Novel and Emerging Therapies
Surgery has been the cornerstone of gallstone treatment for many decades (Fogel 2016), but researchers continue to search for new drugs, and new ways to use existing drugs, to prevent gallstones and their complications.
Advances in Non-Surgical Approaches
Medications that affect cholesterol metabolism are currently under investigation for their potential in preventing and treating gallstone disease:
- Ursodeoxycholic acid. As previously noted, ursodeoxycholic acid (or Ursodiol) is currently used to treat gallstone disease in patients for whom surgery is not an option, but widening its use has been proposed, such as to reduce the risk of gallstone formation during pregnancy or rapid weight loss, after abdominal surgery, and in infants requiring long-term total parenteral nutrition (Portincasa 2012; de Bari, Wang, Liu 2014; Stokes 2014; Simic 2014). In addition, synthetic molecules based on ursodeoxycholic acid but with stronger effects have been developed. It is speculated that such bile acid derivatives, and possibly other drugs targeting bile acid activity, may help to better fight gallstone disease (Yu 2016; Halilbasic 2013; Portincasa 2012).
- Metformin. In a study published in 2017, the long-term use of metformin (Glucophage), an anti-diabetic medication, was correlated with a lower risk of gallstones in diabetic subjects (Liao 2017). Metformin's possible gallstone-preventing effects could be related to its ability to improve metabolism. There is also evidence that metformin improves gallbladder motility (Rohde 2016; Isik 2012).
- Statins. Statins are a family of medications used to reduce elevated cholesterol levels. Examples include atorvastatin (Lipitor), simvastatin (Zocor), and rosuvastatin (Crestor). Statins work in part by interfering with the synthesis of cholesterol in the liver, and they also reduce the cholesterol saturation of bile (Cariati 2012; Lioudaki 2011). Findings from animal studies suggest statins may be effective for reducing cholesterol gallstone formation. In humans, statin use has been correlated with a lower risk of gallstone disease and cholecystectomy, but results from randomized clinical trials so far have been mixed (Portincasa 2012; Kan 2014).
- Ezetimibe. Ezetimibe (Zetia) is a cholesterol-lowering drug that inhibits cholesterol absorption across the intestinal wall. This leads to reduced cholesterol secretion by the liver, decreased cholesterol saturation in bile, and prevention of crystallization in the gallbladder (de Bari 2012; Portincasa 2017). Ezetimibe has been found to prevent gallstone formation in animal research, including in mice exposed to high estrogen levels, and is therefore under consideration as an option for preventing and treating gallstones in humans (de Bari, Wang, Portincasa 2014; Portincasa 2017).
Because of their complementary actions, a combination drug (Liptruzet) that contains atorvastatin and ezetimibe has also been suggested as a possible treatment for cholesterol gallstones (Husain 2015).
Surgical approaches are constantly being refined to reduce invasiveness, improve cosmetic outcomes, reduce post-operative pain and recovery time, and maximize effectiveness. One technique that is gaining acceptance is natural orifice transluminal endoscopic surgery (NOTES) cholecystectomy (Abraham 2014; Nemani 2014). This procedure involves the use of a flexible endoscope which is passed through a natural opening in the body, such as the mouth, anus, or vagina, before crossing into the abdominal cavity (Peng 2016). Most NOTES cholecystectomies are done through the vagina (Abraham 2014). A recent advance in NOTES is the addition of laparoscopic assistance, a so-called hybrid NOTES approach (Bernhardt 2017; Mintz 2007).
NOTES cholecystectomies have demonstrated a high degree of safety and a similar complication rate to standard laparoscopic cholecystectomy. In addition, they may be associated with less post-operative pain and may result in less analgesic use and better cosmetic appearance than other types of cholecystectomy (Borchert 2017; Schwaitzberg 2017; Dhillon 2017; Pohlen 2017).