From the Guidelines
Metformin increases insulin sensitivity by decreasing glucose production in the liver, reducing intestinal glucose absorption, and improving insulin sensitivity in muscle and fat cells, and it is recommended as the first-line treatment for type 2 diabetes, with a typical starting dose of 500 mg once or twice daily with meals, gradually increasing to a target dose of 1000 mg twice daily (maximum 2550 mg daily) to minimize gastrointestinal side effects. The medication works through multiple mechanisms, primarily by activating AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism and improves glucose utilization throughout the body 1. For treating type 2 diabetes, metformin is typically started at a low dose and gradually increased to minimize gastrointestinal side effects, with extended-release formulations available for once-daily dosing 1. Some key points to consider when prescribing metformin include:
- Starting with a low dose and gradually increasing as needed and tolerated
- Monitoring kidney function, as metformin is contraindicated in severe kidney disease (eGFR <30 mL/min)
- Taking metformin with food to reduce stomach upset
- Being aware of potential side effects, such as diarrhea, nausea, and abdominal discomfort, which often improve with time
- Considering periodic measurement of vitamin B12 levels, as long-term use of metformin may be associated with biochemical vitamin B12 deficiency 1. It is essential to individualize treatment and consider patient-specific factors, such as kidney function and potential side effects, when prescribing metformin for type 2 diabetes.
From the FDA Drug Label
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization
Metformin increases insulin sensitivity by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and increasing peripheral glucose uptake and utilization.
- The exact mechanism of how metformin improves insulin sensitivity is not fully explained in the label, but it is known that insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease 2.
- The dosing recommendations for metformin are not explicitly stated in the provided text, but it does describe the pharmacokinetics and absorption of the drug.
From the Research
Mechanism of Metformin Action
- Metformin increases insulin sensitivity by activating the AMP-activated protein kinase (AMPK) pathway 3, 4, 5.
- AMPK activation leads to increased glucose uptake in skeletal muscle and decreased hepatic glucose production 3, 4.
- Metformin's activation of AMPK is associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity 3.
Dosing Recommendations for Type 2 Diabetes
- The dosing recommendations for metformin in treating type 2 diabetes are not explicitly stated in the provided studies.
- However, the studies suggest that therapeutic doses of metformin can increase AMPK activity in vivo in subjects with type 2 diabetes 3.
Emerging Potential of Metformin Beyond Anti-Hyperglycemic Action
- Metformin has been shown to have diverse effects on the human body, including anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects 6.
- The AMPK pathway has been recognized as responsible for metformin's efficiency and effectiveness in these areas 6.