Which organs are responsible for eliminating metformin, and why is the drug contraindicated in their pathology?

Sources do not specify the exact organs responsible for metformin excretion. In the presence of hepatic and renal dysfunction, the drug is contraindicated due to the risk of accumulation and lactic acidosis.

How do biguanides lower blood sugar if they do not stimulate insulin production?

The hypoglycemic effect is achieved by increasing tissue sensitivity to endogenous insulin, stimulating glucose uptake by skeletal muscle, reducing hepatic glucose production, and decreasing intestinal absorption.

Why is metformin considered the drug of choice for type 2 diabetes in obese patients?

In addition to effective glucose control, metformin systemically affects eating behavior—it suppresses appetite and promotes weight loss. Additionally, it improves the lipid profile by lowering cholesterol, triglycerides, and atherogenic LDL.

What is the mechanism of lactic acidosis development during metformin therapy?

The pathogenesis of this dangerous complication is driven by the drug's active stimulation of anaerobic glycolysis. Lactic acid is the end product of this biochemical pathway, and its excessive accumulation in the blood leads to severe acidosis.

Why is metformin strictly contraindicated in renal or hepatic disease?

Impairment of these organs slows down drug excretion and leads to its accumulation (cumulation) in the body. This critically increases the risk of lactic acidosis, which is accompanied by weakness, hypothermia, dyspnea, and bradyarrhythmia.

Home › Pharmacology › Biguanides

Biguanides

*Metforminum*

For medical students2 min readUpdated 2026-10-10

Biguanides are a class of oral hypoglycemic agents used in endocrinology. Today, the primary and only approved representative of this class is metformin (known under brand names such as Glucophage, Siofor, etc.). Historically, buformin and phenformin were also part of this group, but they have been completely withdrawn from clinical practice. The fundamental feature of biguanides is that their blood glucose-lowering effect is not mediated by stimulating insulin secretion from pancreatic $\beta$-cells.

Primary agentMetformin. Buformin and phenformin are withdrawn from clinical practice.

Key distinctionDoes not stimulate insulin secretion by pancreatic beta-cells.

Action in skeletal muscleStimulates active glucose uptake by skeletal muscle.

Severe complicationLactic acidosis due to excessive stimulation of anaerobic glycolysis.

Lipid metabolismReduces atherogenic LDL, total cholesterol, and triglycerides.

Mechanism of Action of Metformin

Although the detailed molecular mechanism of metformin is not fully elucidated, pharmacologists distinguish several proven components, including both peripheral and central effects.

Tissue Sensitization: The drug significantly increases the sensitivity of insulin-dependent tissues to endogenous insulin.
Skeletal Muscles: Active stimulation of glucose uptake by myocytes occurs.
Liver: Metformin suppresses hepatic gluconeogenesis (glucose production by hepatocytes).
Gastrointestinal Tract: Intestinal glucose absorption is reliably reduced.
Glucose Utilization: Anaerobic glycolysis is stimulated at the cellular level.
Hormonal Profile: A decrease in systemic glucagon levels is observed.

Metabolic Effects and Indications

Biguanides exert complex metabolic effects that extend beyond simple glycemic control. Of particular importance is their impact on the lipid profile: therapy with metformin is associated with reduced levels of atherogenic low-density lipoproteins (LDL), as well as a decrease in plasma total cholesterol (TC) and triglycerides (TG).

Equally important is the drug's effect on eating behavior—it helps suppress appetite, which naturally leads to weight loss.

Due to the combination of hypoglycemic action and weight reduction, type 2 diabetes mellitus is the primary indication for prescribing biguanides. Furthermore, metformin is recognized as the drug of choice for patients with diabetes who are overweight or obese.

Adverse Effects

Adverse reactions to metformin fall into two main categories:

Dyspeptic symptoms: These are the most frequent side effects. Patients often complain of nausea, vomiting, diarrhea, marked flatulence, and abdominal pain. Although not life-threatening, these symptoms cause significant discomfort and frequently limit drug use.
Lactic acidosis: A specific and highly dangerous adverse effect. Its pathogenesis is inextricably linked to the mechanism of action of biguanides: because metformin stimulates anaerobic glycolysis, the end product of this pathway—lactic acid—begins to accumulate in excess. The clinical presentation of lactic acidosis includes progressive weakness, somnolence, severe myalgia, tachypnea/dyspnea, hypothermia, and bradyarrhythmia.

Contraindications

Given its pharmacodynamics and the risk of severe complications, biguanides have a strict list of contraindications. The drug must not be prescribed in cases of:

Hypersensitivity to the active substance.
Hepatic and renal impairment. Decreased function of these organs creates a high risk of drug accumulation (cumulation), which substantially increases the likelihood of lactic acidosis.
Metabolic acidosis of any etiology.
Pregnancy and lactation (breastfeeding).

Mnemonic

To quickly remember the profile of metformin, use the three "S" rule: Sensitizes tissues to endogenous insulin, Suppresses appetite and body weight, Stimulates anaerobic glycolysis (which explains the risk of lactic acidosis).

Frequently asked questions

Which organs are responsible for eliminating metformin, and why is the drug contraindicated in their pathology?: Sources do not specify the exact organs responsible for metformin excretion. In the presence of hepatic and renal dysfunction, the drug is contraindicated due to the risk of accumulation and lactic acidosis.
How do biguanides lower blood sugar if they do not stimulate insulin production?: The hypoglycemic effect is achieved by increasing tissue sensitivity to endogenous insulin, stimulating glucose uptake by skeletal muscle, reducing hepatic glucose production, and decreasing intestinal absorption.
Why is metformin considered the drug of choice for type 2 diabetes in obese patients?: In addition to effective glucose control, metformin systemically affects eating behavior—it suppresses appetite and promotes weight loss. Additionally, it improves the lipid profile by lowering cholesterol, triglycerides, and atherogenic LDL.
What is the mechanism of lactic acidosis development during metformin therapy?: The pathogenesis of this dangerous complication is driven by the drug's active stimulation of anaerobic glycolysis. Lactic acid is the end product of this biochemical pathway, and its excessive accumulation in the blood leads to severe acidosis.
Why is metformin strictly contraindicated in renal or hepatic disease?: Impairment of these organs slows down drug excretion and leads to its accumulation (cumulation) in the body. This critically increases the risk of lactic acidosis, which is accompanied by weakness, hypothermia, dyspnea, and bradyarrhythmia.

Go deeper

Central and peripheral cellular mechanisms of action of metformin
Pathogenesis of lactic acidosis: biochemistry of anaerobic glycolysis and lactic acid accumulation
Effects of biguanides on the lipid profile: mechanisms of LDL and triglyceride reduction
Reasons for the withdrawal of buformin and phenformin from modern clinical practice
Pharmacokinetics of metformin and mechanisms of its accumulation in renal and hepatic pathologies