Signs that metformin (Glucophage) is working and how to know it's not working

Key takeaways

• Metformin, while primarily used for diabetes and PCOS management, can also assist in weight management.
• Signs that metformin is effective include reduced blood sugar levels, weight loss, regular periods, and improved symptoms. Conversely, signs that metformin is not working include high blood glucose levels, worsening symptoms or no improvement in symptoms. 
• It is important to consult your healthcare provider if you notice that metformin is not adequately managing your condition.

Metformin (Glucophage) is an antidiabetic medication, which belongs to the Biguanide class, used mainly for managing type 2 diabetes. According to the American Diabetes Association (ADA), it has been chosen as the first-line drug for the treatment of type 2 diabetes in adults and also in children above the age of 10. Metformin is also used in the management of polycystic ovary syndrome (PCOS).

Metformin reduces blood sugar (glucose) levels by improving the responsiveness of surrounding tissues to insulin (a hormone that enables body cells to utilize glucose for energy), leading to a decrease in circulating insulin levels.

Additionally, this drug suppresses glucose production by the liver while simultaneously promoting glucose uptake by peripheral tissues, thereby leaving less glucose in the blood. 

The importance of metformin in PCOS lies in its ability to lower insulin levels, which results in reduced levels of luteinizing hormone and androgen. Normalizing these hormones aids in the regulation of the menstrual cycle in women.

Even though metformin is not a medication that was primarily designed to be used for weight loss, neither has it been approved for weight loss officially, studies have indicated it is effective in weight reduction. Some studies have shown that it is a favorable weight-loss option for people who are overweight and have an increased risk of developing diabetes.

What are the signs that metformin is working?

Below are signs and symptoms that indicate metformin is working. 

For polycystic ovarian syndrome (PCOS)

Signs that metformin is working for PCOS include:

• Reduced body mass index (BMI): A sign that metformin is effective for PCOS is a reduction in body mass index. Research has shown that metformin may help reduce BMI in overweight people who have PCOS.
• Regular menstrual cycle: One of the features of PCOS is irregular periods. Hence, another sign that metformin is working is the restoration of regular menstrual cycles.
• Reduction in some symptoms of PCOS: Metformin can reduce other symptoms of PCOS, such as hirsutism (excessive hair growth on the face, back, chest), hair loss, acne, and oily skin which are usually a result of high levels of androgens.

Some other signs that metformin is working for PCOS include a reduced risk of heart disease, low cholesterol levels, low insulin and blood sugar levels, and improved fertility.

For diabetes

Signs that metformin is working for diabetes include:

• Reduced blood sugar levels: The first and primary sign that metformin is effective in the management of diabetes is a decrease in blood glucose levels. Regularly monitoring blood sugar levels will show a gradual decrease in sugar levels as a result of metformin intake.
• Decrease in HbA1c levels: Hemoglobin A1C (HbA1C) is a marker of long-term sugar control; it measures your average blood glucose level over the past two to three months. A reduction in HbA1c levels is definitely a sign that metformin is working for your diabetes.
• Weight loss: Metformin has been proven to cause weight loss in people taking it. Therefore, if a person taking metformin begins to lose some weight, it indicates that the medication is working.
• Reduced risk of diabetic complications: There is a reduced risk of chronic complications such as cardiovascular diseases and nerve damage in patients with diabetes who are on metformin, which is also a sure sign that metformin is working.

How long it takes metformin to start working

Metformin usually begins to exert its effects within approximately 3 hours after administration, although the exact timing may vary among individuals. 

Metformin's effects persist due to its relatively long half-life of about 20 hours; this allows for sustained regulation of blood sugar levels. The half-life represents the time it takes for half of the drug to be eliminated from the body.

Signs that metformin is not working

For some people, despite adherence to treatment and lifestyle modifications, metformin may not be the ideal treatment for them and, in such cases, may not effectively manage their condition.

There are several signs that metformin may not be effectively managing a patient's condition, including:

• Elevated blood glucose levels: If metformin is not working for you, your blood sugar levels will be persistently high. This can be worrisome. It is important to consult your doctor to learn the next steps to take.
• Increased HbA1c levels: Because metformin is not working, HbA1c levels would increase.
• No improvement in symptoms: Symptoms do not improve if metformin is not working. In individuals with PCOS, the irregular menstrual cycle, weight gain, hirsutism, hair loss, and acne, among other symptoms, do not get better.
• Worsening or progression of diabetes complications: There is a greater risk of chronic diabetic complications as a result of metformin not being effective. These complications can include cardiovascular diseases, neuropathy, nephropathy, retinopathy, and other complications associated with diabetes.

What to do if metformin is not working for you

Many people take matters concerning their health into their own hands, and this often leads to adverse consequences. If you find out that your metformin is no longer working for you, you might want to increase the dosage yourself, but you should not do that. 

The first thing you should do upon finding out that metformin is not working is to consult your healthcare professional, either a doctor or a pharmacist. The professional may adjust your dose, conduct laboratory tests to determine if there are any problems, or suggest alternative treatments. Also, ensure that you modify your lifestyle to maximize treatment outcomes.

Tips for maximizing the benefits of metformin

To maximize the benefits of metformin and improve its effectiveness, consider the tips below:

• Taking metformin with food to reduce gastrointestinal side effects
• Exercising regularly; e.g., walking, cycling, jogging
• Eating healthy foods rich in vitamins, such as fruits and vegetables, proteins, and whole grains
• Avoiding processed sugars
• Quitting or reducing smoking (if you smoke)
• Taking your medication as instructed by your doctor
• Reducing alcohol intake
• Avoiding stress
• Getting enough rest

Other alternatives to metformin

As a result of some side effects of metformin and also the fact that it may not be ideal for patients with kidney and liver problems, doctors may sometimes need to prescribe alternative medications to their patients.

Other alternatives to metformin for the treatment of diabetes, PCOS, and weight loss include:

1. SGLT-2 inhibitors

Sodium-glucose co-transporter 2 inhibitors are medications used to treat high levels of blood glucose in type 2 diabetes. They block glucose and sodium reabsorption in the kidneys. 

SGLT-2 inhibitors such as empagliflozin, canagliflozin, and dapagliflozin have been proven to be alternatives to metformin in effectively managing diabetes, PCOS, and its associated obesity.

2. GLP-1 Ras

Glucagon-like peptide-1 receptor agonists are antidiabetic agents that make the muscles and liver more sensitive to insulin sensitivity by directly blocking the infiltration of macrophages, thereby inhibiting inflammation. These are also alternatives to metformin. An example is liraglutide.

3. DPP-4 inhibitors

Dipeptidyl peptidase-4 inhibitors, commonly referred to as gliptins, are the second or third drug of choice after metformin. They block DPP-4, the enzyme that breaks down GLP-1 (Glucagon-like peptide-1). 

Sitagliptin, an example of DPP-4 inhibitors, has been proven to be an alternative for PCOS patients who are intolerant to metformin.

4. Acarbose

Acarbose slows down the breakdown of food into glucose in the body, helping to prevent blood sugar levels from spiking after meals. It is usually used alone or with other medications and a proper diet to manage type 2 diabetes.

It has been found that acarbose leads to a reduction of about 3 kg/m2 in BMI in PCOS patients, hence a good alternative to metformin.

When to speak to a doctor

If you experience inadequate results or adverse effects from metformin, it is essential to consult your healthcare provider promptly. Your doctor can assess your situation, evaluate treatment effectiveness, and recommend appropriate adjustments or alternative treatment strategies based on your specific needs and medical history.