From the Guidelines
Metformin offers numerous clinical benefits beyond its primary role in glycemic control, including reducing risks of microvascular complications, cardiovascular events, and death, as well as having beneficial effects on weight management and potentially reducing the risk of metabolic dysfunction–associated liver disease (MASLD) or metabolic dysfunction–associated steatohepatitis (MASH) 1.
Clinical Benefits of Metformin
The medication is effective and safe, inexpensive, and widely available, making it a commonly used first-line treatment for type 2 diabetes.
- Metformin reduces the risk of microvascular complications, cardiovascular events, and death in patients with type 2 diabetes.
- It has beneficial effects on weight management, typically causing modest weight loss, and does not cause hypoglycemia.
- The medication is also more effective than dipeptidyl peptidase 4 (DPP-4) inhibitors in lowering A1C and weight when used as monotherapy.
Safety and Dosage
The principal side effects of metformin are gastrointestinal intolerance, which can be mitigated by gradual dose titration and/or using extended-release formulation.
- The standard dosing begins at 500 mg once or twice daily with meals, gradually increasing to a maximum of 2000-2550 mg daily as tolerated.
- Metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m², but it is associated with an increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy.
Comparison with Other Medications
Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality 1.
- Metformin is more effective than DPP-4 inhibitors in lowering A1C and weight when used as monotherapy.
- The medication has a better safety profile and lower cost compared to other glucose-lowering agents, making it a valuable first-line therapy for type 2 diabetes.
From the Research
Clinical Benefits of Metformin Beyond Glycemic Control
The clinical benefits of metformin beyond glycemic control include:
- Improvement in serum lipid profiles 2
- Cardiovascular benefits, with a 36% relative risk reduction in all-cause mortality and a 39% relative risk reduction in myocardial infarction 3
- Weight management, as metformin can help stabilize or decrease weight 2, 3
- Potential reduction in the risk of cancer development, inhibition of neurodegenerative disease, and prolongation of lifespan 4
- Cardioprotective and nephroprotective effects 3, 4
Metformin's Mechanism of Action
Metformin's mechanism of action is based on:
- Reducing glucose production in the liver 2, 5
- Decreasing insulin resistance 2, 5
- Increasing insulin sensitivity 2, 5
- Enhancing peripheral uptake of glucose 3
Comparison with Other Antidiabetic Agents
Metformin has been compared to other antidiabetic agents, including:
- Sulfonylureas, which stimulate insulin secretion and can cause hypoglycemia and weight gain 2
- Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which have been shown to have cardioprotective and renoprotective benefits 6
- Insulin, which can be used in combination with metformin to improve glycemic control 2