Metformin is the most commonly prescribed drug used for the treatment of type 2 diabetes. Even so, not everyone responds to metformin in the same way, and, over time, the drug can start to lose its effectiveness and stop working entirely.
When used on its own, metformin is often extremely effective in controlling blood glucose (sugar). But, for most people, this effect will gradually wane, requiring the metformin dose to be increased or another diabetes drug to be added to the treatment plan.
This article explains how metformin works and signs that the drug may no longer be working. It also outlines some of the available options should metformin fail to control your blood sugar.
How Metformin Works
Metformin (sold under the brand names Fortamet, Glucophage, Glumetza, and others) is an oral drug used together with healthy eating, exercise, and weight loss to manage your blood sugar.
Its main function is to stop the liver from releasing too much glucose into the blood. The drug also helps increase your body’s response to insulin (the hormone made by the pancreas that helps your body utilize glucose for energy).
You can take metformin on its own or in combination with other diabetes medications, including insulin, to help treat type 2 diabetes. People with type 1 diabetes who have insulin resistance can also use it.
Signs That Metformin Is Not Working
When taken as prescribed, metformin is highly effective at lowering blood sugar. Even so, you may experience occasional increases in blood sugar due to stress, a large meal, and other factors.
Most of the time, you don’t need to worry about these occasional increases. It is only when you notice a pattern of high blood sugar (hyperglycemia) that you should speak with your healthcare provider.
The pattern may not be due to the waning effects of the drug. It could be that you are not following dietary guidelines, have stopped exercising, or have gained excessive weight. Or, it could be that you're not taking the drug as prescribed.
Whatever the reason, the very first indication that metformin is not working is when your blood glucose levels are high. You may only realize this when your hemoglobin A1C (a three-month average of blood sugar) is tested at your healthcare provider’s office. Or, you may start to notice when using a blood glucose monitor.
You may also start to experience signs and symptoms of hyperglycemia, including:
- Blurred vision
- Frequent urination
- Increased hunger
- Increased thirst
- Nausea or vomiting
Why Metformin Failure Is a Concern
Metformin is prescribed because your healthcare provider believes that you need it to help control your blood sugar. It is often prescribed after lifestyle interventions (like diet, exercise, and weight loss) fail to provide glucose control.
If metformin is unable to control your blood sugar, you need to take action. In people with uncontrolled or poorly controlled diabetes, excessive accumulation of glucose in the bloodstream can cause progressive damage to blood vessels, nerves, and organs.
Among the possible complications of uncontrolled diabetes are:
- Hypertension (high blood pressure)
- Coronary artery disease (narrowing of the arteries of the heart)
- Peripheral artery disease (narrowing of the arteries outside of the heart or brain)
- Stroke (damage to the brain caused by reduced blood flow)
- Chronic kidney disease (progressive decline in kidney function)
- Diabetic retinopathy (diabetes-related eye damage)
- Diabetic neuropathy (diabetes-related nerve pain)
- Glaucoma (eye problems caused by optic nerve damage)
- Cataracts (clouding of the eye lens)
What to Do If Metformin Isn’t Working
If metformin is not working as it should, there are different courses of action you may need to take depending on when the failure occurred.
If you just started taking metformin and don't see an improvement in your blood sugar after several weeks, contact your healthcare provider. You may not be taking the drug correctly, or your dose could be too low.
You should also let your healthcare provider know if you are not taking metformin as prescribed because of intolerable side effects like nausea and vomiting. They may be able to switch you to an extended-release version of metformin which may lessen your side effects.
If you have been taking metformin for several years and notice that your blood sugar is suddenly starting to rise, your healthcare provider may need to add another medication to your treatment plan. There is no standardized approach as to which drug should be added, but some of the more common options include:
- Actos (pioglitazone)
- DPP-4I inhibitors, including Januvia (sitagliptin), Tradjenta (linagliptin), Onglyza (saxagliptin), and Nesina (alogliptin)
- GLP-1 agonists, including Bydureon (exenatide), Byetta (exenatide, Saxenda (liraglutide), Mounjaro (tirzepatide), and Adlyxin (lixisenatide)
- Injectable insulin
- SGLT2 inhibitors, including Invokana (canagliflozin), Farxiga (dapagliflozin), Jardiance (empagliflozin), and Steglatro (ertugliflozin)
- Sulfonylureas, including Amaryl (glimepiride), Glynase (glyburide), and Glucotrol (glipizide)
Metformin is an oral diabetes medication that can help reduce blood sugar levels in people with type 2 diabetes. Although it is the most common drug used for the first-line treatment of type 2 diabetes, it doesn't work the same for all people and can begin to lose its effectiveness over time.
Unexplained increases in blood sugar may be the first sign that metformin has stopped working. You may also experience symptoms of hyperglycemia such as excessive thirst or hunger, fatigue, and blurry vision.
Whatever the cause of the treatment failure, action needs to be taken to restore glucose control and prevent diabetes complications. This may involve improving drug adherence, correcting dosing mistakes, increasing the metformin dose, or adding another diabetes drug to the treatment plan.
A Word From Verywell
Metformin is not a “cure” for type 2 diabetes, and medication alone is not enough to keep your blood sugar in control. If you eat poorly or live an otherwise inactive lifestyle, metformin may only go so far in controlling your blood sugar.
No matter how early or advanced your diabetes is, good lifestyle choices are needed to ensure your long-term health and well-begin. This involves eating a healthy diet, exercising regularly, taking your medications as prescribed, and losing weight if you are overweight or have obesity.
If needed, ask your healthcare provider for a referral to a nutritionist or personal trainer who can help.
— Update: 05-01-2023 — cohaitungchi.com found an additional article What Are the Signs Metformin Is Not Working? What to Look Out For from the website khealth.com for the keyword what next when metformin isn’t enough for type 2 diabetes.
Metformin is one of the most common diabetes medications.
However, not everyone with diabetes responds to the medication.
In other cases, it may work for a while and then become less effective at managing high blood sugar levels.
If metformin stops working, a medical provider may add another diabetes medication to provide more support, or they may prescribe a different medicine.
In this article, we’ll explore signs that metformin is not working as it should, as well as what to do if it is not.
We’ll also discuss common side effects and when to see a healthcare provider.
Signs Metformin Is Not Working
Although metformin is highly effective at controlling blood glucose, it may work less effectively over time.
If you notice any of the following symptoms while taking metformin, talk to a healthcare provider.
The medication may not be working for you.
- High blood sugar levels: This is usually the first sign that metformin is not working as it should. Blood glucose levels should be less than 100 mg/DL when fasting and less than 140 mg/DL after meals. However, the appropriate diet is important to controlling glucose as well.
- Elevated hemoglobin A1C: Blood work can check if your hemoglobin A1C is higher than it used to be or out of range. The hemoglobin A1c is an average glucose over 3 months time.
- Frequent urination: As glucose levels rise, the body eliminates more glucose via the kidneys. As this happens, you may need to pee more often.
- Increased hunger or thirst: Increased urination can disrupt levels of electrolytes and body fluids. This can result in symptoms such as excess hunger or thirst.
- Fatigue: Glucose is needed for energy in the body, but highly elevated blood sugar levels can increase fatigue. This is most likely as the body is not able to process the glucose effectively, if at all.
- Blurred vision: When blood glucose levels rise too high, it can lead to blurry vision.
Keep in mind, these signs do not necessarily indicate that metformin is not working.
They could also mean:
- Your diet has changed.
- You are being less physically active or are not getting enough exercise.
- You have gained weight.
- You are not taking the medication properly.
Why Metformin Failure Is a Concern
With type 2 diabetes, if blood glucose becomes harder to control or is not kept within range due to metformin failure, it can lead to serious health complications in the short and long term such as:
- Hypertension (high blood pressure)
- Coronary artery disease
- Peripheral artery disease
- Chronic kidney disease (CKD)
- Diabetic retinopathy (eye problems caused by diabetes)
- Diabetic neuropathy (nerve problems caused by diabetes)
- Diabetic nephropathy (kidney problems caused by diabetes)
How long does metformin take to work?
Metformin changes the way that the liver makes glucose, which takes time.
Metformin starts working 48 hours after you begin taking it; however, the full effects do not start to kick in until after 4-5 days.
Does metformin lose effectiveness over time?
You may need to increase metformin dosage over time to properly control glucose levels.
This can happen for a few reasons:
- Diet and lifestyle are not supporting glucose balance, requiring more medication to offset them. Keep in mind that metformin is designed to work with diet, exercise, and lifestyle changes, not to replace them.
- Diabetes is a chronic condition that may worsen over time based on other health factors, including age.
- Liver or kidney problems can change the way that the body uses medication, which can alter how effective metformin is.
There are other reasons why metformin may be less effective.
A medical provider can assess whether it’s best to add another medication or try a different drug.
What to Do If Metformin Isn’t Working
If metformin is not controlling blood glucose levels as expected, some changes may help:
- If you recently started taking metformin, you may need to wait longer for it to fully take effect. If you’ve been on metformin for at least three months talk to your medical provider. They may need to increase your dosage, or you may not be taking the medicine correctly.
- If you are not taking your medication regularly because of side effects, tell your medical provider. They can change your dosage, switch you to the extended-release form of metformin, or recommend a different medication.
- If you have been taking metformin for many years and notice your blood glucose or hemoglobin A1C levels rising, you may need another medication or an increase in dosage. Diabetes can progress, even when you are doing everything you can to manage it.
How to check if metformin is working
A medical provider can run a few tests to see how metformin is affecting your health:
- Blood work can check if your glucose, insulin, and HbA1C levels are in range. If they are, the medication is working.
- If your medical provider suspects that you are not tolerating metformin or you are experiencing side effects, they may test your vitamin B12 levels. Metformin can make it harder to absorb this nutrient, leading to a vitamin B12 deficiency. This can cause anemia.
Blood sugar goals
Your medical provider will tell you what your blood sugar target range should be.
For most people who have type 2 diabetes, the target for hemoglobin A1C is 7% or less.
Metformin Side Effects
Metformin may cause the following side effects. Many of these resolve as your body adjusts to the medication.
- Nausea and vomiting
- Bad taste in mouth
- Weight loss
In some cases, metformin can cause more serious side effects, like B12 deficiency or anemia.
Serious, potentially life-threatening lactic acidosis can occur if too much metformin builds up in the body.
If you notice sudden flushing, feelings of warmth, dizziness, nausea, or vomiting or generally feel unwell, tell your medical provider and seek emergency medical care.
Lactic acidosis can be fatal if not treated promptly.
When to See a Medical Provider
See your healthcare provider if you take metformin and notice that your blood glucose levels are not as controlled as they should be.
If you are concerned about taking metformin or worried that it is not working, they can perform lab tests and other assessments to determine the best course of care.
How K Health Can Help
Did you know you can access online urgent care with K Health?
Check your symptoms, explore conditions and treatments, and if needed, text with a healthcare provider in minutes.
K Health’s AI-powered app is HIPAA compliant and is based on 20 years of clinical data.
— Update: 06-01-2023 — cohaitungchi.com found an additional article When Type 2 Diabetes Treatment Fails, What’s Next? from the website www.everydayhealth.com for the keyword what next when metformin isn’t enough for type 2 diabetes.
For most people, type 2 diabetes changes over time — even for those who follow their treatment plan exactly as directed. Diabetes is a progressive disease, meaning your diet, exercise, and medication needs will likely change with time. That doesn’t mean you did something wrong; shifting gears is a natural part of managing a changing chronic disease like type 2 diabetes.
Your diabetes care team can help you adjust your treatment plan and manage your blood sugar levels. If a change is needed, your doctor may adjust your current medication, add new diabetes medications, or suggest starting an insulin regimen.
Why Your Diabetes Treatment Plan May Change
There are a number of factors that can contribute to a decline in blood sugar control, says Margaret Powers, PhD, RD, CDE, who has served as president of healthcare and education for the American Diabetes Association and is a registered dietitian, certified diabetes instructor, and research scientist at the Park Nicollet Health Clinic in Minneapolis.
When type 2 diabetes first develops, you may be insulin resistant, which means you make a lot of insulin, but your body can’t use it effectively, Dr. Powers says. Then, over time, you make less insulin and become insulin deficient. “This is seen a lot, but it doesn’t happen overnight; it’s a gradual process,” says Powers. Other factors can also affect blood sugar, including a significant change in weight, activity level, or diet or starting a new medication, she says.
Stress can also impact your treatment. When you’re chronically stressed, your body produces hormones that might cause your blood sugar to rise. An additional illness or a major change like a divorce, job loss, or loved one’s death can cause prolonged stress, which can raise blood sugar.
Stressful life changes may also affect how well people take their medication, adds Susan Weiner, RDN, a certified diabetes educator in New York and the American Association of Diabetes Educators’ 2015 Educator of the Year. “Before, there may have been someone who helped motivate and support the person with diabetes. And daily diabetes self-management can be challenging even under the best of circumstances,” she says.
If you need to change things up, it doesn’t necessarily mean you’ll need to adjust your medication regimen. It may just be a matter of refocusing on your food and activity plan, as well as reducing stress.
Consider taking these steps to get your type 2 diabetes treatment back on track.
Monitor your blood sugar and A1C levels to gauge treatment success
An A1C test measures your average blood glucose (sugar) levels over the past three months. It’s the test that’s used to diagnose prediabetes and diabetes and also to help track and manage the condition. Your results are reported with a percentage.
Generally speaking, a reading of less than 7 percent is usually optimal to prevent type 2 diabetes complications. Your target may be higher or lower, so be sure to talk to your diabetes care team about your personal A1C goal.
While A1C tests are a good indicator of how well treatment is working overall, Powers explains that the A1C reflects an average. That means you could actually be experiencing many highs and lows, depending on what you eat and whether you exercise, even if your A1C result seems normal.
That’s why at-home blood sugar testing as prescribed by your doctor is also important. Regular monitoring shows your blood sugar levels on a day-to-day basis. If your numbers aren’t consistently within your target range, you may need a change in treatment.
Most people with diabetes should see their doctors about every three to four months to get their A1C, blood pressure, blood sugar, and cholesterol levels checked and to reevaluate their treatment plan as necessary. You may need to see your doctor more or less frequently, depending on your treatment plan and blood sugar control. According to Powers, there are four critical times to have your diabetes self-management plan assessed:
- When you are newly diagnosed
- When complicating factors occur
- When you have transitions in care
There are many factors that can affect your A1C, so it’s important to review your diabetes management plan regularly so you don’t miss the opportunity to do what’s best for you.
Keep up with healthy lifestyle changes
Anyone who’s started a new diet or exercise program knows sticking to it for the long haul is often the most challenging part. But it’s essential to maintain lifestyle changes to get the best diabetes control, says Powers. Even diabetes medications, she says, won’t work on their own.
Important lifestyle changes to manage your diabetes include:
- Eating a healthy diet to keep your blood sugar levels stable, with the help of your diabetes educator or a registered dietitian. While there is no one-size-fits-all diet, for most people it means cutting back on calories and saturated fats; reducing carbohydrates and distributing them evenly throughout the day; and bumping up your intake of vegetables, fruits, and other high-fiber foods.
- Getting more physical activity, which helps lower blood sugar. Aim for 30 to 60 minutes most days of the week — everything from walking and gardening to swimming and biking — and combine that with two days of resistance training, such as weight lifting or yoga, for the best results.
- Losing weight, which also helps lower blood sugar levels. Even 5 to 10 pounds can make a difference.
Work with your doctor to adjust treatment as needed
While some people with diabetes can manage their blood sugar with lifestyle changes, including losing weight, eating a healthy diet, and exercising regularly, many others require diabetes medications. Metformin is a typical first medication for people with type 2 diabetes, says Powers. It works by decreasing the amount of sugar the liver produces and making muscle cells more sensitive to insulin so sugar can be absorbed.
If metformin no longer works for you, your doctor may add another drug to your treatment plan. “But there’s no magical second drug; the secondary options will depend on the individual,” she says.
Your doctor may prescribe other oral medications or noninsulin injectables. There are several different classes of diabetes medications that work to lower blood sugar in different ways. For instance, some trigger the pancreas to release more insulin, while others work in the intestines to block the breakdown of some carbohydrates or in the kidneys to increase the amount of sugar excreted in urine. Your doctor may suggest adding one or more of these to your medication plan. You’ll know your new medication is working if your A1C numbers shift down toward your goal.
If you’ve had type 2 diabetes for many years, there may come a time when the medications you’ve been taking and lifestyle changes you’ve made might not work anymore. As a result, insulin injections may be needed in people whose A1C numbers are very high, Powers says. Keep in mind that although insulin therapy used to be added only when other medications weren’t working, it’s sometimes started earlier these days for people with type 2 diabetes.
“Work with your healthcare provider, who will be able to recommend the best way to adjust your medications and insulin dosage so you can continue to properly manage your type 2 diabetes,” she says.
Stay positive when your type 2 diabetes changes
“Don’t feel like you’re in this alone,” Weiner says. Reach out to a friend, family member, healthcare provider, or certified diabetes educator for support.
Additionally, take measures to manage stress. “Recharge and do something you enjoy: Take a walk, cuddle a pet, listen to music, or treat yourself to a massage,” she says.
Additional reporting by Colleen de Bellefonds
— Update: 07-01-2023 — cohaitungchi.com found an additional article When Metformin Isn’t Enough: Effectiveness of Type 2 Drugs Compared from the website www.diabetesselfmanagement.com for the keyword what next when metformin isn’t enough for type 2 diabetes.
New study results, presented at the American Diabetes Association (ADA) 81st Scientific Sessions, show that liraglutide (Victoza) and basal insulin may be the best options for people with type 2 diabetes when metformin isn’t enough to achieve good glucose control.
The study, known as GRADE (Glycemia Reduction Approaches in Diabetes), was conducted between 2013 and 2021. At the time of their enrollment, participants were in their mid-50s, had received a type 2 diabetes diagnosis within the past five years, had an A1C level (a measure of long-term blood glucose control) between 6.8% and 8.5%, and were taking metformin, the first-line type 2 diabetes drug. Men accounted for about 65% of participants. About 66% of participants were non-Hispanic white, while 20% were Black, 19% were Hispanic or Latino, 4% were Asian, and 3% were American Indians or Alaska Natives.
As described in an article on the study at MedPage Today, participants in the study were randomly assigned to take one of four treatments in addition to metformin: glimepiride (Amaryl), sitagliptin (Januvia), liraglutide (Victoza), or insulin glargine (Lantus, Basaglar, Toujeo), a long-acting basal insulin. Each of these treatments comes from a completely different class of drugs, so the study wasn’t comparing similar drugs with one another. Glimepiride is a sulfonylurea, which works by making the pancreas produce more insulin. Sitagliptin is a DPP-4 inhibitor, which works by inhibiting the release of the hormone glucagon. Liraglutide is a GLP-1 receptor agonist, which works by increasing the release of insulin from the pancreas and reducing the release of glucagon.
To get cutting-edge diabetes news, strategies for blood glucose management, nutrition tips, healthy recipes, and more delivered straight to your inbox, sign up for our free newsletters!
Notably, the study didn’t include any SGLT2 inhibitors, a group of drugs that was still somewhat new at the time when GRADE was being designed. SGLT2 inhibitors have grown enormously in popularity since then, due to not just their glucose-lowering benefits, but also their positive impact on kidney health, a major area of concern for people with type 2 diabetes. This omission means that the results of the study may be of limited use, in the opinion of some diabetes experts, as noted in a Medscape article on the study.
Liraglutide, basal insulin tied to best glucose control
The main outcome that GRADE looked at was an A1C level of 7.0% or higher at some point, meaning that the most successful treatments had a lower number of participants who reached this endpoint. Insulin glargine came out on top at 67%, while liraglutide wasn’t far behind at 68%. Glimepiride had 72% of people reach this endpoint, and sitagliptin had 77%. These numbers indicate that both glimepiride and sitagliptin were significantly less effective than either insulin glargine or liraglutide for overall glucose control. During just the first year of treatment, people who took liraglutide had the best glucose control, with an average A1C level of 6.7%. But by the end of four years, some of the improvement seen with liraglutide had faded, and it ended up virtually tied with insulin glargine for overall A1C over the study period.
Liraglutide and insulin glargine saw participants maintain A1C within the target range for the longest average period of time — about 2.4 years for both. For glimepiride, this number was 2.2 years, and for sitagliptin it was 1.9 years.
The study’s second outcome of interest was an A1C level of 7.5% or higher at some point — again, an outcome where greater success meant avoiding this as much as possible. For this outcome, insulin glargine came out on top, with only 39% of participants having an A1C of 7.5% or higher. Liraglutide came in second at 46%, followed by glimepiride at 50%, and sitagliptin at 55%.
One additional benefit from taking liraglutide was an average weight loss of about 4 kilograms (8.8 pounds) during the first year of treatment. Participants who took sitagliptin also lost some weight over the four years of treatment, while those who took insulin glargine neither gained nor lost weight, on average. The lack of weight gain seen with basal insulin was considered an unexpectedly positive outcome, as was the fact that only about 1.5% of participants who took insulin experienced severe hypoglycemia (low blood glucose).
As always, talk to your doctor about the best treatment options if you already take metformin for type 2 diabetes, but your A1C level shows that you may need to take further steps to improve your blood glucose control.
Want to learn more about blood glucose management? See our “Blood Sugar Chart,” then read “Blood Sugar Monitoring: When to Check and Why” and “Strike the Spike II: How to Manage High Blood Glucose After Meals.”
Living with type 2 diabetes? Check out our free type 2 e-course!