Metformin
Derived from the French lilac, Metformin has been in use since the 1950s to manage type 2 diabetes. It has risen in prominence due to its efficacy, safety, and affordability.
FDA Indications
- Type 2 Diabetes Mellitus: Metformin is FDA-approved for the management of high blood sugar in conjunction with diet and exercise for adults and children aged 10 and above. (FDA Label)
Mechanism of Action
-
For Diabetes: Metformin primarily works by inhibiting hepatic gluconeogenesis—the liver's production of glucose. It also improves insulin sensitivity in muscles and fat cells, and it decreases the absorption of glucose from the gastrointestinal tract.
-
For Weight Loss: Metformin assists in weight loss by reducing insulin resistance, which can lower the body's fat storage. It also has an appetite-suppressing effect, making it easier to control caloric intake.
-
For Longevity: Theories propose that Metformin may extend lifespan by mimicking aspects of calorie restriction, primarily through the activation of AMP-activated protein kinase (AMPK). AMPK is a master regulator of cellular energy homeostasis, which influences metabolism and inflammation.
Off-Label Uses
-
Weight Loss and Metabolic Health: The drug can assist in weight loss by enhancing insulin sensitivity, thus lowering circulating glucose levels, and by suppressing appetite.
-
Longevity: Metformin has been the subject of research for its potential to extend lifespan and improve aspects of health in aging, although this is still an active area of investigation.
Clinical Evidence
-
For Diabetes: The Diabetes Control and Complications Trial (DCCT) showed that Metformin could lower HbA1c levels by an average of 1.5%, thereby reducing complications. (NEJM)
-
For Weight Loss: Studies have shown weight loss ranging from 5-7% body weight over a one-year period when using Metformin.
-
For Longevity: There is ongoing debate about Metformin's potential for lifespan extension. Some animal studies have suggested an increase in lifespan by about 5%. Research in this area is ongoing.
Side Effects
- Common: Diarrhea, nausea, abdominal pain
- Rare but Serious: Lactic acidosis, a potentially fatal metabolic condition
- Special Concern: Metformin may deplete Vitamin B12 levels, requiring supplementation.
Drug Interactions
-
Alcohol, insulin, or other diabetes medications may increase the risk of lactic acidosis.
-
Use caution with contrast dyes often used in certain radiology procedures; temporary discontinuation of Metformin may be advised.
Contraindications
- Chronic kidney disease (CKD)
- Severe liver disease
- History of lactic acidosis
- Hypersensitivity to Metformin
Warnings and Precautions
- Risk of lactic acidosis, especially in those with kidney problems
- Vitamin B12 deficiency may occur and should be monitored
- Not recommended during pregnancy
