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Signs metformin is not working

Learn the symptoms that indicate metformin may not work and what to do next to manage Type 2 diabetes or PCOS
By | Updated on Jul. 10, 2025 Medically reviewed by Karen Berger, Pharm.D.
Rx pill bottle: Signs metformin is not working

Key takeaways

  • Metformin is commonly prescribed for Type 2 diabetes, prediabetes, PCOS, and off-label for weight loss. Metformin works by increasing insulin sensitivity and lowering glucose production in the liver.

  • Unexplained increases in blood sugar levels may indicate metformin’s ineffectiveness, necessitating consultation with a healthcare provider for possible dosage adjustments or alternative treatments.

  • If metformin is ineffective, alternatives include SGLT2 inhibitors, GLP-1 agonists, thiazolidinediones, DPP-4 inhibitors, or sulfonylureas, often combined with lifestyle changes like diet and exercise.

In this article:

Metformin is a generic diabetes medication frequently prescribed as a first-line drug (along with diet and exercise) to help control blood sugar in patients with Type 2 diabetes. You may also recognize metformin by its brand name, Glucophage. Although the brand-name drug is no longer available in the United States, generic versions are commonly used. 

Type 2 diabetes occurs when the body is unable to produce or use insulin properly, which results in high glucose (sugar) levels. Metformin, which comes in immediate and extended-release forms, is generally effective as a diabetes medication in controlling blood glucose levels, especially when combined with lifestyle changes. However, not everyone’s body responds the same to drug treatments. 

Unexplained increases in blood sugar may be the first indication that metformin is not working. Knowing what additional symptoms may point to metformin’s potential ineffectiveness is crucial for seeking alternate therapies.

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Signs metformin is not working

The full effects of blood glucose control may not be seen for up to two to three months, but improvements in blood glucose control may be detectable in one to two weeks. However, over time, the effectiveness of metformin may decrease and no longer work for its prescribed use. The following signs can be indications that metformin is no longer working. 

Type 2 diabetes and prediabetes 

A rise in blood sugar levels (hyperglycemia) is typically the first sign that metformin is no longer working for those with Type 2 diabetes or its precursor, prediabetes. Symptoms of hyperglycemia include:

  • High blood sugar
  • Increased thirst and/or hunger
  • Blurred vision
  • Frequent urination
  • Headache
  • Fatigue (feeling weak, tired)
  • Weight loss
  • Vaginal and skin infections
  • Slow-healing cuts and sores

If any of these signs are present, a hemoglobin A1C (HbA1c) blood test requested by a healthcare professional can determine if there has been a rise in previous blood sugar levels over the last few months. If metformin is not working to lower a person’s blood glucose, a dosage adjustment, an alternative or additional medication, or an insulin regimen may be recommended. 

PCOS

When prescribed for PCOS, metformin treatment may take several months to improve menstrual function and increase fertility. If a decrease in excessive hair growth, acne, and weight gain, as well as improved ovulation and menstrual regulation, is not noticed in this time frame, it may be beneficial to contact your healthcare provider to discuss whether or not a metformin prescription is providing the benefits to aid in managing PCOS. 

Weight loss

Metformin is sometimes prescribed off-label (for a non-FDA-approved use) for weight loss. If you are adhering to your medication regimen, following the lifestyle changes recommended by your healthcare provider, and do not see a slight weight loss after a few months, contact your healthcare provider. They may make some changes to your regimen, or, if you have elevated blood sugar, they may recommend that you keep taking metformin even if you do not lose weight, for its benefits on blood sugar control. 

What to do if metformin is not working

If a person suspects that metformin is not working, contacting a healthcare provider for medical advice should be the first step. It is important to understand that metformin may take some time to work, and desired results may not be noticeable right away. Some adverse effects, such as chest pain or rash, may be severe. Call a healthcare provider right away or seek emergency care if any of these signs are encountered. A new medication regimen may be initiated if a doctor determines that metformin is not working. Many prescription medications can replace or work alongside metformin—many people need to take more than one medicine for blood sugar control.

Alternatives to metformin

Metformin is in a drug class called biguanides. Biguanides help reduce the amount of sugar the liver makes while improving insulin sensitivity, which helps reduce high blood sugar. Synjardy, Invokamet, and Trijardy XR are common combination drugs that contain metformin as an ingredient (along with other drugs from different classes) and are also used for treating Type 2 diabetes. Medication for Type 2 diabetes is usually accompanied by dietary and lifestyle/exercise changes, which you can discuss with your healthcare provider. Other drug classes have proven beneficial, including:

1. SGLT2 inhibitors

SGLT2 inhibitors help block glucose (sugar) from being reabsorbed by helping the kidneys to eliminate sugar in the urine, which aids in the lowering of glucose levels. Drugs in the SGLT2 inhibitor class include:

2. GLP-1 receptor agonists 

GLP-1 receptor agonists are commonly used for Type 2 diabetes, weight loss, and cardiovascular risk reduction—the FDA-approved uses depend on the specific drug. Common side effects are mostly gastrointestinal, including nausea, vomiting, diarrhea, constipation, and stomach pain. GLP-1 drugs, as well as similar drugs known as dual GIP/GLP-1 receptor agonists, are available in both injectable and oral formulations and include drugs such as:

  • Ozempic, Wegovy (semaglutide injectable)
  • Rybelsus (semaglutide oral)
  • Mounjaro, Zepbound (tirzepatide injectable)

3. Thiazolidinediones

Also known as glitazones, thiazolidinediones are oral insulin-sensitizing drugs used to treat Type 2 diabetes mellitus. They lower blood sugar with little chance of hypoglycemia (low blood sugar) and may have advantages against atherosclerosis. Thiazolidinediones may also be used to treat polycystic ovarian syndrome due to their potential to enhance ovulation, lower insulin resistance, and enhance endothelial function. Commonly prescribed thiazolidinediones include:

RELATED: Thiazolidinediones: Uses, common brands, and safety info

4. Dipeptidyl peptidase-4 (DPP-4) inhibitors

Used with diet and exercise, DPP-4 inhibitors reduce blood sugar by assisting the body in raising its post-meal insulin levels. Also known as gliptins, DPP-4 inhibitors are typically prescribed to patients with Type 2 diabetes who do not respond favorably to conventional diabetes medications such as metformin. DPP-4 inhibitors include:

5. Sulfonylureas

Sulfonylureas are a class of drug used for Type 2 diabetes. These are some of the older drugs developed for diabetes. They work by stimulating the pancreas to make insulin. Side effects include hypoglycemia, weight gain, dizziness, headache, nausea, and diarrhea. Examples of sulfonylureas include:

What’s next when metformin isn’t enough for Type 2 diabetes?

Metformin is used as first-line therapy because it is both extremely effective and reasonably priced. If you are not seeing desired results, talk to your healthcare provider. Sometimes, an additional drug may be needed, which can be effective when used in combination with metformin. This can be done with single-ingredient drugs or combination drugs. 

If cost is a concern, using a SingleCare discount card can help with additional savings at local pharmacies. Stop taking metformin only after consulting a healthcare professional for medical advice. Hyperglycemia may result if metformin is abruptly stopped. Metformin should only be stopped abruptly in the case of a severe allergic reaction or other emergency situation.

RELATED: How much is metformin without insurance?

When to switch from metformin to insulin?

Many Type 2 diabetes patients require treatment with insulin, either as a stand-alone medication or as an addition to an oral regimen, because they are unable to achieve adequate glycemic control with oral medications (or injectable non-insulin medications like Ozempic). The start of insulin may be recommended if there is evidence of long-term and chronic hyperglycemia, given how quickly and effectively insulin lowers blood sugar levels. A medical team may recommend using insulin if glucose targets are unable to be made after being diagnosed (whether this is due to a condition that has worsened over time, the ineffectiveness of present treatments to lower your glucose, or the development of problems occurring).

What are the steps you should take if metformin stops working?

Your diabetes care team must reevaluate your plan (including lifestyle changes and medications) if metformin no longer keeps blood sugar levels within the desired range. Talking to a healthcare provider about concerns should always be the first step in seeking alternative treatments.

How to take metformin to maximize benefits

Lifestyle changes, such as exercise and a healthy diet, are effective for improving diabetes management and cardiovascular health while taking metformin. Both of these lifestyle modifications can help to maximize the benefits of metformin.

RELATED: How to lower blood sugar naturally

The DASH (Dietary Approaches to Stop Hypertension) plan is a wholesome, well-balanced, and long-lasting eating regimen that can help with a variety of health issues, such as hypertension (high blood pressure), high cholesterol, insulin resistance, and obesity. Some of the most beneficial foods to eat (along with taking metformin) to help blood sugar control include non-starchy vegetables such as asparagus, broccoli, cauliflower, leafy greens, salad greens, squash, and green beans, to name a few. Avoiding saturated fats and consuming lean meats and plant-based proteins are also beneficial. It is suggested that sugary drinks and foods high in carbohydrates (such as cookies and chips) be avoided to help prevent excessive blood sugar spikes after meals. 

Metformin may contribute to a vitamin B12 deficiency. A healthcare provider may recommend B12 testing be done while taking metformin.

Exercise encourages muscle cells to take in and use more sugar, lowering blood sugar levels. It can also lower the chance of developing diabetes and make it simpler to manage a current diagnosis. Make it a point to get some exercise for at least 30 minutes a day, five days a week (or as directed by your doctor). A simple 10-minute walk three times a day is an effective way to accomplish this goal.

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