Metformin

Original Editor - Ashton Randolph

Top Contributors - Lucinda hampton, Ashton Randolph and Aminat Abolade  

Introduction

Metformin is the most widely used drug to treat type 2 diabetes globally. Metformin has been used to treat diabetes since the late 1950s. It is now on the World Health Organisation’s List of Essential Medicines needed for a basic health care system. In Australia, approximately two-thirds of patients with type 2 diabetes are prescribed metformin, either alone or in combination with other pills, or with insulin injections.

• The drug is very safe, is cardioprotective, and enables weight loss.
• Metformin is often used as monotherapy or in combination when diet and exercise are not effective at lowering hyperglycemia.

Action

Metformin reduces blood glucose levels by decreasing glucose production in the liver, decreasing intestinal absorption, and increasing insulin sensitivity. Metformin decreases both basal and postprandial blood glucose.

Metformin is able to reduce glucose production by the liver by approximately one-third, through mechanisms that remain to be fully understood.

Administration

Metformin is an oral medication typically dosed from 500 to 2550 mg per day and administered with a meal to decrease GI upset. The daily dose is often titrated weekly in increments of 500 mg or 850 mg to reduce this risk.

• Recommendations are to take metformin at the same time every day.
• Comes in both immediate-release and extended-release and is available in several combination products with other antidiabetic agents.
• Extended-release tablets are typically taken once daily with an evening meal and should be swallowed with a full glass of water.

Adverse Effects

Metformin is generally regarded as safe and well-tolerated.

• Gastrointestinal side effects, including diarrhea, nausea, and vomiting, are very common and typically occur in up to 30% of patients taking metformin.
• Occurring less frequently, some patients experience chest discomfort, headache, excessive, abnormal sweating, hypoglycemia, weakness, and rhinitis.
• Decreased vitamin B12 levels are associated with long-term metformin and should be monitored, particularly in anemic or peripheral neuropathy patients. Supplementation of vitamin B12 may be necessary

Metformin is associated with a rare but life-threatening condition known as lactic acidosis, where the body builds up too much lactic acid. This can be caused by factors such as heart, liver or kidney failure. There is still controversy over whether metformin is the cause of lactic acidosis or whether it exacerbates the condition.

The consumption of certain items which may increase metformin’s side effect profile. Substances include:

• Alcohol, which increases the risk of lactic acidosis
• The use of amiloride, digoxin, and morphine, because of their competition for elimination pathways
• Cimetidine and furosemide which increase metformin’s effect.

Education

All interprofessional healthcare team members, including clinicians, physiotherapists, nurses, and pharmacists, who look after patients with diabetes mellitus, should be familiar with metformin. Importantly, the drug is relatively cheap. At the same time, the clinicians should encourage patients with diabetes mellitus to discontinue smoking, eat healthily, and participate in regular exercise. While it is a safe and well-tolerated drug, the interprofessional team still needs to monitor its use, be aware of contraindications and interactions

Therapists must educate the patient on

• Monitoring their glucose levels.
• The need to eat before therapy or physical activity, to avoid hypoglycemia.

Potential uses

• 
  It remains controversial as to whether metformin can be used to prevent diabetes as well as treat it. Some clinical trials have shown that metformin is at least as effective as diet and exercise for preventing diabetes in those at high risk of developing it.
• In recent years, metformin, a widely used hypoglycemic drug, has attracted growing attention in the field of anti-aging research. Reportedly, numerous studies have indicated that metformin regulates aging-related pathways, possibly delaying the aging process by modulating these pathways. The elucidation of these anti-aging effects may provide insights into the age-retarding potential of metformin.