The Predominant Effect of Metformin
The predominant effect of metformin is to decrease excess amounts of glucose produced by the liver, which impacts the fasting blood glucose levels. 1, 2, 3
Primary Mechanism of Action
Metformin's major therapeutic effect is suppression of hepatic glucose production (HGP), particularly by inhibiting hepatic gluconeogenesis 1, 3. The FDA drug label explicitly states that "metformin decreases hepatic glucose production" as its primary mechanism 3. This hepatic effect is what primarily lowers fasting glycemia in patients with type 2 diabetes 1, 2.
Why the Other Options Are Incorrect:
Glucose absorption from the gut: While the FDA label mentions that metformin "decreases intestinal absorption of glucose," this is a secondary effect and not the predominant mechanism 3. The primary therapeutic benefit comes from hepatic suppression 1, 2.
Urinary glucose excretion: This is completely incorrect for metformin. This mechanism describes SGLT-2 inhibitors, not metformin 1. Metformin does not increase glucose excretion in urine 3.
Appetite suppression: While metformin may cause gastrointestinal side effects including reduced appetite, this is an adverse effect rather than a therapeutic mechanism 2, 4. The glucose-lowering effect occurs independently of appetite changes 1.
Complete Mechanism Profile
Beyond hepatic glucose suppression, metformin has additional mechanisms that contribute to its overall effect:
- Improved peripheral insulin sensitivity: Metformin increases peripheral glucose uptake and utilization in muscle and adipose tissue 3, 5
- No effect on insulin secretion: Critically, insulin secretion remains unchanged with metformin therapy, distinguishing it from sulfonylureas 2, 3
- Weight neutrality or modest weight loss: Unlike many glucose-lowering medications, metformin does not cause weight gain 1, 2
Clinical Efficacy
Metformin typically reduces HbA1c by 1.0-1.5 percentage points when used as monotherapy 1, 2. This glucose-lowering effect is achieved primarily through the reduction in hepatic glucose output, which directly impacts fasting blood glucose levels 1, 2.
Key Clinical Pitfall
The most important distinction is that metformin does not cause hypoglycemia when used alone because it does not increase insulin secretion 2, 6. Hypoglycemia only becomes a risk when metformin is combined with insulin or insulin secretagogues like sulfonylureas 1, 2.