Cholecystokinin
The gut hormone that empties the gallbladder after a meal, given as sincalide to make that happen on a scan
Cholecystokinin is a family of gut and brain peptides released after eating that contracts the gallbladder, drives pancreatic enzyme secretion and signals fullness. Its C-terminal octapeptide, CCK-8, is FDA-approved as Kinevac (sincalide), used diagnostically to empty the gallbladder or stimulate the pancreas. It is not approved as a treatment.
What is it?
Cholecystokinin was discovered in 1928 in intestinal extracts as the factor that contracts the gallbladder. It is a family of peptides, CCK-58 down to CCK-8, made by endocrine I-cells of the small intestine and by neurons in the brain, all acting on CCK1 and CCK2 receptors. It stimulates pancreatic enzymes and gut motility, signals satiety, inhibits stomach acid, and in the brain is a major neurotransmitter.
Its gallbladder action is precise. Infused into five healthy people at a rate that matched normal after-meal blood levels, CCK-8 shrank the gallbladder by 76%; higher rates reached 87 to 88%. That makes it a natural diagnostic tool: Kinevac, synthetic CCK-8 known as sincalide, is approved to contract the gallbladder for imaging or bile sampling, to stimulate pancreatic secretion alongside secretin, and to speed a barium meal.
Its main use is the gallbladder scan. During cholescintigraphy, sincalide is infused and the fraction of tracer the gallbladder ejects is measured. How it is infused matters: a multicentre study in 60 healthy volunteers found a 60-minute infusion of 0.02 µg/kg gave the most reproducible result, with 38% as the lower limit of normal, and that became the consensus standard. Whether a low result predicts who will feel better after gallbladder removal is still argued; some studies found it did not.
Supply has been fragile. When the branded product was unavailable, compounded versions filled the gap, and two patients scanned with each gave very different ejection fractions. It has also been tried in ERCP, to help find the bile duct opening, and in patients on parenteral nutrition to keep bile moving, without enough evidence for routine use.
Recent experiments use it as a probe. In ten healthy men, CCK-induced gallbladder emptying raised GLP-1, an effect metformin added to. In 15 men, GLP-2 completely blocked the contraction CCK caused, and GLP-1 drugs such as exenatide and albiglutide blunted it. It signals satiety after meals, but it is not approved as a treatment for anything.
Mechanism of Action
Sincalide is CCK-8, the C-terminal octapeptide of cholecystokinin; given intravenously it contracts the gallbladder much as a meal does (label).
Gallbladder contraction
Stimulates the gallbladder to contract and shrink, emptying bile as endogenous CCK does after food (label).
Pancreatic secretion
Stimulates pancreatic enzyme secretion; with secretin it raises secretion volume, bicarbonate and enzymes, so a duodenal sample reflects pancreatic function (label).
Gut motility
Increases intestinal motility and causes pyloric contraction, slowing gastric emptying; this is used to speed a barium meal (label).
Published Research
These are the studies that describe cholecystokinin in people, read from their PubMed abstracts: three infusion studies and a review.
It empties the gallbladder
CCK-8 was infused into five healthy people. At a rate giving normal after-meal blood levels the gallbladder shrank 76%; higher rates reached 87 to 88%, and volume recovered within 30 minutes.
Gallbladder emptying releases GLP-1
In ten healthy men, CCK-induced gallbladder emptying and metformin each raised GLP-1, and together their effects added up; glucose and insulin did not change.
GLP-2 blocks it
In a crossover study in 15 healthy men, GLP-2 alone did not change gallbladder volume but completely abolished the strong contraction caused by a CCK infusion.
Exenatide blunts its gallbladder effect
In healthy volunteers given a cholecystokinin infusion, one 10 µg dose of exenatide lowered the maximum gallbladder ejection fraction to 28.8% against 46.1% on placebo.
Albiglutide does the same
In 17 healthy volunteers, albiglutide 50 mg kept the gallbladder larger and lowered its ejection fraction during a cholecystokinin infusion against placebo.
Setting the standard infusion
In 60 healthy volunteers at four centres, a 60-minute infusion of 0.02 µg/kg gave the least variable gallbladder ejection fraction (coefficient of variation 19% against 35% and 52% for 30- and 15-minute infusions), with a lower limit of normal of 38%.
Not a gallbladder stress test
In patients with gallstones and controls, ejection fraction and emptying rates did not separate those who benefited from cholecystectomy from those who did not; the authors concluded an experienced surgeon's judgement remained the better guide.
An aid during ERCP
In a prospective, non-randomised series, sincalide was used in 32 of 136 ERCPs and helped obtain a cholangiogram after initial failure in 12 of 19 patients; the author noted perseverance alone may explain some of the success.
Compounded against branded sincalide
Two patients had ejection fractions of 11% and 24% with compounded sincalide during a shortage, and 32% and 72% when repeated three days later with the branded product.
From gut hormone to messenger
CCK was found in 1928 as a gallbladder factor; its peptides act on CCK1 and CCK2 receptors in the gut, pancreas, brain and other tissues, stimulating enzymes, motility and satiety and inhibiting stomach acid.
Parenteral nutrition gallbladder disease
Across five human studies, 0.04 µg/kg three times daily increased bile flow and lowered bilirubin in parenteral nutrition-associated cholestasis, but not in advanced liver disease; routine use could not be recommended.
Thirty-two years of the test
A review of sincalide cholescintigraphy found studies divided on whether a low ejection fraction predicts relief from gallbladder removal, and noted the consensus standard: 0.02 µg/kg over 60 minutes, with under 38% abnormal.
Dosing Data
Kinevac is a diagnostic injection: 0.02 µg/kg intravenously over 30 to 60 seconds to contract the gallbladder, or an infusion over 50 minutes to reduce stomach upset.
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Side Effects & Contraindications
Reported Side Effects
From the Kinevac label.
Contraindications & Cautions
Set by the Kinevac label.
Legal Status
CCK-8 is FDA-approved as a diagnostic agent.
Frequently Asked Questions
?What is cholecystokinin?
A gut and brain peptide family released after meals that contracts the gallbladder, stimulates the pancreas and signals fullness.
?Is it a drug?
Its octapeptide, CCK-8, is approved as Kinevac (sincalide) for diagnostic tests of the gallbladder and pancreas.
?Does it cause weight loss?
It signals satiety, but it is not approved as a weight-loss treatment.
?How strongly does it act?
At normal after-meal levels, infused CCK-8 shrank the gallbladder by 76% in healthy people.
?What is a sincalide gallbladder scan?
A nuclear medicine test: a tracer collects in the gallbladder, sincalide is infused, and the share of tracer it ejects is measured. With the standard 60-minute infusion of 0.02 µg/kg, under 38% is abnormal.
References
- [fda-pi] KINEVAC (sincalide) for injection Prescribing Information, sections 1, 4, 6 and 11 (DailyMed version 13, effective October 18, 2023; read September 30, 2026).
- [pubmed] Byrnes DJ, et al. "Cholecystokinin and gallbladder contraction: effect of CCK infusion." Peptides, 1981;2 Suppl 2:259-62. PMID: 6283495.
- [pubmed] Rohde U, et al. "Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses." J Clin Endocrinol Metab, 2016;101(5):2076-83. PMID: 27003305.
- [pubmed] Lange AH, et al. "Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men." J Clin Endocrinol Metab, 2024;110(1):123-129. PMID: 38888179.
- [pubmed] Rehfeld JF. "Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger." Front Endocrinol (Lausanne), 2017;8:47. PMID: 28450850.
- [pubmed] Gibbs J, et al. "Cholecystokinin decreases food intake in rats." J Comp Physiol Psychol, 1973;84(3):488-95. PMID: 4745816.
- [other] US FDA, Drugs@FDA (openFDA): KINEVAC (sincalide), NDA 017697, Bracco, prescription. Read September 30, 2026.
- [clinical-trial] Keller J, et al. "Effect of exenatide on cholecystokinin-induced gallbladder emptying in fasting healthy subjects." Regul Pept, 2012;179(1-3):77-83. PMID: 22960288.
- [clinical-trial] Shaddinger BC, et al. "Effect of Albiglutide on Cholecystokinin-Induced Gallbladder Emptying in Healthy Individuals: A Randomized Crossover Study." J Clin Pharmacol, 2017;57(10):1322-1329. PMID: 28543352.
- [pubmed] Ziessman HA, et al. "Sincalide-stimulated cholescintigraphy: a multicenter investigation to determine optimal infusion methodology and gallbladder ejection fraction normal values." J Nucl Med, 2010;51(2):277-81. PMID: 20080900.
- [pubmed] Gani JS. "Can sincalide cholescintigraphy fulfil the role of a gall-bladder stress test for patients with gall-bladder stones?." Aust N Z J Surg, 1998;68(7):514-9. PMID: 9669367.
- [pubmed] Weston AP. "Sincalide: a cholecystokinin agonist as an aid in endoscopic retrograde cholangiopancreatography--a prospective assessment." J Clin Gastroenterol, 1997;24(4):227-30. PMID: 9252846.
- [pubmed] Guarasci DT, et al. "Compounded versus proprietary sincalide for evaluation of gallbladder ejection fraction." Ann Pharmacother, 2004;38(3):428-32. PMID: 14755063.
- [pubmed] Prescott WA Jr, et al. "Sincalide in patients with parenteral nutrition-associated gallbladder disease." Ann Pharmacother, 2004;38(11):1942-5. PMID: 15316105.
- [pubmed] Ziessman HA. "Sincalide cholescintigraphy--32 years later: evidence-based data on its clinical utility and infusion methodology." Semin Nucl Med, 2012;42(2):79-83. PMID: 22293163.
Sources & Citations
Studies were read from their PubMed abstracts; the Kinevac label (DailyMed version 13, effective October 18, 2023) was read October 6, 2026.
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