Key takeaways:
Metformin is a first-choice medication for treating Type 2 diabetes. But if you can’t tolerate metformin or it’s not doing enough to help you reach your diabetes goals, you may need an alternative.
If you also have heart or kidney disease, glucagon-like peptide-1 (GLP-1) agonists like Ozempic (semaglutide) or sodium-glucose cotransporter-2 (SGLT2) inhibitors like Jardiance (empagliflozin) are good alternatives. If you have advanced kidney disease, insulin may be the best alternative.
If you take metformin in addition to another oral diabetes medication, there may be a pill that combines them both together. Talk to a healthcare professional about whether a combination pill is right for you.
Save on related medications
If you or a loved one are living with Type 2 diabetes, chances are you’ve heard of metformin. It’s a first-choice medication to lower blood glucose (blood sugar) among people living with diabetes, and it’s very commonly prescribed. It can also help some people lose weight, among other effects.
But is metformin the best medication to treat Type 2 diabetes? That depends. Despite metformin’s popularity, there may be an alternative that works better for you. This is especially the case if you can’t take or tolerate metformin.
Some people with diabetes might only need to take one medication for treatment. Others need to take more than one. Thankfully, there are different types of diabetes medications available. And many of them can be used in combination with each other.
Is metformin the best medication for Type 2 diabetes?
Experts traditionally recommend metformin as a first-choice medication for Type 2 diabetes. It can lower hemoglobin A1C (HbA1C or A1C) by up to 1.5% and doesn’t generally cause episodes of low blood sugar, also known as hypoglycemia. It’s also quite affordable.
But this traditional approach is changing. New medications continue to be FDA approved, and several of them are now prescribed as preferred treatments. They can be used along with — or in place of — metformin for certain people.
What are the best alternatives to metformin for Type 2 diabetes?
Many people with Type 2 diabetes find it difficult to hit their A1C and body weight goals. Heart failure, heart disease, or chronic kidney disease (CKD) can also be related issues. Certain medications have benefits over metformin in these scenarios.
1. GLP-1 agonists like Ozempic
Glucagon-like peptide-1 (GLP-1) agonists have been widely discussed in healthcare and news circles over the past few years. Common GLP-1 agonists for Type 2 diabetes include:
Ozempic (injectable semaglutide)
Rybelsus (oral semaglutide)
Trulicity (dulaglutide)
Victoza (liraglutide)
GLP-1 agonists like these can lower A1C by up to 1.5%, proving to be very effective. They’re now the preferred injectable medications over insulin.
And they have more than just glucose-lowering benefits. A GLP-1 agonist with proven heart benefits is a recommended metformin alternative if you have heart disease. They can also lower body weight by up to 15 lbs (7 kg), depending on the medication and dosage. In fact, some of them are approved specifically for weight loss. Examples include Wegovy (semaglutide) and Saxenda (liraglutide).
2. SGLT2 inhibitors like Jardiance
The most common sodium-glucose cotransporter-2 (SGLT2) inhibitors are Farxiga (dapagliflozin), Jardiance (empagliflozin), and Invokana (canagliflozin). SGLT2 inhibitors are oral pills that are taken once daily. They can lower A1C by up to 1% and reduce body weight by at least 4 lbs (2 kg).
If metformin alone isn’t enough, adding an SGLT2 inhibitor may help. An SGLT2 inhibitor may also be prescribed on its own as a preferred option. SGLT2 inhibitors come in combination tablets with metformin for convenience too. And an SGLT2 inhibitor with proven benefits, such as Jardiance, is preferred in people with a history of heart or kidney disease. Your heart and your kidneys are linked, and SGLT2 inhibitors can help protect both.
Metformin benefits: Discover the several surprising benefits of metformin that you may not know about.
Metformin side effects: Some side effects are common when taking metformin. Learn more about what you can expect while taking this medication.
Metformin vs. Ozempic (semaglutide): Learn about the differences between these two diabetes medications and when one may be a better fit for you than the other.
Foods to avoid with metformin: You’ve likely heard all about the importance of a diabetes-friendly diet. Dive into this refresher on foods to avoid if you have a prescription for metformin.
What’s next? Discover new treatments for Type 2 diabetes that may be coming in the future.
3. Mounjaro
Mounjaro (tirzepatide) is one of the newest metformin alternatives. It’s a once-weekly injection that comes in six doses.
It’s also the first medication of its type. Mounjaro is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 agonist. Mounjaro’s dual role makes it potentially more effective than using a GLP-1 agonist (like Ozempic) alone.
In the initial clinical trials that it was studied in, it lowered A1C by over 2% for some people and reduced body weight up to 25 lbs (11 kg) when used in combination with metformin. It reduced body weight by up to 17 lbs (8 kg) when used alone.
These are Mounjaro’s biggest strengths — how well it can lower A1C and body weight. It’s a preferred medication to consider, especially if losing weight is a priority. Zepbound (tirzepatide) contains the same active ingredient as Mounjaro. But it’s approved specifically for chronic weight management. Zepbound might be an option for weight loss regardless of whether you have diabetes.
4. Insulin
Insulin is a necessary treatment for people with Type 1 diabetes. But in certain cases, people with Type 2 diabetes may need to use insulin, too. This may be the case when your diabetes is more advanced. Insulin is also a good alternative if you have advanced kidney disease and can’t take metformin.
There are different types of insulin available depending on your needs, preferences, and health background. Insulin is available through an injection, an inhaler, or a continuous insulin pump. Talk to a healthcare professional about whether insulin is a good option for you.
5. DPP-4 inhibitors like Januvia
Dipeptidyl peptidase-4 (DPP-4) inhibitors, also known as gliptins, are other metformin alternatives. This class includes Januvia (sitagliptin), Tradjenta (linagliptin), and Nesina (alogliptin).
These once-daily oral pills lower A1C up to 0.8%, making them less effective than metformin in general. These medications are often used in combination with metformin if you are very close to your target A1C but need a bit more support.
DPP-4 inhibitors usually have mild side effects and a neutral effect on body weight. So if you can’t tolerate metformin, they may be a good option to use instead.
6. Thiazolidinediones like Actos
Actos (pioglitazone) is the only thiazolidinedione (also called a glitazone or TZD) currently available. Actos can lower A1C by around 1%. But it can add to weight gain, so it’s not generally a first-choice medication.
If metformin alone is not enough to reach your A1C goal, and other medications aren’t available or appropriate for your situation, adding a TZD, such as Actos might be an option.
7. Sulfonylureas like glipizide
Sulfonylureas are another group of diabetes medications. Common sulfonylureas include glipizide (Glucotrol XL), glyburide (Glynase, DiaBeta), and glimepiride (Amaryl).
These oral pills can lower A1C by about 1%, but they have a high risk of causing hypoglycemia. They may also lead to a modest amount of weight gain. Your prescriber will help decide if adding a sulfonylurea to your routine would be worthwhile.
8. Meglitinides
Meglitinides, also known as glinides, are another group of oral tablets for Type 2 diabetes. The two main ones are repaglinide and nateglinide. They work similarly to sulfonylureas and lower A1C by about 0.75%.
Glinides aren’t generally first-choice medications, though. This is because you have to take them several times a day with meals. They can also cause side effects such as low blood sugar and weight gain. A healthcare professional might sometimes recommend a glinide if your blood sugar rises too high after meals.
9. Alpha-glucosidase inhibitors
Alpha-glucosidase inhibitors are another group of oral diabetes medications. They include acarbose and miglitol, and they work by slowing down the breakdown of carbohydrates. On average, they can lower your A1C by up to 1%.
Alpha-glucosidase inhibitors don’t raise insulin levels. So they’re less likely to cause low blood sugar when used on its own. The most common side effects are gas, bloating, and stomach upset. This is especially the case when you first start the medication.
Generally speaking, healthcare professionals only prescribe acarbose or miglitol if other diabetes medications aren’t doing enough to keep your blood sugar in its target range.
10. Combination medications
Combination medications — those that are formulated with metformin and another oral medication — can be useful and convenient. If you don’t like the idea of taking multiple pills, a combination product can help simplify your daily medication regimen.
Several metformin combination products are available. For instance, the pairing of metformin and a DPP-4 inhibitor includes medications such as Janumet (sitagliptin / metformin) and Jentadueto (linagliptin / metformin). The combination of metformin with an SGLT2 inhibitor includes Synjardy (empagliflozin / metformin), Invokamet (canagliflozin / metformin), and Xigduo XR (dapagliflozin / metformin).
If you take these medications separately, switching to a combination medication can help. It helps lower the number of daily pills and makes doses more convenient. But, the most cost-effective choice can depend on your situation, specific medications, and insurance status.
Are there any natural alternatives to metformin?
There aren’t any natural alternatives, such as vitamins or supplements, that are approved to treat diabetes. Although certain natural products may be useful, they shouldn’t replace a prescription medication. As with routine exercise and a diabetes-friendly diet, they’re better to be used as a sidekick to your other medications.
If you’re interested in taking a vitamin or supplement to lower your blood sugar, talk with your pharmacist or prescriber. They can offer guidance on whether it’s safe to add to your routine. In some cases, they can lead to extra side effects or interactions.
Bariatric surgery (weight-loss surgery) may be an option if you have Type 2 diabetes and obesity. Weight-loss surgery changes the structure of your stomach or intestines to help you lose weight. This procedure might improve your blood sugar and could even lead to diabetes remission. But it’s important to note that weight-loss surgery isn’t for everyone. It can be costly, and it’s usually considered only when other treatment options haven’t been effective.
When should you talk to your healthcare professional about metformin alternatives?
Choosing the right medication isn’t simple. Metformin isn’t the best choice for everyone. You should talk to a healthcare professional about metformin alternatives if you:
Can’t tolerate metformin due to side effects
Can’t take metformin because your kidney function is low
Have other health conditions, such as a history of heart disease or heart failure
Are not meeting your blood sugar and A1C targets with metformin alone
Frequently asked questions
There’s no single best alternative to metformin. Many people benefit from GLP-1 agonists like Ozempic and SGLT2 inhibitors like Jardiance, but your prescriber will make the final call on the best alternative for you. This will likely be based on what you’d benefit most from, such as additional A1C support, heart protection, or body weight reduction. Your health insurance status may also play a role.
Lactic acidosis is a rare but serious metformin side effect. It happens when lactic acid builds up in your blood. It’s more common among older adults, those with kidney impairment, and excessive alcohol use. Possible symptoms of lactic acidosis include fatigue, confusion, and difficulty catching your breath. You may also feel pain in your stomach or have a fast heartbeat. Seek immediate medical attention if you think you’re experiencing lactic acidosis.
Metformin can be hard on your kidneys, but it doesn’t necessarily harm them. It more so poses an issue if your kidneys aren’t working as well as they could. Metformin can build up in your blood if your kidneys are having a hard time clearing it out. Rising metformin levels increases the risk of experiencing lactic acidosis, among other side effects.
Your prescriber will likely order blood tests to see how well your kidneys are working before you start metformin and routinely while you’re taking it.
There’s no single best alternative to metformin. Many people benefit from GLP-1 agonists like Ozempic and SGLT2 inhibitors like Jardiance, but your prescriber will make the final call on the best alternative for you. This will likely be based on what you’d benefit most from, such as additional A1C support, heart protection, or body weight reduction. Your health insurance status may also play a role.
Lactic acidosis is a rare but serious metformin side effect. It happens when lactic acid builds up in your blood. It’s more common among older adults, those with kidney impairment, and excessive alcohol use. Possible symptoms of lactic acidosis include fatigue, confusion, and difficulty catching your breath. You may also feel pain in your stomach or have a fast heartbeat. Seek immediate medical attention if you think you’re experiencing lactic acidosis.
Metformin can be hard on your kidneys, but it doesn’t necessarily harm them. It more so poses an issue if your kidneys aren’t working as well as they could. Metformin can build up in your blood if your kidneys are having a hard time clearing it out. Rising metformin levels increases the risk of experiencing lactic acidosis, among other side effects.
Your prescriber will likely order blood tests to see how well your kidneys are working before you start metformin and routinely while you’re taking it.
The bottom line
Several metformin alternatives for Type 2 diabetes are available. Sodium-glucose cotransporter-2 (SGLT2) inhibitors like Jardiance (empagliflozin), glucagon-like peptide-1 (GLP-1) agonists like Ozempic (semaglutide), and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists like Mounjaro (tirzepatide) are all preferred options. The best choice hinges on your individual needs. Such as, if you’re aiming for heart health benefits, weight loss, or improved A1C levels. Ask a healthcare professional if a metformin alternative is right for you.
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References
American Diabetes Association. (n.d.). Use of glucose-lowering medications in the management of type 2 diabetes.
American Diabetes Association. (n.d.). Vitamins, minerals, and supplements.
American Diabetes Association Professional Practice Committee. (2024). Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes—2025. Diabetes Care.
Blonde, L., et al. (2022). American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a diabetes mellitus comprehensive care plan—2022 update. Endocrine Practice.
Chumakova-Orin, M., et al. (2021). Diabetes remission after bariatric surgery. World Journal of Diabetes.
Eli Lilly and Company. (2022). FDA approves Lilly's mounjaro (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes.
Hirst, J. A., et al. (2013). Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia.
Holst, J. J. (2019). The incretin system in healthy humans: The role of GIP and GLP-1. Metabolism - Clinical and Experimental.
Lebovitz, H. E. (1997). Alpha-Glucosidase inhibitors. Endocrinology and Metabolism Clinics of North America.
Marx, N., et al. (2022). GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with Type 2 diabetes. Circulation.
National Institutes of Health. (2024). Weight-loss surgery yields long-term benefits for type 2 diabetes.
Sanchez-Rangel, E., et al. (2017). Metformin: Clinical use in Type 2 diabetes. Diabetologia.
Sherifali, D., et al. (2010). The effect of oral antidiabetic agents on A1C levels: A systematic review and meta-analysis. Diabetes Care.
Zurek, A. M., et al. (2017). A review of the efficacy and safety of sodium–glucose cotransporter 2 inhibitors: A focus on diabetic ketoacidosis. Diabetes Spectrum.
