From the Guidelines
Metformin is the most effective and crucial medication for diabetics due to its ability to decrease hepatic glucose production, increase peripheral insulin sensitivity, and reduce hyperglycemia, ultimately leading to improved morbidity, mortality, and quality of life outcomes. Metformin works by reducing glucose production in the liver, improving insulin sensitivity in muscle and fat cells, and decreasing intestinal absorption of glucose. It's crucial for diabetics because it effectively lowers blood sugar without causing hypoglycemia when used alone, helps with weight management, and has cardiovascular benefits 1.
The benefits of metformin are well-documented, including a 32% reduction in microvascular and macrovascular diabetes-related outcomes, a 39% reduction in MI, and a 36% reduction in all-cause mortality rate, as seen in the UKPDS study 1. Additionally, metformin has been shown to have a beneficial effect on HbA1c, weight, and improved ASCVD outcomes compared to sulfonylureas, with an acceptable safety profile and low cost 1.
Some key points to consider when prescribing metformin include:
- Starting with a low dose, such as 500 mg once or twice daily with meals, and potentially increasing to a maximum of 2000-2550 mg daily divided into two or three doses 1
- Monitoring for gastrointestinal side effects, such as diarrhea and nausea, which can be minimized by starting with a low dose and taking it with food 1
- Considering the risk of lactic acidosis, particularly in patients with CKD, and using caution when prescribing metformin to these patients 1
- Recognizing the importance of metformin as the first-line medication for type 2 diabetes due to its proven safety record, effectiveness, and additional benefits such as modest weight loss and reduced risk of cardiovascular events 1
Overall, metformin is the recommended first-line treatment for type 2 diabetes, unless contraindicated, due to its effectiveness, safety, and additional benefits, as supported by high-quality evidence from recent studies 1.
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 With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
Metformin works by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity. It is important for diabetics because it helps lower blood glucose levels and improve glucose tolerance. The exact mechanisms of metformin are:
- Decreasing hepatic glucose production
- Decreasing intestinal absorption of glucose
- Improving insulin sensitivity by increasing peripheral glucose uptake and utilization Metformin therapy does not change insulin secretion, but may decrease fasting insulin levels and day-long plasma insulin response 2.
From the Research
Mechanism of Action
- Metformin reduces glucose levels by decreasing hepatic glucose production, reducing intestinal glucose absorption, and increasing insulin sensitivity 3, 4, 5
- It does not stimulate insulin secretion, which can help prevent hypoglycemia and weight gain 4
Importance for Diabetics
- Metformin is the most prescribed oral antidiabetic worldwide and is often used as a first-line treatment for type 2 diabetes mellitus 3
- It can be used as monotherapy or combined with other antidiabetics, such as sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin, to improve its efficacy 3, 4, 6
- Metformin has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 5
Benefits and Risks
- Metformin has beneficial effects on serum lipid profiles and can help with weight control 4
- However, prolonged usage of metformin may lead to abdominal discomfort, deficiency of Vitamin B12, or lactic acidosis 3
- The risk of lactic acidosis is minimal if contraindications, particularly renal impairment, and prescribing guidelines are respected 4
- Recent studies have explored additional benefits of metformin in polycystic ovarian disease, gestational diabetes mellitus, cognitive disorders, and immunological diseases, but more extensive studies are needed to confirm these benefits 3
Comparison with Other Treatments
- Metformin-sulfonylurea combination therapy may be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy 4
- However, sulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with other oral antihyperglycemic agents 7
- DPP-4 inhibitors plus metformin may be associated with significantly lower risks of major adverse cardiovascular events and all-cause mortality compared to sulfonylureas plus metformin 6