How Genes Influence The Breakdown Of Metformin?

What Is Metformin?

Metformin is an oral prescription drug used to control blood sugar levels in diabetic patients.

It is usually used along with diet and exercise to help blood sugar control.

In some people, metformin may be used with insulin or other medications in type 2 diabetes.

However, metformin is not used in patients with Type 1 diabetes (juvenile diabetes)

Metformin is available in two oral forms– tablet and solution. Some physicians may prescribe metformin to treat PCOS or Polycystic ovary Syndrome.

Metformin is available in two forms:

Immediate release
Extended-release

What Is Metformin Used For?

Metformin is an oral drug used to treat high blood sugar levels in patients with type 2 diabetes.

They are often the first line of treatment and used in combination with diet and exercise.

In some people, metformin may be used with insulin or other antidiabetic drugs as combination therapy.

Do Doctors No Longer Prescribe Metformin?

After a report in May 2020 about extended-release metformin tablets containing unacceptable levels of a probable carcinogen (cancer-causing substance), the FDA recommended some makers of metformin take their products off the US market.

During this time, many doctors stopped prescribing metformin and switched to alternatives.

How Does Metformin Work?

Metformin belongs to the biguanide class of drugs.

It acts in the following three ways to lower blood sugar levels in people with diabetes:

Reduces the glucose made by the liver
Decreases the amount of glucose absorbed by the body
Increases the effect of the hormone insulin (responsible for removing excess sugar from your blood) on your body

How Long Does It Take For Metformin To Work?

You will begin to notice the effects of metformin on your body within 48 hours of taking the drug.

It can take around four to five days to experience the full effect of metformin.

The time taken by metformin to show effects on the body also depends upon the dosage of the drug taken.

How Long Does It Take For Metformin To Regulate Periods?

Though metformin is an antidiabetic drug, it may be used to regulate the menstrual cycle in women with PCOS.

Metformin regularizes the menstrual cycle, reduces the Body Mass Index(BMI), and treats the signs of PCOS within six months of treatment.

When To Switch From Metformin To Insulin?

The decision to switch from metformin to insulin is usually well-evaluated and taken by your physician.

Your doctor may switch you to insulin if your blood sugar levels are still high or metformin cannot control your type 2 diabetes.

Side Effects Of Metformin

Though metformin is a safe drug, it may cause side effects in some people.

Some commonly observed side effects of metformin include:

Nausea
Diarrhea
Heartburn
Gas
Low blood sugar levels

If these symptoms do not go away in a few days, you must inform your doctor about the same.

If you experience any of the following serious side effects of metformin, visit your doctor immediately:

Unusual pain in the muscles
Breathing trouble
Pain in the stomach
Vomiting
Irregular or slow heart rate
Lightheadedness
Confusion
Low energy levels

Does Metformin Cause Hair Loss?

There is no conclusive proof that metformin causes hair loss.

However, a 2016 study states that long-term use of metformin may cause vitamin B12 deficiency and anemia, and hair loss is a symptom of both these conditions.

Does Metformin Cause Erectile Dysfunction (ED)?

According to a 2016 study, metformin results in a significant reduction in testosterone levels, which causes low sex drive and erectile dysfunction.

Is Metformin Bad For Your Kidneys?

Metformin does not cause kidney damage.

However, metformin may have an adverse effect on the renal function of people with type 2 diabetes and moderate chronic kidney disease.

Can Metformin Cause Pancreatitis?

Drugs cause around 2% of pancreatitis cases; metformin therapy is not one of them.

Does Metformin Raise Blood Pressure?

Metformin does not have any effect on an individual’s blood pressure.

Interactions With Other Drugs

Metformin may interact with other drugs.

Drug interactions may give rise to adverse effects or reduce the expected effect of metformin.

Some significant drug interactions of metformin include:

Metformin and Other Diabetes Drugs

If you take other anti-diabetic medications like insulin or glyburide, taking metformin may cause low blood sugar levels.

Metformin and Diuretics

Diuretics, also called water pills, are routinely used to lower blood pressure levels in hypertensive patients.

Taking diuretics like furosemide and hydrochlorothiazide with metformin can reduce blood sugar-lowering effects.

Metformin and Nifedipine

Nifedipine is a calcium channel blocker used to lower and maintain optimum blood pressure levels in hypertensive patients.

Nifedipine may increase metformin levels when taken together, which may increase your risk of metformin side effects.

Metformin and Nicotinic Acid (cholesterol-lowering drug)

Nicotinic acid is a cholesterol-lowering drug.

Taking it with metformin may reduce metformin’s blood sugar-lowering effects.

Metformin and Glaucoma Drugs

Drugs like acetazolamide, brinzolamide, dorzolamide and methazolamide are used in treating glaucoma.

Taking any of these with metformin may increase your risk of lactic acidosis.

Metformin and Topiramate

Topiramate is used to treat seizures and nerve pain.

Taking it with metformin may increase your risk for lactic acidosis.

Metformin and Phenytoin

Phenytoin is routinely used in treating seizures.

Taking it with metformin reduces metformin’s blood sugar-lowering effects and may lead to a rise in blood sugar levels.

Metformin and Cimetidine

Cimetidine is used to treat heartburn and acidity-related issues.

Taking it with metformin may increase your risk for lactic acidosis.

Other drugs like hormonal pills, isoniazid (anti-tubercular drug), phenothiazines (antipsychotic drugs), and thyroid medications may interact with metformin to lower its effects on blood sugar levels.

So, always inform your doctor if you take any of these drugs before taking metformin.

Can I Take Imodium With Metformin?

Diarrhea, vomiting, and nausea may be seen in some people taking metformin. Imodium is an anti-diarrheal drug and can be safely taken with metformin.

Can You Take Glipizide And Metformin Together?

Glipizide, like metformin, is an anti-diabetic drug.

Taking these two drugs together may increase your risk for hypoglycemia or low blood sugar.

Hence, it is recommended that you avoid this combination.

Metformin: Gene-Drug Interactions

The SLC22A1 Gene

Solute carrier Family 22 member 1or SLC22A1 is a gene present on chromosome 17 and associated with diseases like leukemia.

This gene participates in the transport of sugars like glucose, bile salts, organic acids, metal ions, and amine compounds.

rs12208357 is a single nucleotide polymorphism or SNP in the SLC22A1 gene.

Individuals with the CC and CT genotype of this SNP may have an increased bioavailability (the portion of the drug consumed that enters the body's circulation to bring about the desired effect) of metformin compared to those having the TT genotype.

rs72552763 is another SNP in the SLC22A1 gene.

In diabetic individuals with the GAT/del genotype, the lowest concentration of metformin in the bloodstream is lesser than those with the GAT/GAT genotype.

Individuals treated with metformin having GAT/GAT genotype may have a higher trough of metformin than those with GAT/del genotype.

The SLC47A1 Gene

Solute carrier family 47 member 1 or SLC47A1 is located on chromosome 17 and plays a role in transporting sugars, glucose, bile salts, organic acids, metal ions, and amine compounds in the body.

rs2289669 is an SNP in the SLC47A1 gene.

Diabetic individuals with the AA genotype may have an increased response to metformin than AG and GG genotypes.

Recommendations To Use Metformin

Medical history

Tell your doctor if you have any medical condition like kidney disease, history of heart attack, stroke, diabetic ketoacidosis, heart or liver condition.

Metformin may not be the right choice of medication in people with a few medical conditions, including the ones mentioned above.

Current medications

To avoid adverse drug interactions, it is advisable that you inform your doctor about all prescription and non-prescription drugs and supplements that you may be taking.

Menstruation, pregnancy, and breastfeeding

Metformin may cause changes in your menstrual cycle and promote ovulation. This increases your chances of becoming pregnant.

If you are pregnant or plan to conceive, inform your doctor about the same.

Metformin is given during pregnancy only after evaluating the benefits vs. risks.

Metformin may pass into breast milk.

So, you must inform your doctor if you are breastfeeding before taking the drug.

What Should I Avoid While Taking Metformin?

It is recommended to avoid alcohol while taking metformin as it may increase your risk for lactic acidosis.

Can You Drink Alcohol While Taking Metformin?

Drinking alcohol while taking metformin may increase your risk for lactic acidosis and, therefore, must be avoided.

Does Metformin Expire?

It is best to take metformin within the expiry date printed on the box or file.

Can You Take Metformin On An Empty Stomach?

Metformin is ideally taken with food.

While it is okay to take it on an empty stomach, having it with a meal reduces the risk of stomach upset.

Genetic testing

Genetic testing may help your doctor understand how your body may react to metformin.

In people with certain genotypes, your doctor may prescribe an alternate drug if they feel metformin may not bring about the desired effects.

Analyze Your Genetic Response to Metformin

Summary

Metformin is an oral, anti-diabetic prescription drug used to lower blood sugar levels in type 2 diabetes patients.
Metformin acts on the liver to reduce glucose production, reduce the body's glucose absorption, and increase insulin’s effectiveness.
Though largely safe, metformin may cause side effects in some people.
Since metformin interacts with a few drugs, it is best to inform your doctor about all medications you are currently taking.
Polymorphisms in two genes– SLC22A1 and SLC47A1, are studied to understand how metformin affects blood sugar levels.
To ensure the safe use of metformin, inform your doctor about your medical history and all medicines and supplements you take.