What is the relationship between Metformin (Biguanide) and pancreatitis?

From the Guidelines

Metformin is not associated with an increased risk of pancreatitis and can be safely used in patients with a history of pancreatitis, as evidenced by the most recent and highest quality study 1.

Key Points

• Metformin is considered a first-line treatment for type 2 diabetes due to its efficacy, safety, and low cost 1.
• The medication works by decreasing hepatic glucose production and improving insulin sensitivity in peripheral tissues, which does not directly impact pancreatic inflammation pathways.
• Unlike some other diabetes medications, such as GLP-1 receptor agonists or DPP-4 inhibitors, metformin has not shown a significant risk for triggering pancreatic inflammation 1.
• The standard dosing of metformin ranges from 500-2000 mg daily, usually divided into two doses with meals to minimize gastrointestinal side effects.
• If a patient develops acute pancreatitis, it may be prudent to temporarily hold metformin during the acute phase, particularly if there is significant nausea, vomiting, or risk of dehydration, but this is due to general illness concerns rather than metformin specifically worsening pancreatitis.

Considerations

• Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily 1.
• The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea, which can be mitigated by gradual dose titration and/or using extended-release formulation 1.
• Metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m², but very high circulating levels have been associated with lactic acidosis, particularly when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² 1.

Recommendations

• Metformin can typically be continued in patients with a history of pancreatitis and may even be preferred as a first-line agent for diabetes management in these patients.
• For patients with both diabetes and pancreatitis, maintaining good glycemic control is important, and metformin can help achieve this without adding pancreatic risk.
• It is essential to monitor patients for potential side effects, such as gastrointestinal intolerance and lactic acidosis, and adjust the treatment plan accordingly.

From the Research

Metformin and Pancreatitis

• Metformin treatment is associated with a lower risk of severe hypoglycaemia, major adverse cardiovascular events, and all-cause mortality in patients with post-pancreatitis diabetes mellitus 2.
• Among biguanides, metformin has been cited in case reports as a potential cause of acute pancreatitis, particularly in patients with renal insufficiency 3.
• A case report has been published where metformin induced acute pancreatitis was precipitated by renal failure, highlighting the importance of monitoring renal function in patients taking metformin 4.
• A nationwide retrospective cohort study from Taiwan found that metformin was associated with a lower risk of acute pancreatitis compared to sulfonylureas, and low-dose metformin was associated with a lower risk of pancreatitis compared to high-dose metformin 5.
• While metformin is not directly linked to an increased risk of pancreatitis, the use of dipeptidyl peptidase-4 inhibitors (DPP-4 inh) in combination with metformin may increase amylase and lipase levels without clinical findings of acute pancreatitis, and should be used with caution in patients at risk for pancreatitis and pancreatic cancer 6.

Key Findings

• Metformin is generally considered safe and effective for the treatment of post-pancreatitis diabetes mellitus 2.
• Patients with renal insufficiency may be at increased risk of acute pancreatitis when taking metformin 3, 4.
• The risk of acute pancreatitis associated with metformin is lower compared to sulfonylureas 5.
• Combination therapy with DPP-4 inh and metformin requires careful monitoring for pancreatitis risk factors 6.