SAT-612 - Lipase Elevation with Glucagon-Like Peptide-1 Receptor Agonist - to Treat or Not to Treat?

Introduction
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained significant
popularity in the United States owing to their efficacy in the treatment of Type 2
Diabetes Mellitus, obesity and reducing major adverse cardiovascular events in adults
with type 2 diabetes and established cardiovascular disease. They are also being used
in the management of chronic kidney disease and obstructive sleep apnea. Studies
demonstrate that GLP-1 RAs may increase lipase levels in the absence of pancreatitis.
It is thought to be due to adaptive pancreatic growth rather than inflammation. Lipase
levels typically rise modestly (18%-31% above baseline), with most elevations below 3x
upper limit of normal (ULN). In the SCALE trials, only 2.9% of patients on liraglutide
3.0mg had lipase elevations of ≥3x ULN compared to 1.5% on placebo.
Case
We present the case of a 58-yr old male with a history of type 2 diabetes mellitus
complicated by obesity and microalbuminuria, hypertriglyceridemia, Metabolic
dysfunction- associated steatotic liver disease, Hashimoto’s thyroiditis and nontoxic
multinodular goiter who was started on semaglutide. The dose was gradually increased
from 0.5 mg to 2.0 mg with good clinical response and without adverse effects. Lipase
was checked with routine labs and was high at 372U/L (normal 12-53). Triglycerides
were 290 mg/dl (normal 15-150). However, the patient denied symptoms of abdominal
pain, nausea or vomiting, and history of alcohol use. Semaglutide was held for two
weeks and lipase levels decreased to 90 U/L. MRI of pancreas was done and was
normal. The patient was evaluated by Gastroenterology and restarted on semaglutide
with instructions to follow up if he experienced gastrointestinal side effects. Lipase
levels were repeated two months later and came back high at 653 U/L (≥ 8x ULN) with
patient continuing to be asymptomatic. Semaglutide was held again with follow up
lipase showing improvement to 62 U/L. Since the patient was asymptomatic,
Gastroenterology advised the patient to continue semaglutide with close clinical
monitoring.

Discussion
This case highlights the clinical dilemma of marked lipase elevation in an asymptomatic
patient receiving a GLP-1 RA. It also underscores an important practical point: routine
lipase monitoring in asymptomatic patients on GLP-1 RAs can lead to unnecessary
treatment interruptions, testing, and patient anxiety. In conclusion, this case reinforces
that isolated, even marked, lipase elevation during GLP-1 RA therapy may not mandate
drug discontinuation in the absence of symptoms or imaging evidence of pancreatitis.
Clinicians should avoid routine pancreatic enzyme testing in asymptomatic patients and
focus on symptom-based evaluation.

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