From the Guidelines
Metformin-induced abdominal pain typically presents as discomfort in the upper middle or lower abdomen, often described as cramping, bloating, or a general sense of gastrointestinal distress, and is a common side effect that occurs in approximately 25% of patients taking metformin, particularly when first starting the medication or after dose increases, as reported in the most recent study 1. This side effect is frequently accompanied by other gastrointestinal symptoms including diarrhea, nausea, vomiting, and excessive gas.
- The symptoms result from metformin's action in the intestines, where it alters bile acid metabolism, changes gut microbiota composition, and increases intestinal serotonin secretion, all of which affect gut motility and secretion.
- Taking metformin with meals can help reduce these symptoms, as can starting with a low dose (such as 500mg once daily) and gradually increasing to the target dose (typically 1000-2000mg daily divided into two doses).
- Extended-release formulations of metformin often cause less gastrointestinal distress than immediate-release versions. Most patients experience improvement in these symptoms within 2-3 weeks as their bodies adjust to the medication, but persistent severe abdominal pain, especially if accompanied by severe vomiting or signs of dehydration, warrants medical attention to rule out lactic acidosis, a rare but serious complication, as noted in 1. The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extended-release formulation, as stated in 1. It is essential to consider the patient's individual factors, such as efficacy, hypoglycemia risk, effect on weight, side effects, cost, and patient preferences, when choosing pharmacologic agents, as recommended in 1. Overall, metformin is a commonly used and effective medication for the treatment of type 2 diabetes, and its benefits, including reducing the risk of microvascular complications, cardiovascular events, and death, outweigh the risks of gastrointestinal side effects, as reported in 1.
From the FDA Drug Label
These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence;
- Abdominal pain is a symptom of metformin-associated lactic acidosis.
- The location of the abdominal pain is not specified in the drug label.
- Symptoms that may accompany abdominal pain include:
- Malaise
- Myalgias
- Respiratory distress
- Increased somnolence 2
From the Research
Metformin Induced Abdominal Pain
- Metformin is associated with a higher risk of abdominal pain, diarrhea, and nausea compared to control 3
- The risk of abdominal pain is highest when metformin is compared to placebo 3
- Abdominal pain is a common gastrointestinal symptom reported by patients taking metformin, with 30% of patients describing GI symptoms, most commonly abdominal pain and diarrhea 4
- Bloating, nausea, and abdominal pain are significantly associated with medication nonadherence, as measured by the medication possession ratio (MPR) [<80%] 5
Location and Symptoms of Abdominal Pain
- The location of metformin-induced abdominal pain is not specifically stated in the studies, but it is described as part of the gastrointestinal adverse events associated with metformin therapy 6, 3, 7, 5, 4
- Symptoms associated with metformin-induced abdominal pain include diarrhea, nausea, flatulence, indigestion, vomiting, and bloating 6, 3, 7, 5, 4
- The severity of abdominal pain and other GI symptoms can impact health-related quality of life (HRQoL) and medication adherence in patients with type 2 diabetes 5