Liraglutide Overdose-Induced Acute Pancreatitis

Liraglutide, a long-acting cardioprotective glucagon-like peptide (GLP)-1 analog, is effective for medical weight loss and glycemic control in type 2 diabetes. It is generally well tolerated with mild side effects. There are few reports on complications from Liraglutide overdose. The aim of this paper is to report the case of a 25-year-old healthy female who presented with acute pancreatitis secondary to Liraglutide overdose and to review the current literature on Liraglutide used for obesity management. The current literature examining the association between acute pancreatitis and Liraglutide use, and Liraglutide overdose are inconclusive. Further research is recommended.


Introduction
Long-acting glucagon-like peptide (GLP-1) analogs, such as Liraglutide, are effective for obesity management and glycemic control. GLP-1 analogs enhance pancreatic beta-cell insulin secretion, delay gastric emptying, and enhance satiety. An overdose of such medication may result in generalized gastrointestinal symptoms like nausea, vomiting, hypoglycemia, and pancreatitis. However, Liraglutide overdose and its association with hypoglycemia and pancreatitis need further elucidation. This paper reports a case of Liraglutide overdose-induced acute pancreatitis.

Case Presentation
A 25-year-old single female with no medical or surgical history presented to the emergency room with a one-day history of progressively worsening sharp epigastric abdominal pain with radiation to the back associated with nausea and non-bloody, nonbilious emesis. The pain was exacerbated with lying supine, but worsened with positional changes, and was unrelieved by paracetamol. The review of systems was negative for fevers, jaundice, pruritis, diarrhea, anorexia, insomnia, mood changes, exposure to sick contacts, trauma, or recent travel. She reported regular menses. The family history was notable for gallstones, but negative for diabetes, hypertension, cancer, and cardiac diseases or autoimmune diseases. She denied any allergies to medications, tobacco use, heavy alcohol use, illicit drug use, or sexual activity.
The patient reported a two-month history of unsupervised Liraglutide use for medical weight loss. She had obtained the medication without a prescription and had progressively increased the dose until she reached 3 mg, at which point she could not tolerate it due to nausea and vomiting. The medication was discontinued for a month. She resumed the medication at 2.4 mg on the day of presentation to the emergency room, with the onset of symptoms soon thereafter.
On initial examination, the patient was conscious, alert, and oriented to time, place, and person. She was lying in bed in severe pain. The cardiopulmonary exam was unremarkable. Abdominal examination demonstrated diffuse tenderness with focal intensification in the epigastrium with negative Murphy's sign. The extremity exam was negative for clubbing, cyanosis, or edema.
As per the patient, she went to a different facility before presenting to our hospital and lipase was more than 900 and amylase was more than 200. However, the patient's vital signs and laboratory parameters are summarized in Table 1.  Imaging was performed as well. Abdominal and chest radiographs were unremarkable. Abdominal ultrasound was negative for cholelithiasis, cholecystitis, or biliary ductal dilatation (Figures 1, 2). Further, no computed tomography was ordered for the patient.

CBD: Common Bile Duct
The patient was admitted to the general surgery services as a case of acute pancreatitis for symptomatic management. She was managed by bowel rest, analgesia, intravenous fluids, antibiotics, and Clexane. The patient showed improvement within 48 hours and was safely discharged with educational materials and follow-up.
The class of medications is generally well-tolerated, and the side-effect profile is mostly gastrointestinal in nature (i.e., nausea, vomiting, and diarrhea). Injection site reactions have been reported, and they are more common with Exenatide formulations and Albiglutides. Reports of hypoglycemic episodes are rare [3]. Pancreatitis is a suspected side-effect of GLP-1 RAs; however, few studies and case reports of GLP-1 RA overdose and its association with acute pancreatitis have been described [4]. A recent case report of autopsy demonstrated pathologic pancreatic changes in patients with diabetes who were treated with incretin-based drugs such as Liraglutide [5]. Furthermore, a recent meta-analysis had near-unanimous reporting of adverse gastrointestinal symptoms suggestive of pancreatitis, but there was no formal diagnosis of acute pancreatitis in the acute phase of illness or in the follow-up period [4][5][6][7][8][9][10][11][12][13][14][15][16]. Given these considerations, future research, and evaluation of the short-and long-term consequences of GLP-1RA use and overdose are highly recommended [17].

Conclusions
GLP-1 RA, Liraglutide. is a widely used medication for the treatment of type 2 diabetes mellitus. Also, Liraglutide is effective for weight reduction, glycaemic control, and prevention of adverse cardiac events. Common side effects of Liraglutide are nausea, vomiting, and gastrointestinal discomfort. However, hypoglycemia and pancreatitis are reported but not proven to be associated with Liraglutide overdose. Therefore, further investigation is necessary to determine an association between Liraglutide, Liraglutide overdose, and acute pancreatitis.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.