Endocrine Abstracts

Introduction

Glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the two novel classes of anti-diabetic agents with compelling efficacy, in terms of glucose-lowering and cardio-renal protection. Euglycemic diabetic ketoacidosis (EDKA) is a serious rare adverse effect of SLT2i while the use of GLP-1RA has been scarcely linked with acute pancreatitis in humans.

Case presentation

We present the case of a 50-year old, overweight man who was admitted to the Emergency Department due to diffuse abdominal pain radiating to the back, nausea, appetite loss and bile vomiting. He had a 20-year history of Type 2 Diabetes (T2D) and was on triple anti-diabetic regimen with dulaglutide, empagliflozin and metformin which he continued to take, despite a marked decrease in food intake over the last 5 days. Clinical examination was remarkable for rapid heart rate, Kussmaul breathing, signs of extracellular volume depletion (dry skin and mucosa) and breath smell of acetone. Initial laboratory work-up revealed metabolic acidosis (pH 7.053) with increased anion gap (22.3 mmol/l), ketonaemia (4.9 mmol/l) and ketonuria (4+ in urine dipstick), in the setting of mild hyperglycaemia (glucose 204 mmol/l) and normal renal function (eGFR 126 ml/min/1.73 m²). Meanwhile, computed tomography of the abdomen revealed misty mesentery and significant stomach dilation; therefore, a nasogastric tube for drainage was placed. EDKA was managed with intravenous administration of 5% dextrose solution, fixed-rate insulin infusion, 0.9% normal saline and potassium. Following the above protocol, b-hydroxybutyric acid gradually decreased, blood glucose level was maintained stable (130–180 mg/dl), and acidosis was reversed within 12 hours (pH 7.330). However, serum and urine amylase demonstrated a gradual increase during the first 24 hours (peak levels of 654 U/l and 1423 U/l respectively). Gastroenterology review established the diagnosis of acute pancreatitis, thus intravenous esomeprazole and metoclopramide were initiated. The patient demonstrated rapid clinical improvement and feeding restarted after 48 hours. As for the cause of acute pancreatitis, all other etiologies (lithiasis, alcohol, autoimmune, trauma) were excluded and it was attributed to GLP-1RA use.

Conclusions

The possibility of EDKA due to SGLT2i must be kept in mind when evaluating a patient with long standing T2D and unexplained metabolic acidosis. Acute pancreatitis due to GLP-1RA exists in humans, although several studies did not verify an increased risk. This case highlights that all anti-diabetic agents must be applied in a patient-tailored way, accompanied by appropriate sick day rules.