From the Guidelines
Metformin can lower blood glucose levels independently, with a reduction in HbA1c levels by 1.0% to 1.5% versus placebo, as shown in the most recent study from 2019 1. The mechanism of action of metformin involves reducing glucose production in the liver, improving insulin sensitivity in muscles, and decreasing intestinal absorption of glucose.
- The standard starting dose is 500 mg once or twice daily, which can be gradually increased to a maximum of 2000-2550 mg daily, divided into two or three doses.
- Metformin is most effective when taken with meals to minimize gastrointestinal side effects like nausea and diarrhea.
- Unlike insulin or sulfonylureas, metformin doesn't stimulate insulin release, which is why it rarely causes hypoglycemia on its own, as supported by the 2018 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 1. However, when combined with other diabetes medications, exercise, or insufficient food intake, the risk of low blood sugar increases.
- Patients should monitor their blood glucose levels regularly, especially when starting metformin or adjusting the dose, and should be aware of hypoglycemia symptoms such as shakiness, sweating, confusion, and dizziness. It is also important to note that metformin has a good safety profile, with rare cases of lactic acidosis reported, usually in the setting of severe illness or acute kidney injury, and may result in lower serum vitamin B12 concentration, requiring periodic monitoring and supplementation if levels are deficient 1.
From the Research
Mechanism of Action
- Metformin lowers blood glucose levels by reducing glucose production in the liver, decreasing insulin resistance, and increasing insulin sensitivity 2, 3, 4.
- It acts by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output 3.
- Metformin does not cause hypoglycemia like sulfonylureas and is safe when cautions and contraindications are followed 5, 6.
Efficacy
- Metformin is an effective agent in the oral treatment of non-insulin-dependent diabetes mellitus and can lower HbA1c by around 1.5% when used as monotherapy 3.
- It has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 2, 5, 6.
- Metformin can reduce microvascular complication risk and its use is associated with a lower cardiovascular mortality compared with sulfonylurea therapy 4.
Safety and Tolerability
- Metformin is usually well tolerated, with the most common side effects being gastrointestinal 3.
- Concerns that it may increase the risk of lactic acidosis have largely been allayed, with recent studies suggesting less than one case per 100,000 treated patients 3, 6.
- Metformin can be safely used in the elderly, provided prescribing precautions are followed, and dosing is conservative 6.