From the Guidelines
Metformin lowers blood glucose by improving insulin sensitivity, reducing glucose absorption, and decreasing hepatic glucose production, making it a commonly used and effective medication for type 2 diabetes management, as supported by the most recent evidence from 2025 1.
Mechanism of Action
The exact mechanism of how metformin lowers blood glucose is complex and involves multiple pathways. However, it is known to:
- Improve insulin sensitivity, allowing glucose to enter cells more effectively
- Reduce glucose absorption from the gastrointestinal tract
- Decrease hepatic glucose production, which contributes to high blood glucose levels in type 2 diabetes
Clinical Evidence
The 2025 standards of care in diabetes published in Diabetes Care 1 emphasize metformin as a first-line treatment for type 2 diabetes due to its efficacy, safety, and cost-effectiveness. It is also noted for its benefits in reducing microvascular complications, cardiovascular events, and death.
Key Considerations
When prescribing metformin, it's essential to consider the potential side effects, such as gastrointestinal intolerance, and the need for gradual dose titration or the use of an extended-release formulation. Additionally, metformin may be safely used in people with an estimated glomerular filtration rate ≥30 mL/min/1.73 m², but caution is advised in those with renal impairment.
Comparison with Other Treatments
Metformin has been compared to other glucose-lowering agents, such as sulfonylureas and DPP-4 inhibitors, and has been found to have beneficial effects on A1C, weight, and cardiovascular mortality 1. However, the choice of medication should be individualized based on patient preferences, needs, and values.
Conclusion is not allowed, so the answer will be ended here.
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 hydrochloride tablets help control your blood sugar in a number of ways. These include helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb.
Metformin lowers blood glucose by:
- Decreasing hepatic glucose production
- Decreasing intestinal absorption of glucose
- Improving insulin sensitivity by increasing peripheral glucose uptake and utilization 2
From the Research
Mechanism of Action
- Metformin lowers blood glucose concentration by mechanisms different from those of insulin secretagogues, such as sulphonylureas, or exogenous insulin therapy 3.
- It acts by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output 3, 4.
- By reducing hepatic glucose output, metformin lowers blood glucose and insulin levels with minimal risk of hypoglycaemia 3.
Effects on Blood Glucose Levels
- Metformin has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 4.
- When used as monotherapy, metformin can lower HbA1c by around 1.5% 3.
- The improved glucose control seen with metformin is achieved without weight gain 3.
Comparison with Other Therapies
- Metformin is considered a first-line choice for the management of type 2 diabetes 3, 5.
- Newer agents, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, are favored as the first-line therapy in individuals with type 2 diabetes who would benefit from cardio-renal protection 4.
- Combination therapy with insulin and oral antidiabetic agents, including metformin, can safely establish excellent glycemic control in most patients 6.