From the Guidelines
No, metformin does not increase insulin resistance; it actually decreases insulin resistance. Metformin is an oral medication commonly prescribed for type 2 diabetes that works by improving the body's sensitivity to insulin, thereby reducing insulin resistance 1. The typical dosage ranges from 500 mg to 2000 mg daily, often divided into two doses with meals. Metformin primarily works in the liver by decreasing glucose production and in muscle tissue by enhancing glucose uptake and utilization. This leads to lower blood sugar levels without causing hypoglycemia when used alone. Metformin also has minimal effect on weight and may even promote modest weight loss in some individuals, which further helps reduce insulin resistance.
Some of the key benefits of metformin include:
- Reducing HbA1c levels by 1.0% to 1.5% versus placebo 1
- Decreasing the likelihood of cardiovascular events and death in obese patients with type 2 diabetes 1
- Being effective, safe, and inexpensive 1
- Having a low risk of hypoglycemia when used alone 1
Common side effects of metformin include gastrointestinal disturbances like diarrhea and nausea, which can often be minimized by starting with a low dose and gradually increasing it, or by taking the medication with food 1. It is also important to note that long-term use of metformin may cause vitamin B12 deficiency, and periodic testing of vitamin B12 levels should be considered in metformin users, especially those with anemia or peripheral neuropathy 1.
Overall, metformin is a well-established and effective treatment for type 2 diabetes, and its benefits in reducing insulin resistance and improving glycemic control make it a valuable medication for patients with this condition.
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 decreases insulin resistance by improving insulin sensitivity. It does this by increasing peripheral glucose uptake and utilization, which in turn lowers blood glucose levels.
- Key points:
- Metformin improves insulin sensitivity
- Metformin decreases hepatic glucose production
- Metformin decreases intestinal absorption of glucose
- Metformin increases peripheral glucose uptake and utilization 2
From the Research
Metformin and Insulin Resistance
- Metformin is known to counter insulin resistance and offer benefits against many features of the insulin resistance syndrome (Syndrome X) 3.
- It improves hepatic and peripheral sensitivity to insulin, with both direct and indirect effects on liver and muscle 4.
- Metformin reduces insulin resistance and decreases blood glucose concentration by inhibiting gluconeogenesis and suppressing hepatic glucose production with improved peripheral tissue insulin sensitivity 5.
- The drug's mechanism of action is based on reducing glucose production in the liver, decreasing insulin resistance, and increasing insulin sensitivity 6.
Effects of Metformin on Insulin Signaling
- Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways 4.
- It also activates AMPK, which is involved in glucose uptake and insulin signaling 7.
- However, metformin-induced activation of AMPK does not seem to improve peripheral insulin resistance, suggesting that other mechanisms may be involved in its effects on insulin signaling 7.
Overall Effects of Metformin
- Metformin does not increase insulin secretion or cause serious hypoglycaemia, unlike other antidiabetic medications 3.
- It has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 6.
- Metformin's effects on insulin resistance and insulin signaling contribute to its overall efficacy in managing type 2 diabetes 4, 5, 6.