Can Ozempic Cause Appendicitis?
Based on current evidence, there is no established causal relationship between Ozempic (semaglutide) and appendicitis, though isolated case reports exist. The major gastrointestinal safety concerns with semaglutide that are well-documented include pancreatitis, biliary disease (cholelithiasis and cholecystitis), and delayed gastric emptying—not appendicitis 1.
Established Gastrointestinal Safety Profile
The recognized gastrointestinal adverse effects of semaglutide include:
Biliary disease: GLP-1 receptor agonists are associated with increased risk of gallbladder disease, including cholelithiasis and cholecystitis 1. The 2022 AGA guidelines specifically note that clinicians should evaluate for gallbladder disease if these conditions are suspected and avoid use in at-risk individuals 1.
Pancreatitis: Acute pancreatitis has been reported in clinical trials, though causality has not been definitively established 1, 2. Guidelines recommend not initiating semaglutide in patients at high risk for pancreatitis and discontinuing if pancreatitis is suspected 1.
Delayed gastric emptying: Semaglutide significantly delays gastric emptying, which can lead to nausea, vomiting, and retained gastric contents 1, 3. This effect is most pronounced during initial treatment and may develop tachyphylaxis with continued use 4.
Evidence Regarding Appendicitis
The available evidence on appendicitis is extremely limited:
One case report describes a 48-year-old woman who developed appendicitis several months after starting Ozempic, requiring appendectomy 5. The authors hypothesized that GLP-1 receptor agonists' gastrointestinal effects might theoretically increase risk of appendicitis through mechanisms involving obstruction or altered motility 5.
However, this represents a single case report with no controlled data, and the authors themselves acknowledge that "minimal data are available to suggest significant causation" 5.
Critically, appendicitis is not mentioned in major clinical guidelines from the American Diabetes Association, American Gastroenterological Association, or European Society of Cardiology as a recognized adverse effect of semaglutide 1.
The comprehensive safety review of semaglutide published in 2021 does not list appendicitis among adverse events, despite discussing gastrointestinal, pancreatic, and biliary complications in detail 2.
Clinical Implications
When evaluating abdominal pain in patients on semaglutide, prioritize the following differential diagnoses:
- Biliary disease (cholelithiasis/cholecystitis) - well-established association requiring evaluation if suspected 1
- Pancreatitis - reported but causality unestablished; discontinue if suspected 1
- Gastroparesis/delayed gastric emptying - common, particularly during dose titration 1, 3
- Common gastrointestinal side effects - nausea, vomiting, diarrhea, constipation, abdominal pain 1
If appendicitis is clinically suspected based on examination findings (focal right lower quadrant tenderness, rebound, guarding) and imaging, manage according to standard surgical protocols. The presence of semaglutide therapy should not alter your clinical suspicion or management of appendicitis, as there is insufficient evidence to suggest a causal relationship 5.
Important Caveats
The serious adverse events reported in semaglutide trials included abdominal pain, but appendicitis was not specifically highlighted as a pattern 1.
Post-marketing surveillance and adverse event reporting systems have not identified appendicitis as a signal requiring regulatory action or label changes 5.
Do not withhold appropriate evaluation for appendicitis in patients on semaglutide, but recognize this is likely coincidental rather than drug-related based on current evidence 5, 2.