What Diseases and Medications Increase Gallstone Risk?

While anyone can develop gallstones, certain underlying medical conditions and specific medications can increase your risk. Having one of these risk factors does not guarantee you will develop gallstones—many people have multiple risk factors or none at all—and finding a stone does not always mean treatment is necessary if you have no symptoms. These factors typically work by changing the chemical makeup of your bile or by preventing your gallbladder from emptying correctly.

Medical Conditions That Increase Risk

• Hemolytic Anemias (Chronic Red Blood Cell Breakdown): Conditions like sickle cell disease, hereditary spherocytosis, or thalassemia cause red blood cells to break down faster than normal ^[1]. This chronic breakdown releases high amounts of a yellow waste pigment called bilirubin. The excess bilirubin can clump together to form dark, hard “pigment stones” in the gallbladder ^[2].
• Crohn’s Disease and Intestinal Surgery: Crohn’s disease, particularly when it affects the lower small intestine (the terminal ileum) or requires bowel resection surgery, can interfere with how your body reabsorbs bile acids (fluids that help digest fat) ^{[3] [4]}. This disruption can promote cholesterol supersaturation, making cholesterol gallstones more likely to form.
• Advanced Liver Disease (Cirrhosis): Advanced liver scarring, known as cirrhosis, disrupts normal liver function and alters bile production. This significantly increases the odds of developing gallstones, particularly in those with severe cirrhosis or cirrhosis related to hepatitis C ^{[5] [6]}.
• Type 2 Diabetes and Insulin Resistance: People with type 2 diabetes have a higher risk of developing gallstones ^[7]. Research suggests that insulin resistance (when your body doesn’t respond well to insulin) may cause the liver to release more cholesterol into the bile and may also make the gallbladder empty more sluggishly, which can promote bile stasis and stone formation ^[8].
• Prolonged Fasting, Rapid Weight Loss, and Intravenous Nutrition: When you dramatically reduce your food intake—whether due to rapid weight loss diets, prolonged fasting, or receiving total parenteral nutrition (TPN, which is intravenous feeding)—your gallbladder is not stimulated to empty regularly ^[9]. This causes the bile to become stagnant and form sludge or stones ^[10].
• Bile Duct Obstructions: Most gallstones form in the gallbladder, but sometimes stones or sludge form directly in the bile ducts. If a bile duct is blocked by a non-stone issue, such as a stricture (a narrowing of the duct) or a tumor, the stagnant bile can become infected or lead to primary duct stone formation ^[11].

Medications That Can Affect Gallstone Risk

Certain drugs can alter bile composition or affect how well your gallbladder functions. However, you should never stop taking a prescribed medication without first discussing it with your doctor, as the medical benefits of these treatments are important and medication changes must be individualized.

• Ceftriaxone: This specific intravenous antibiotic can bind with calcium in the bile to form a temporary “sludge” or pseudolithiasis (false stones), especially in children, with higher doses, or during prolonged treatment ^{[12] [13]}. While this usually resolves on its own once the medication is finished, it can occasionally cause biliary pain or obstruction.
• Fibrates: These medications are used to lower triglyceride (fat) levels in the blood. They can sometimes increase the amount of cholesterol secreted into your bile, which may raise the risk of gallstone formation ^{[14] [15]}.
• Octreotide and Lanreotide: These drugs (known as somatostatin analogues) are used to treat rare tumors or a growth disorder called acromegaly. Over long periods of use, they can slow down gallbladder emptying ^[16]. While this can lead to gallstone formation, the risk varies by drug, dose, and duration, and many of the detected stones do not cause symptoms ^[17].
• Estrogen Therapy: Exogenous estrogen (estrogen taken from outside the body), such as oral hormone replacement therapy for menopause, can increase cholesterol levels in the bile, which raises the overall risk of developing cholelithiasis (gallstones) ^[18].

Important Safety Warning: When to Seek Urgent Care

If you have gallstones, it is crucial to know the signs of a blocked or infected bile duct (a condition called cholangitis). Seek emergency medical care immediately if you experience:

• Fever or chills
• Severe or persistent pain in your upper right or middle abdomen
• Jaundice (yellowing of your skin or the whites of your eyes)
• Dark urine or pale stools
• Nausea and vomiting
• Confusion or feeling severely ill

These symptoms can indicate a life-threatening complication that requires urgent assessment, not a routine follow-up appointment ^[19].