The Possible Benefits of Metformin for Type 2 Diabetes and Other Health Conditions

What Is Metformin?

Metformin is a biguanide class molecule used effectively to treat diabetes in more than 120 million people worldwide. It is commonly used to treat the anti-aging crowd as some animal models have shown facts of an increased life span and health. The complete mechanism of action is not fully clear but it is known to activate the enzyme AMPK which suppresses glucose production in the liver and that increases insulin-mediated glucose uptake which is key in helping treat diabetes. Metformin contains an active ingredient that is 500mg of metformin hydrochloride. It also contains carboxyl methyl cellulose, citric acid monohydrate, and magnesium stearate.

How Does Metformin Work – Mode of Action

Metformin is an oral anti-diabetic drug whose mechanism of action is still not known clearly. Metformin does not bind to plasma protein. It is excreted out unchanged in the urine and hence it is contraindicated in renal failure. However, the primary effect of metformin is to activate the enzyme adenosine monophosphate-activated protein kinase (AMPK) in the liver which inhibits gluconeogenesis. This inhibition leads to a decrease in glucose production. Patient with type 2 diabetes has less fasting glycemia as well as lower post-prandial hyperglycemia after a metformin administration. Hypoglycemia is rare during metformin therapy; hence it is called a euglycemic agent.

Other mechanisms of metformin include −

• Increases insulin sensitivity.

• Increases fatty acid oxidation.

• Decrease intestinal glucose absorption.

• It also delays gastric emptying and reduces appetite which results in weight loss in some cases.

Benefits of Metformin in Treating Diabetes Type 2 And Its Complications

Metformin is the most prescribed drug for type 2 diabetes which is known as vitamin M. It is prescribed for people with type 2 diabetes and prediabetes if they cannot control their blood sugars well enough through diet and exercise alone. Metformin pills lower the blood sugar levels by reducing the amount of glucose produced by the liver and making the cells more sensitive to insulin. Thus metformin also improves insulin sensitivity which helps the body use glucose for energy.

Metformin does not cause weight loss but can help obese people to lose weight as part of a healthy lifestyle program that includes diet and exercise. It also reduces the amount of glucose released from the stomach into the intestine as a result it slows down how quickly the food empties from the stomach into the intestines so that blood sugar level lowers after you eat.

Metformin use is not helpful and is avoided in patients with liver or kidney problems and even in a condition called acidosis. Other medications may interfere with the drug’s ability to work and add to the risk of side effects.

When and How to Use Metformin in The Treatment of Type 2 Diabetes

Initially, as a first line of treatment lifestyle modification should be done with a special emphasis on diet and exercise. But when we fail to manage diabetes alone, metformin provides us a good helping hand to reduce our blood sugar levels. It may be prescribed to those diagnosed with prediabetes or those at higher risk of developing diabetes. Metformin is recommended as a first line of treatment for type 2 diabetes due to many reasons.

• It reduces the risk of developing heart disease and stroke.

• It reduces the risk of developing kidney disease, blindness, and nerve damage.

Metformin works at its best when combined with other modifications in lifestyle such as diet, exercise, and weight loss. There are no initial standard guidelines on how much metformin to be prescribed, as it depends on a person’s weight, blood sugar levels, and how well one responds to the medication. An endocrinologist is the right person to take a call.

What Are the Clinical Uses of Metformin?

A few of Metformin’s clinical uses are given below −

• Metformin is the drug of choice in the treatment and prophylaxis of type 2 diabetes mellitus. Here it is used as monotherapy or in combination with other oral hyperglycemic agents as a combination therapy.

• Metformin is used in PCOD to decrease insulin resistance and improve ovulation.

• It is also used in metabolic syndrome in HIV, non-alcoholic fatty liver disease, and to reduce antipsychotics-associated weight gain.

• Metformin may be helpful in decreasing blood cholesterol levels.

• It prevents kidney damage and helps with weight loss.

• Metformin use is associated with decreased risk of pancreatic cancer in diabetes mellitus.

• It also decreases the risk of macrovascular and microvascular diseases.

• It is currently under trial as an anti-aging agent. One interesting fact is that metformin did not prevent diabetes in older, leaner pre-diabetics.

Metformin Side-effects

The side effects and some toxicities of metformin are discussed below.

• It causes the most common side effects like nausea, vomiting, diarrhea, and anorexia. These effects can be avoided by taking low doses of metformin and by taking it with a meal.

• Sometimes insomnia is observed with metformin use.

• Long-term use of metformin can cause vitamin B12 deficiency. Metformin interferes with the calcium-dependent absorption of vitamin B12 intrinsic factor complex in the terminal ileum.

Periodic screening of vitamin B12 should be considered especially in patients with peripheral neuropathy or macrocytic anemia. Increased intake of calcium may prevent metformin induced vitamin B12 deficiency.

• Lactic acidosis more commonly occurs in renal failure patients as it is excreted unchanged in the urine. So in renal failure patients, the excretion of metformin is decreased and hence the levels increase in the blood. Primary action of metformin is blocking hepatic gluconeogenesis, where the main substrate is lactate glycerol alanine which is converted into glucose in the liver.

So increased metformin levels in the blood in renal failure patients impair the hepatic utilization of lactic acid. This increases the lactic acid in the blood which eventually leads to lactic acidosis. Other conditions which increase the chances of lactic acidosis where metformin is contra-indicated are −

• Severe respiratory disease.

• Liver disease.

• Congestive heart failure.

• Chronic alcohol abuse.

Role of Metformin - Research and Studies

This study is limited to adults aged 70-90. Of the total 1037 participants, 914 have no diabetes and 123 have diabetes in which they have received metformin. All the adults were followed over the course of 6 years with various tests on cognition, executive functioning, memory, etc. Metformin is administered every 2 years. So all three of the following groups are examined.

• No diabetes.

• Diabetes plus metformin.

• Diabetes without metformin.

Here the key of this study is to know how the diabetes plus metformin group performed in comparison to the other 2 groups and to know the better cognition performance when compared to the diabetes group without metformin. As diabetes is associated with a cognitive deficit and dementia about 60% of the people affected with type 2 diabetes developed dementia. If the diabetes group with metformin shows the same cognitive performance as the group without diabetes, then it shows a significant result and was seen success with this study. The percentage of those with dementia was also known through this study.

• 8.2% of dementia is seen among people with no diabetes.

• 6% of dementia is seen among the diabetes group with metformin.

• 14.5% of dementia is seen in the diabetes without metformin group.

Statistical analysis showed that metformin use was associated with an 81% reduction in dementia risk. So overall it is another encouraging study of the metformin benefits.

Summary

Metformin is the most prescribed anti-diabetic drug which belongs to the biguanide class of drugs. This is the only drug among the biguanide class and the other previously known drug phenformin is discontinued as it is known to cause lactic acidosis. Type 2 diabetes is a chronic condition that affects the way body processes glucose or sugars. As this disease is mostly characterized by insulin resistance and impaired insulin secretion, metformin here plays a role in lowering blood sugar levels by decreasing the amount of glucose produced in the liver and rising the insulin sensitivity in the muscle, fat, and liver cells. Metformin has very limited side effects which can be ignored looking at its benefits.