Metformin is one of the most prescribed medications worldwide, primarily used to manage type 2 diabetes.

Known for its effectiveness in controlling (low) blood sugar levels, it has become a cornerstone in diabetes treatment plans. Its benefits extend beyond blood sugar control, with emerging research suggesting potential roles in weight management, polycystic ovary syndrome (PCOS), and even anti-aging.

Despite its widespread use and efficacy, metformin is not without side effects. Many patients experience these side effects, ranging from mild digestive issues to more severe complications, which can impact their quality of life or adherence to the medication. The severity can vary greatly among individuals based on dosage, duration of treatment, and personal health factors.

Understanding the side effects of metformin is crucial for anyone taking the medication. It allows patients to make informed decisions about their health, recognize warning signs, and work with healthcare providers to optimize treatment.

Let’s explore a comprehensive overview of metformin, its mechanism of action, and a detailed breakdown of common side effects to help you better understand this widely used medication.

What is Metformin and How Does It Work?

Metformin is an oral medication belonging to the class of drugs called biguanides. It was first introduced in the 1950s and gained FDA approval for managing diabetes in the United States in 1995.

Today, it is considered a first-line therapy for type 2 diabetes and is often prescribed alongside lifestyle modifications such as diet and exercise. In addition to its role in treating diabetes, metformin has been found to have other therapeutic applications.

For instance, it is frequently used off-label to manage PCOS, a condition characterized by hormonal imbalances and insulin resistance. Moreover, emerging studies suggest metformin may have the potential to reduce the risk of certain cancers, slow aging, and improve cardiovascular outcomes.

How Metformin Works in the Body

Metformin is a widely used medication for managing type 2 diabetes, renowned for its ability to lower high blood sugar effectively.

Unlike some other diabetes medications, metformin does not increase insulin production. Instead, it focuses on improving how the body uses existing insulin, making it an essential option for individuals with insulin resistance.

The primary mechanism of metformin is its ability to reduce glucose production in the liver, a process known as gluconeogenesis. This helps to lower fasting blood sugar levels, which is particularly beneficial for individuals with type 2 diabetes, whose livers often produce excessive amounts of glucose.

Let’s look at how metformin affects the body. 

• Reducing Hepatic Glucose Production: One of the primary mechanisms of metformin is its ability to reduce the amount of glucose produced by the liver. In individuals with type 2 diabetes, the liver often produces excess glucose, contributing to high blood sugar levels. Metformin inhibits this process by acting on the enzyme AMP-activated protein kinase (AMPK), which regulates energy balance in cells.
• Increasing Insulin Sensitivity: Metformin also enhances the body’s sensitivity to insulin, a hormone essential for regulating blood sugar levels. By improving insulin sensitivity, the medication helps the body use glucose more effectively, reducing insulin resistance, a hallmark of type 2 diabetes.
• Delaying Intestinal Glucose Absorption: Another beneficial action of metformin is its ability to slow the absorption of glucose in the intestines. This helps moderate blood sugar spikes after meals, contributing to overall glycemic control.
• Weight-Neutral and Cardiovascular Benefits: Unlike other diabetes medications, metformin is considered weight-neutral or even weight-reducing. This makes it a popular choice for patients struggling with obesity. Additionally, metformin is associated with improved cardiovascular outcomes, including reduced risk of heart attack and stroke in diabetic patients.

Side Effects of Metformin

Metformin helps to control blood sugar levels by improving insulin sensitivity and reducing glucose production in the liver.

However, while effective, it does come with a range of side effects that can affect some users. The most commonly reported side effects are gastrointestinal (GI), including nausea, diarrhea, and bloating. These typically occur early in treatment and often subside as the body adjusts.

However, some metformin side effects can be more persistent and may require medical intervention. Less common but more serious issues, such as vitamin B12 deficiency and lactic acidosis, also warrant attention.

It’s important for patients to be aware of the potential side effects of metformin, as well as how to manage or prevent them. Below, we delve into each side effect, discussing the causes, symptoms, and ways to manage them.

Regenics is committed to helping patients navigate their health journeys effectively. Our advanced services, including vitamin B12 injection kits, allow patients to nutrient deficiencies often associated with long-term metformin use.

Nausea and Vomiting

Nausea is one of the most common side effects experienced by metformin users.

It typically occurs when the medication is taken on an empty stomach or when the dosage is too high for the body to handle. Although not everyone will experience this, those who do often report that it can be debilitating, especially in the early stages of treatment. Vomiting may follow if the nausea is severe enough.

Causes

Metformin alters the function of the stomach and intestines, leading to changes in how food is processed. This can result in irritation of the stomach lining, contributing to stomach pain and nausea. Additionally, metformin slows down gastric emptying, which can make the stomach feel fuller and cause discomfort.

Symptoms

• Feeling nauseous or lightheaded.
• An aversion to food.
• Episodes of vomiting, particularly in the mornings or after taking the medication.
• Loss of appetite or changes in taste perception which can make it harder to eat properly.

Management and Prevention

• Take metformin with a meal or snack to reduce stomach pain and irritation.
• Start with a low dose of metformin and gradually increase the dosage under your doctor’s supervision. This allows your body to adjust without overwhelming the stomach.
• Consider switching to an extended-release version of metformin. This formulation is often better tolerated by the stomach and can help mitigate nausea.
• Avoid taking metformin on an empty stomach, as this can increase the likelihood of nausea and vomiting.
• If the symptoms persist or worsen, consult your healthcare provider for possible alternatives or adjustments to your treatment plan.

Diarrhea

Diarrhea is another commonly reported side effect of metformin, affecting a significant portion of patients, particularly in the early stages of treatment. It can range from mild to severe and can be quite distressing. While it often improves over time as the body adjusts, it can still cause significant discomfort in some individuals.

Causes

Metformin affects the intestines by altering gut motility and impacting the balance of gut microbiota.

It speeds up intestinal transit, leading to loose stools or diarrhea. This can be exacerbated by the dosage of metformin and may occur more frequently when higher doses are used. Additionally, metformin can disrupt the gut’s natural bacterial balance, further contributing to diarrhea.

Symptoms

• Frequent, watery stools.
• Abdominal cramping or bloating.
• Urgency to have a bowel movement.
• Dehydration due to excessive loss of fluids from severe diarrhoea.

Management and Prevention

• Take metformin with food to reduce the risk of gastrointestinal distress.
• Stay hydrated by drinking plenty of fluids, especially water or oral rehydration solutions, to replenish lost fluids.
• Consider reducing your intake of high-fiber or greasy foods, which can exacerbate diarrhea.
• Start with a low dose and gradually increase it to give your digestive system time to adjust.
• If diarrhea persists beyond a few weeks or is severe, talk to your doctor about alternative medications or adjusting your current dose.
• In some cases, switching to the extended-release formulation may alleviate gastrointestinal symptoms.

Bloating and Abdominal Discomfort

Bloating and abdominal discomfort are common gastrointestinal side effects of metformin, often experienced alongside diarrhea or nausea.

This discomfort may be experienced as a feeling of fullness, tightness, or gas accumulation in the abdomen. These symptoms can be particularly noticeable when metformin is first introduced into the treatment plan.

Causes

Metformin’s effect on the gastrointestinal system is largely due to its impact on gut motility and bacterial populations. It can slow down the movement of food through the digestive tract, causing bloating. Additionally, metformin can alter the microbial composition of the intestines, leading to increased gas production and discomfort.

Symptoms

• A feeling of fullness or heaviness in the stomach.
• Abdominal bloating or distention.
• Gas and frequent burping or passing gas.
• Mild to moderate cramping or discomfort.

Management and Prevention

• Eat smaller, more frequent meals instead of large meals, which can exacerbate bloating.
• Avoid carbonated drinks or gas-producing foods, such as beans, broccoli, and cabbage.
• Consider taking over-the-counter remedies, such as simethicone, which can help relieve gas.
• If bloating persists or becomes painful, talk to your doctor, who may suggest adjustments to your dose or switching to the extended-release form of metformin.
• Gentle physical activity, such as walking, can help relieve some of the discomfort associated with bloating.

Vitamin B12 Deficiency

Vitamin B12 deficiency is a less common but important side effect of long-term metformin use.

It may go unnoticed initially, but over time, it can lead to serious health issues if not addressed. Metformin interferes with vitamin B12 absorption in the intestines, particularly in individuals who have been using the drug for an extended period.

Causes

Metformin affects the gut lining and can alter the normal absorption process of B12, particularly in the small intestine. This happens because the drug modifies the microbial environment of the gut, which plays a role in nutrient absorption. The risk of B12 deficiency is higher in patients who take metformin for several years or those with gastrointestinal issues that further impair nutrient absorption.

Symptoms

• Fatigue, muscle weakness, or muscle pain.
• Numbness or tingling in the hands or feet.
• Difficulty walking or balance problems.
• Memory problems or confusion, which may mimic symptoms of dementia.
• Pale skin and shortness of breath.

Management and Prevention

• Regular blood tests should be performed to monitor vitamin B12 levels in patients using metformin long-term.
• If a deficiency is detected, vitamin B12 supplementation (either oral or via injection) is typically recommended.
• A B12-rich diet can help mitigate the effects of deficiency, including foods like meat, fish, eggs, dairy products, and fortified cereals.
• Patients with long-term metformin use should talk to their doctor about supplementing with B12 to prevent deficiency and its associated complications.

Regenics offer advanced diagnostic testing to monitor nutrient deficiencies, such as vitamin B12, ensuring that patients can proactively address any gaps in their treatment plans.

Lactic Acidosis

Lactic acidosis is a rare but very serious side effect associated with metformin use. It occurs when lactic acid builds up in the bloodstream to dangerous levels, leading to an imbalance in the body’s pH. Although extremely rare, lactic acidosis can be fatal if not treated immediately.

Causes

Lactic acidosis happens when metformin accumulates in the body due to impaired kidney function, which hinders the elimination of the drug. Other risk factors include severe dehydration, liver disease, or alcohol use. When metformin builds up in the body, it can lead to lactic acid accumulation, causing the blood to become more acidic.

Symptoms

• Severe muscle pain or muscle weakness.
• Fast or shallow breathing.
• Unusual fatigue or drowsiness.
• Nausea, vomiting, and abdominal pain.
• Confusion or dizziness.

Management and Prevention

• Ensure that kidney function is regularly monitored through blood tests.
• Stop taking metformin immediately if you experience any symptoms of lactic acidosis, and seek emergency medical attention.
• Patients should avoid dehydration by drinking plenty of fluids, especially when ill or exposed to heat.
• Alcohol consumption should be limited or avoided, as it can increase the risk of lactic acidosis.

Conclusion

Metformin remains a vital tool in the management of type 2 diabetes, offering numerous benefits, including low blood sugar control, weight neutrality, and cardiovascular protection.

However, like any medication, it comes with potential side effects that patients should be aware of. While most side effects are mild and manageable, others, such as vitamin B12 deficiency or lactic acidosis, require careful monitoring and proactive management. Regular communication with your healthcare provider and routine check-ups are essential for minimizing risks and optimizing treatment outcomes.

Understanding how metformin works and its potential side effects empowers patients to take charge of their health. By staying informed, you can make the most of this valuable medication while minimizing its impact on your quality of life.