Phenformin

Usage

• Phenformin was formerly prescribed for type 2 diabetes mellitus. It is no longer used clinically due to a high risk of lactic acidosis.
• Pharmacological Classification: Biguanide, Antidiabetic Agent.
• Mechanism of Action: Phenformin works by decreasing glucose absorption from the gastrointestinal tract, increasing insulin sensitivity and glucose uptake in tissues, and inhibiting gluconeogenesis in the liver. It requires the presence of insulin to exert its hypoglycemic effect and does not stimulate insulin release. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. It may also impair vitamin B12 absorption.

Alternate Names

• DBI (former brand name)

How It Works

• Pharmacodynamics: Phenformin lowers blood glucose levels primarily by increasing peripheral glucose utilization and decreasing hepatic glucose production. It does not affect insulin secretion.
• Pharmacokinetics: Phenformin is absorbed orally and metabolized in the liver. It is excreted renally.
• Mode of Action: Phenformin activates AMP-activated protein kinase (AMPK), which plays a central role in cellular energy homeostasis. AMPK activation leads to increased glucose uptake and utilization in peripheral tissues and inhibition of hepatic gluconeogenesis.
• Elimination Pathways: Primarily renal excretion.

Dosage

Phenformin is no longer prescribed due to safety concerns. Therefore, dosage information is not applicable. It was previously administered orally, with dosages ranging from 50 to 150 mg per day, divided into two or three doses.

Side Effects

Common Side Effects

• Gastrointestinal disturbances (e.g., anorexia, nausea, vomiting, diarrhea, metallic taste).
• Weight loss.
• Skin reactions.

Rare but Serious Side Effects

• Lactic acidosis (a life-threatening condition).
• Cardiovascular adverse effects.
• Acute pancreatitis.
• Jaundice.

Long-Term Effects

• Vitamin B12 deficiency (due to impaired absorption).

Adverse Drug Reactions (ADR)

• Lactic acidosis is a clinically significant ADR requiring immediate medical intervention.

Contraindications

• Renal impairment.
• Hepatic dysfunction.
• Heart failure.
• Recent myocardial infarction.
• Severe infection.
• Diabetic coma.
• Ketoacidosis.
• Dehydration.
• Pregnancy and breastfeeding.

Drug Interactions

• Cimetidine: May reduce renal clearance of phenformin, increasing the risk of lactic acidosis.
• Alcohol: Increases the risk of lactic acidosis.
• Nephrotoxic drugs: May exacerbate renal impairment and increase the risk of lactic acidosis.
• Numerous other drug interactions exist (see sources).

Pregnancy and Breastfeeding

Phenformin is contraindicated during pregnancy and breastfeeding due to the risk of lactic acidosis in the mother and potential harm to the fetus or infant.

Drug Profile Summary

• Mechanism of Action: Increases insulin sensitivity, decreases glucose absorption and hepatic glucose production.
• Side Effects: GI disturbances, lactic acidosis, cardiovascular events.
• Contraindications: Renal impairment, hepatic dysfunction, heart failure, pregnancy.
• Drug Interactions: Cimetidine, alcohol, nephrotoxic drugs.
• Pregnancy & Breastfeeding: Contraindicated.

Popular Combinations

Phenformin is not used in current clinical practice, therefore, no popular combinations exist.

Precautions

Phenformin is no longer used clinically due to significant safety risks.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Phenformin?

A: Phenformin is no longer used clinically due to the risk of lactic acidosis.

Q2: What are the main side effects of Phenformin?

A: The most common side effects are gastrointestinal issues (nausea, vomiting, diarrhea). The most serious side effect is lactic acidosis, which can be fatal.

Q3: Why was Phenformin withdrawn from the market?

A: Phenformin was withdrawn due to an unacceptably high incidence of lactic acidosis, a serious and potentially fatal metabolic complication.

Q4: What is the mechanism of action of Phenformin?

A: Phenformin works by decreasing glucose absorption, increasing insulin sensitivity, and inhibiting gluconeogenesis in the liver.

Q5: What are the contraindications for Phenformin?

A: Phenformin is contraindicated in patients with renal impairment, hepatic dysfunction, heart failure, and other conditions that increase the risk of lactic acidosis. It is also contraindicated in pregnancy and during breastfeeding.

Q6: Are there any alternative medications to Phenformin?

A: Metformin is a safer biguanide medication used to treat type 2 diabetes. Other classes of antidiabetic drugs are also available, such as sulfonylureas, thiazolidinediones, and GLP-1 receptor agonists.

Q7: How is lactic acidosis treated?

A: Lactic acidosis is a medical emergency and requires intensive supportive therapy. This may include intravenous fluids, sodium bicarbonate to correct acidosis, and measures to improve tissue oxygenation. Hemodialysis may be necessary to remove phenformin and lactate from the circulation.

Q8: Can Phenformin be used in patients with type 1 diabetes?

A: No, phenformin is not effective for type 1 diabetes and is contraindicated in this population.

Q9: What are the symptoms of lactic acidosis?

A: Symptoms can include fatigue, malaise, muscle aches, abdominal pain, nausea, vomiting, rapid breathing, and low blood pressure.