Metformin is an effective treatment option for type 2 diabetes. However, over time the effects of metformin may decrease or stop working. This article discusses the signs to recognize when metformin is not working.
Metformin is a first-line agent in the treatment of newly diagnosed type 2 diabetes.
Metformin is an "insulin sensitizer" that improves the body's response to insulin.
Over time, metformin may begin to wear off which is seen by gradually increasing blood sugar levels and symptoms of high blood sugar.
When metformin stops working it can require lifestyle changes, such as increasing exercise, making dietary improvements, or the addition or change of anti-diabetic agents.
Metformin and diabetes
Metformin has been available for the treatment of type 2 diabetes for nearly 30 years. Currently, it is considered a first-line treatment option in patients with newly diagnosed type 2 diabetes. Although it can be used in certain people with type 1 diabetes (those with insulin resistance) it is more commonly used in type 2.
Metformin works by two main mechanisms:
- Reduces the production of glucose (sugar) by the liver, helping to lower blood sugar levels.
- Increases the body's response to insulin making it more effective in lowering blood sugar levels.
Due to the ability of metformin to improve the body's response to insulin, it is commonly referred to as an "insulin sensitizer". It can be used in combination with many of the other diabetic agents available or by itself. However, for metformin to be effective, the body must be able to produce insulin on its own.
Metformin and aging
Metformin has been linked to anti-aging properties in many studies. However, many of these studies showing longevity improvements have been conducted in flies, mice, and worms.
In humans, metformin has been shown to reduce the risk of developing dementia, cognitive decline, and certain types of cancer. It has been shown to have increased survival rates when used in people with diabetes that also have cardiovascular disease and certain types of cancer. However, these effects need to be further studied to understand more about how metformin increases one's life span.
These effects are a product of prolonged use of metformin and currently, there is no way to assure metformin's anti-aging properties are working. Therefore, to determine if metformin is working, healthcare clinicians use blood sugar levels to monitor. Although, the fact that metformin is not helping with your diabetes does not necessarily mean it is not helping with its anti-aging properties. This area still requires significantly more research to answer all these questions.
How metformin helps patients with diabetes
The effects of metformin for patients with type 2 diabetes include the following:
- Reducing fasting glucose. Metformin can help reduce fasting blood glucose levels, as well as blood glucose after meals (post-prandial levels). In addition, unlike insulin and glipizide, metformin is less likely to cause weight gain making it particularly helpful in obese people with type 2 diabetes.
- Reducing cardiovascular disease risk. In addition to lowering blood sugar levels, metformin reduces the risk of cardiovascular disease in diabetes. A lower risk of cardiovascular-related deaths has been seen in patients with diabetes using metformin.
- Lower rates of cognitive disease and stroke. Fewer strokes and a lower rate of dementia have been observed in patients taking metformin.
The positive effects on blood sugar levels and the additional health benefits make metformin a popular choice for people with type 2 diabetes. However, over time metformin may not be as effective at lowering blood sugar levels and may stop working altogether.
Signs metformin is not working
As stated above, metformin requires the pancreas to be able to produce insulin for it to work. Despite metformin's best effort, the pancreas can become overworked and lose its ability to produce sufficient insulin. Thus, causing metformin to be ineffective.
Although this may not be the only reason metformin is not working. Weight gain, unhealthy eating habits, reduced exercise, and not taking your medication can result in metformin being less effective. Therefore, it is important to identify these lifestyle changes as a possible explanation.
Regardless, when metformin is not working you begin to see elevations in your blood sugar levels. You may see increases in your daily readings or a gradual increase in your hemoglobin A1c despite no other changes in your life. As your blood sugar levels continue to increase you may notice symptoms of hyperglycemia (elevated blood glucose).
Signs of elevated blood sugar levels include:
- Increased thirst
- Frequent urination
- Increased appetite
- Blurred vision
Signs metformin is working
Unfortunately, you will not experience any specific signs that metformin is working. Therefore, the best way is to monitor blood sugar levels at home. If you notice your sugar levels are getting closer to the goals set by your doctor it is likely that metformin is working.
However, random elevations in your blood sugar do not mean metformin has stopped working. Rather, if you see a gradual increase over weeks to months, without any improvements, metformin may not be working. If your sugars remain controlled, then it's working and doing its job.
Is metformin not working a concern?
Yes. Prolonged elevations in blood sugar levels can have negative effects on the body. These elevated levels are associated with complications of diabetes such as kidney failure, blindness, heart disease, and neuropathy. Therefore, identifying these elevations early is very important.
If you start to notice a trend of increased blood sugar readings on daily fingersticks or any signs of hyperglycemia, contact your doctor as soon as possible. They can help you identify possible causes for the worsening blood glucose control and determine a solution.
In some cases, altering your diet or increasing your daily exercise can be enough to regain control of your blood sugar levels. However, changing medications or adding a new medication may be indicated.
Options beyond metformin
Since metformin was approved by the FDA, many new medications have been developed. The new developments give doctors many other options. Here is a quick review of some alternatives for the treatment of diabetes.
- Sulfonylureas. These work by stimulating the pancreas to secrete more insulin thus improving blood sugar control. They have an increased risk of causing low blood sugar (hypoglycemia) and can be added to metformin. This includes drugs such as glipizide, glyburide, and glimepiride.
- Thiazolidinediones (TZDs). Pioglitazone and rosiglitazone are two examples of TZDs used for diabetes. They improve the body's response to insulin and reduce glucose production by the liver. TZDs can increase fluid retention and may worsen heart failure.
- Glucagon-like peptide 1 (GLP-1) analog. Sensitizes the body to produce insulin in response to glucose, as well as reducing the body's production of glucose. This class of medications is effective in causing more weight loss than other diabetic agents, but all of them except semaglutide must be injected. Other members include liraglutide, dulaglutide, exenatide, and lixisenatide.
- Dipeptidyl peptidase (DPP-4) inhibitors. These inhibit the enzyme that breaks down natural GLP-1 and glucose-dependent insulinotropic polypeptides producing similar effects to the GLP-1 analogs. A negative associated with this class is their potential to cause heart failure. This class includes sitagliptin, saxagliptin, linagliptin, and alogliptin.
- Sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Inhibiting SGLT-2 in the kidney causes the body to excrete more glucose into the urine rather than reabsorbing it. They are associated with improved outcomes in heart and kidney disease patients but can cause urinary and genital infections. Bexagliflozin, canagliflozin, dapagliflozin, and empagliflozin are available SGLT-2 inhibitors.
How can I make metformin more effective?
Taking metformin with meals or a snack can reduce GI upset. Eating a low-carb diet can help improve blood sugar levels. Regularly exercising and maintaining a healthy weight can provide significant benefits and help metformin and other diabetes medications to be more effective.
My metformin stopped working, should I take more?
Do not increase or decrease your medication without first talking to your doctor. The max dose of metformin is 2,000 mg a day. So, if you are taking less than 2,000 mg, your doctor may want to raise the dose. However, they may want to start a new medication.
Can metformin become ineffective?
Over time metformin may become less effective. The first sign of it not working is an increase in blood sugar levels. This can be due to changes in your lifestyle or simply because the medication is no longer able to manage your diabetes. If this occurs, talk to your doctor.
- StatPearls. Metformin.
- Diabetology and Metabolic Syndrome. Metformin: an old but still the best treatment for type 2 diabetes.
- American Diabetes Association. What are my options for type 2 diabetes medications?
- Cold Spring Harbor Perspectives in Medicine. Metformin: a hopeful promise in aging research.