Metformin

Metforminum

For medical students2 min readUpdated 2026-10-10

Metformin (Metforminum) is an oral antihyperglycemic agent belonging to the biguanide class, used in the management of metabolic disorders. The key pharmacological feature of the drug is that it does not stimulate insulin secretion, but rather enhances tissue sensitivity to insulin.

Dosage Form0.5 g tablets

ClassBiguanides (metabolic regulators)

AdministrationOral, 2–3 times a day with or after meals

Severe Adverse EffectLactic acidosis

Place in the Classification of Antihyperglycemic Agents

To systemize medications used in type 2 diabetes mellitus, they are categorized based on their effect on insulin secretion.

There are endogenous insulin secretagogues (incretion/secretion stimulators), whose action is based on enhancing hormone production by pancreatic $\beta$-cells. These include sulfonylureas, meglitinides, and incretin mimetics (GLP-1 receptor agonists and DPP-4 inhibitors).

Metformin (the primary representative of the biguanide class) differs fundamentally: its hypoglycemic effect is not associated with the stimulation of insulin secretion. Historically, buformin and phenformin were also part of the biguanide class, but they have since been withdrawn from clinical practice. Well-known trade names for metformin include Glucophage, Siofor, and others.

Mechanism of Action

The detailed mechanism of action of metformin is not fully elucidated, but both peripheral and central effects have been proven. Key components include:

Sensitization: Increasing the sensitivity of insulin-dependent tissues to endogenous insulin.
Muscle tissue: Stimulating glucose uptake by skeletal muscles (myocytes).
Liver: Reducing hepatic glucose production (gluconeogenesis and glycogenolysis).
Gastrointestinal tract: Reducing intestinal glucose absorption.
Glucose utilization: Stimulating anaerobic glycolysis.
Hormonal profile: Lowering blood glucagon levels.

Clinical Application and Combination Therapy

Metformin is used in two main therapeutic regimens:

Monotherapy.
Combination therapy. The drug combines exceptionally well with other antihyperglycemic agents to achieve target blood glucose levels.

Common clinical combinations include:

With GLP-1 receptor agonists (e.g., exenatide).
With sulfonylureas.
With DPP-4 inhibitors (gliptins). Fixed-dose combination products exist: Janumet (sitagliptin + metformin) and Galvus Met (vildagliptin + metformin).

Adverse Effects

Although the biguanide class is generally well-tolerated, adverse reactions may occur with metformin use, which are divided into two categories:

1. Dyspeptic symptoms (most common) Includes nausea, vomiting, diarrhea, flatulence, and abdominal pain. Clinical significance: These conditions are not life-threatening to the patient, but they cause discomfort and often limit drug use (reduce compliance).

2. Lactic acidosis (specific and dangerous effect)

Pathogenesis: Directly linked to the drug's mechanism of action. Metformin stimulates anaerobic glycolysis, the end product of which is lactic acid (lactate). Its excessive accumulation leads to a shift in blood pH.
Symptoms: Manifests as weakness, somnolence, myalgia, tachypnea (dyspnea), hypothermia, and bradyarrhythmia. Requires immediate medical attention.

Prescription Rules

According to prescription references, the drug is prescribed in tablet form.

Dosage Form: Tab. 0.5 g.
Dosing Regimen: Oral, 0.5 g 2–3 times a day.
Relation to Food: Take during or after meals (this recommendation helps minimize the risk of dyspeptic disorders).

Mnemonic

Metformin acts like a strict personal trainer: it forces muscles to consume glucose (uptake), prohibits the liver from producing it, shifts cells toward anaerobic metabolism (anaerobic glycolysis -> lactate), and leaves the pancreas alone.

Frequently asked questions

What are the contraindications to prescribing metformin?

Contraindications to metformin include several severe pathological conditions and diseases. These include:

Renal impairment — estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m².
Hepatic impairment.
Acidosis of any etiology — including diabetic ketoacidosis.
Acute coronary syndrome.
Conditions associated with hypoxia — any states accompanied by oxygen deprivation.
Vitamin B12 deficiency anemia.
Alcoholism.
Pregnancy and lactation.

Additionally, the drug must be discontinued 48 hours before and after major surgical procedures or diagnostic studies involving intravascular administration of iodinated radiocontrast agents.

What are the trade names (synonyms) for metformin?

Metformin is available on the pharmacological market under several trade names as monotherapy and fixed-dose combinations. Known synonyms include:

Single-ingredient products — Glucophage, Siofor, and others.
Combination formulations — Janumet (contains sitagliptin and metformin) and Galvus Met (contains vildagliptin and metformin).

Does metformin cause pancreatic beta-cell exhaustion?

No. Unlike sulfonylureas or meglitinides, metformin does not stimulate the secretion of endogenous insulin by beta-cells, but instead enhances tissue sensitivity to insulin.

Why can lactic acidosis develop when taking metformin?

One of the drug's mechanisms of action is the stimulation of anaerobic glycolysis. The end product of this biochemical pathway is lactic acid, the accumulation of which in the body causes acidosis.

What drugs can metformin be rationally combined with?

It is frequently prescribed alongside sulfonylureas, GLP-1 receptor agonists (e.g., exenatide), or DPP-4 inhibitors (sitagliptin, vildagliptin) for comprehensive blood glucose control.

Go deeper

Sulfonylureas and their effect on pancreatic beta-cells.
Incretin mimetics: comparison of GLP-1 agonists (exenatide) and DPP-4 inhibitors (gliptins).
Meglitinides (nateglinide) and mechanisms of postprandial hyperglycemia control.
Alpha-glucosidase inhibitors (acarbose) and intestinal carbohydrate fermentation.
Pathophysiology of lactic acidosis: causes, symptoms, and emergency management.