2-mediated glucose transport into α-cells [10]. Therefore, SGLT2 inhibitors seem to be associated with euglycemic diabetic ketoacidosis, perhaps as a consequence of their non-insulin dependent glucose clearance, hyperglucagonemia and volume depletion [8].

CONCLUSION
Patients who are treated with SGLT2 inhibitors should be closely monitored for this adverse reaction and clinicians should also be aware of it. Further research should be done in order to minimize the risk of ketoacidosis due to SGLT2 inhibitors. *********

AN INTRODUCTION
Edorium Journals: On Web

About Edorium Journals
Edorium Journals is a publisher of high-quality, open access, international scholarly journals covering subjects in basic sciences and clinical specialties and subspecialties.

Edorium Journals: An introduction
Edorium Journals Team

But why should you publish with Edorium Journals?
In less than 10 words -we give you what no one does.

Vision of being the best
We have the vision of making our journals the best and the most authoritative journals in their respective specialties. We are working towards this goal every day of every week of every month of every year.

Exceptional services
We care for you, your work and your time. Our efficient, personalized and courteous services are a testimony to this.

Editorial Review
All manuscripts submitted to Edorium Journals undergo pre-processing review, first editorial review, peer review, second editorial review and finally third editorial review.

Peer Review
All manuscripts submitted to Edorium Journals undergo anonymous, double-blind, external peer review.

Early View version
Early View version of your manuscript will be published in the journal within 72 hours of final acceptance.

Manuscript status
From submission to publication of your article you will get regular updates (minimum six times) about status of your manuscripts directly in your email.

Favored Author program
One email is all it takes to become our favored author. You will not only get fee waivers but also get information and insights about scholarly publishing.

Institutional Membership program
Join our Institutional Memberships program and help scholars from your institute make their research accessible to all and save thousands of dollars in fees make their research accessible to all.

Our presence
We have some of the best designed publication formats. Our websites are very user friendly and enable you to do your work very easily with no hassle. Something more...
We request you to have a look at our website to know more about us and our services.
We welcome you to interact with us, share with us, join us and of course publish with us.

Invitation for article submission
We sincerely invite you to submit your valuable research for publication to Edorium Journals.

Six weeks
You will get first decision on your manuscript within six weeks (42 days) of submission. If we fail to honor this by even one day, we will publish your manuscript free of charge.*

Four weeks
After we receive page proofs, your manuscript will be published in the journal within four weeks (31 days). If we fail to honor this by even one day, we will publish your manuscript free of charge and refund you the full article publication charges you paid for your manuscript.* This page is not a part of the published article. This page is an introduction to Edorium Journals and the publication services. * Terms and condition apply. Please see Edorium Journals website for more information.