Euglycemia despite a sodium glucose co-transporter 2 inhibitor overdose

Muhammad Akbar Baig, Joshua Nogar

NorthShore University Health System, Manhasset, NY 11030, USA

Dear editor,

Sodium glucose co-transporter 2 inhibitors (SGLT2I)reduce the majority of reabsorption of glucose in the proximal tubules, which reduces blood glucose levels by allowing excretion of excess glucose in the urine.By inhibiting glucose reabsorption, they increase the osmotic pressure of urine resulting in diuresis which can cause a reduction of blood pressure.Fortunately, as these drugs are not directly implicated in altering glucose metabolism or causing insulin secretion, SGLT2I monotherapy does not result in severe hypoglycemia.

Physicians are now prescribing SGLT2Is for the treatment of diabetes as they reduce the incidence of diabetic complications, including all-cause mortality.However, there is less experience regarding the clinical course in the event of an SGLT2I overdose. Here we report our experience with an elderly woman who presented after an overdose of an ertugliflozin, an SGLT2I.

CASE

A 60-year-old female with a past medical history of diabetes, hypertension and hypothyroidism presented to the emergency department with complaints of dizziness.Five hours before presentation, she accidentally ingested a total of 150 mg of her recently expired ertugliflozin which she had dissolved in a cup of water with the intent of pouring down the kitchen sink.

On admission her vital signs were: heart rate 93 beats/min; blood pressure 159/74 mmHg (1 mmHg=0.133 kPa); respiratory rate 18 breaths/min; saturation of peripheral oxygen (SpO) 99% on room air and body temperature 37 ℃. Her physical examination was unremarkable. Laboratory evaluation showed: glucose 126 mg/dL, urea nitrogen 13 mg/dL,and creatinine 0.6 mg/dL. The serum electrolytes, liver function test and blood gas were within normal range.

The patient was also taking metformin, dulaglutide and glimepiride for her diabetes control and had taken her routine doses prior to the overdose. Due to the combination of various oral hypoglycemic agents, we chose to admit the patient for observation and regular blood glucose monitoring every four hours for a total duration of twelve hours during the course of which her blood glucose levels remained between 115 and 196 mg/dL (Figure 1).

The patient’s symptoms improved during her hospital stay and she remained hemodynamically stable with systolic blood pressure readings between 125 and 159 mmHg and diastolic blood pressure readings between 65 and 83 mmHg. Endocrinology consultation was also sought and the patient’s oral hypoglycemic medications were modified prior to discharge. Her routine dose of ertugliflozin was reduced and she was educated regarding the appropriate timings and doses of her medications.

DISCUSSION

A retrospective review of SGLT2I overdoses reported to 13 poison centers showed that majority of the cases did not develop any symptoms and none reported hypoglycemia.Based on the small number of SGLT2I overdoses reported so far, individuals who unintentionally ingest a double dose will either remain asymptomatic or may have mild adverse effects such as nausea, vomiting, or dizziness.Based on Poison Control Center data, a small number of pediatric exploratory ingestions have resulted in no more than minor effects with mild hypoglycemia.On the other hand, intentional ingestion of a large dose of these medications can cause one to develop symptoms such as confusion, nausea,vomiting, tachycardia, hypertension and incontinence.

Figure 1. The patient’s serial serum glucose measurements at four different time points.

Our case presented after an overdose of ertugliflozin with other glucose-lowering agents that were concomitantly present at baseline, including a sulfonylurea, which placed her at a much higher risk for significant hypoglycemic events. She was five hours from her time of ingestion and was hospitalized for twelve hours due to the prolonged half-life of ertugliflozin.

Per standard guidelines, upon the identification of hypoglycemia, treatment would have required immediate reversal of low glucose levels by providing complex carbohydrates in a meal if the patient would be able to eat or intravenously if there is depressed consciousness.For refractory hypoglycemia, subcutaneous/intravenous octreotide is used, and the patient is monitored more frequently for hypoglycemia.Fortunately, our patient did not experience hypoglycemia during her period of observation. Although the incidence of hypoglycemia with SGLT2Is is low, we speculate another potential mechanism that can be explained as a result of the reduced glomerular filtration rate secondary to her routine antihypertensive agent which was an angiotensin converting enzyme inhibitor (ACEI), enalapril. ACEI causes renal efferent arteriolar vasoconstriction which increases filtration fraction allowing greater solute reabsorption in the proximal tubules.This protective effect is in addition to the already established advantages of prescribing a combination therapy of SGLT2 drugs with ACEI in diabetic patients for preventing cardiorenal events.

CONCLUSIONS

SGLT2Is are prescribed either as mono or combination drug therapy, thus raising concerns regarding intoxication. Additional cases detailing SGLT2I overdoses would help clarify the mechanisms underlying intoxication and approach to their management.

None.

This study was approved by the Ethics Committee of the hospital.

Conflicts of interest: The authors have no financial or other conflicts of interest related to the submitted article.

MAB is responsible for concept, drafting, proof reading and finalizing the manuscript. JN is responsible for proof reading and finalizing the manuscript. Both authors participated in the care of the patient.