Metformin vs Alternative Diabetes Drugs

If you can’t manage your diabetes with lifestyle alone, your doctor will likely advise you to start taking medication to control your blood glucose levels. 

Metformin is one of the most commonly prescribed medications for type 2 diabetes, while insulin is often the only medication used for type 1 diabetes

There are several metformin alternatives, and it can be difficult to decide which medication to take.

How do you know if metformin is best for you or if it’s time to try another diabetes medication?

What is metformin?

One of the most commonly prescribed medications for type 2 diabetes is metformin. Metformin is the generic name most widely prescribed, and the brand name for metformin is Glucophage.

Metformin doesn’t cause low blood sugar (hypoglycemia), which is one of its major benefits and a reason it’s often prescribed as the first diabetes medication for patients with type 2 diabetes. Because it doesn’t cause low blood sugar, people with type 2 diabetes can take metformin with other medications like sulfonylureas and injectable insulin.

Metformin is in a drug class called biguanides. Biguanides help reduce the amount of sugar your liver makes while improving insulin sensitivity, which helps reduce high blood sugar. There are two types of metformin – regular and extended-release (XR).

The common dosage for metformin ranges from 500 milligrams to a maximum of 2,550 milligrams per day. It’s usually recommended to split the dose among meals, typically three times per day. 

While metformin is most commonly used for type 2 diabetes, it’s also used to help treat polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is a hormonal disorder in women often stemming from insulin resistance

RELATED: Metformin Diet: 5 Foods To Eat and 6 You Should Avoid.

3 benefits of metformin for diabetes

1. No hypoglycemia

Metformin acts by reducing the amount of glucose (sugar) produced by your liver and helps your cells be more sensitive to insulin. 

Unlike other types of diabetes medication, metformin doesn’t cause low blood sugar. Because it won’t cause hypoglycemia, you can use it in addition to other medications, including injectable insulin.

2. Oral form instead of an injection

Many people with diabetes are hesitant to take medication that requires an injection. Metformin is only in pill form, so it doesn’t require injections.

3. Financial considerations

Metformin is much more affordable than some of the newer types of diabetes medications available today. Choosing the generic brand will be even more cost-effective.

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Side effects and risks of metformin

The most common metformin side effects are gastrointestinal-related. 

If you start taking metformin, you may experience some of these side effects:

Metformin might also reduce your body’s ability to absorb vitamin B12 in your stomach. Approximately 6-30% of people taking metformin experience vitamin B12 deficiency. According to studies, the higher the metformin dose, the greater the risk of vitamin B12 deficiency. 

Vitamin B12 is important for creating DNA and red blood cells. Vitamin B12 deficiency can lead to anemia, which is when you have lower levels of red blood cells than is healthy. Anemia from vitamin B12 deficiency is pernicious anemia. 

It comes with symptoms such as:

  • Weakness, tiredness, or lightheadedness
  • Heart palpitations and shortness of breath
  • Pale skin
  • A smooth tongue
  • Constipation, diarrhea, loss of appetite, or gas 
  • Nerve problems like numbness or tingling, muscle weakness, and problems walking
  • Vision loss
  • Mental symptoms like depression, memory loss, or behavioral changes

You often treat a vitamin B12 deficiency with vitamin B12 injections. Oral supplements aren’t usually used to treat pernicious anemia because the issue lies in the stomach’s ability to absorb vitamin B12.

Most people taking metformin experience minor side effects. However, there is a low risk of more severe side effects from taking metformin. Lactic acidosis is a serious condition where your body creates more lactic acid than your body can clear. 

The symptoms of lactic acidosis usually set in quickly and include:

  • Abdominal or stomach discomfort
  • Decreased appetite
  • Diarrhea
  • Fast, shallow breathing
  • Discomfort
  • Muscle pain or cramping
  • Unusual sleepiness, tiredness, or weakness

Metformin overdose is the main risk factor for developing lactic acidosis

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Reasons people may stop taking metformin

You might stop taking metformin if the side effects are interfering with your life or causing you distress. Metformin impacts everyone differently, so it’s impossible to predict who will have little to no side effects and who will have severe side effects.

If your blood sugar levels are no longer well-controlled on metformin and metformin isn’t working for you anymore, your provider may recommend some metformin alternatives to add to your metformin or to use without metformin.

You might also consider stopping metformin if you’re reaching your blood glucose targets. Some people can manage their blood sugar levels with lifestyle alone and may no longer need metformin. Patients who undergo weight loss surgery and lose a significant amount of weight can often stop some medications such as metformin.

The glomerular filtration rate (GFR) is an indicator of how efficiently your kidneys filter blood. Metformin is safe to use when the estimated GFR is greater than or equal to 45 milliliters per minute. This means you might need to stop taking metformin if your kidney function declines or if you have advanced kidney disease.

RELATED: What Happens When You Stop Taking Metformin for Diabetes?

Metformin vs other diabetes medications 


Diabetics can use sulfonylureas in addition to metformin. They are a popular second medication choice in addition to metformin since they can help lower blood glucose even more without needing to start injectable medications.

Sulfonylureas work by helping your pancreas secrete more insulin. Because they help increase insulin levels, sulfonylureas can cause low blood sugar.

Some popular sulfonylureas include glipizide, glyburide, and glimepiride. 

Pros of sulfonylureas

  • Can take it along with metformin to help lower A1c
  • Non-injectable medication
  • High blood-sugar-lowering ability

Cons of sulfonylureas

  • Risk for low blood sugar
  • May cause weight gain
  • Might not be enough to manage blood sugar over time 

GLP-1 receptor agonists

Glucagon-like peptide (GLP)-1 is a hormone that increases insulin secretion after eating, helping to lower blood sugar levels. GLP-1 receptor agonists are drugs that help increase the amount of insulin secreted after eating by mimicking GLP-1. They come in the form of an injection.

GLP-1 receptor agonists’ drug names end in -ide, such as exenatide (Byetta), liraglutide (Victoza), and dulaglutide (Trulicity). You inject them under the skin as often as twice per day or as little as once per week depending on the drug used and the response. GLP-1 receptor agonists don’t usually cause low blood sugar on their own.

Pros of GLP-1 receptor agonists

  • Potential for non-daily dosing, improving adherence to schedule
  • Doesn’t cause low blood sugar
  • May result in weight loss

Cons of GLP-1 receptor agonists

  • Injectible, which some patients don’t prefer
  • Potential gastrointestinal side effects such as nausea
  • More expensive than many oral diabetes meds

DPP-4 inhibitors

Dipeptidyl peptidase 4 (DPP-4) is an enzyme that destroys a type of hormone called incretins. Incretins help your body produce more insulin when it’s needed but also tell the liver to release less sugar when it’s not required. 

DPP-4 inhibitors block the action of DPP-4, helping to increase insulin secretion and better regulate blood sugar levels.

DPP-4 inhibitors’ drug names end in -liptin such as sitagliptin (Januvia) and saxagliptin (Onglyza). They can also be combined with other medications like metformin and sitagliptin/Januvia (Janumet). DPP-4 inhibitors don’t cause low blood sugar.

Pros of DPP-4 inhibitors

  • Once-a-day dosing versus multiple times per day
  • Doesn’t cause low blood sugar
  • Weight neutral (shouldn’t cause weight gain)
  • May help slow the progression of kidney disease

Cons of DPP-4 inhibitors

  • Injectible, which some patients don’t prefer
  • Potential gastrointestinal side effects such as nausea
  • More expensive than many oral diabetes meds
  • Lower blood-sugar-lowering ability than other DM medications like metformin and GLP-1 receptor agonists

SGLT2 inhibitors

SGLT2 inhibitors canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) help increase the amount of sugar excreted in your urine by your kidneys. 

These medications are a bit newer and were FDA-approved in 2013 for the treatment of diabetes. Another benefit of these medications is that they can help promote weight loss, which can improve blood sugar levels if you have diabetes and are overweight or obese. SGLT-2 inhibitors may help reduce the risk of cardiovascular disease, including heart disease.

Some of the potential side effects of SGLT2 inhibitors include increased yeast infections and urinary tract infections from the extra glucose in the urine. 

Pros of SGLT2 inhibitors

  • Doesn’t cause low blood sugar
  • Weight neutral (shouldn’t cause weight gain)
  • High ability to lower blood sugar levels
  • Once-a-day, oral dosage
  • May help lower cardiovascular disease risk

Cons of SGLT2 inhibitors

  • Potential for increased urinary tract infections (UTI)
  • More expensive than many oral diabetes meds
  • Can increase LDL (bad) cholesterol

Thiazolidinediones (TZDs) 

TZDs help lower blood glucose by improving insulin sensitivity. They aren’t used very often due to their side effects and potential complications. 

TZDs can cause fluid retention and weight gain, which can worsen health conditions like congestive heart failure, kidney disease, or liver problems.

Pros of TZDs

  • Improves insulin sensitivity
  • Oral route

Cons of TZDs

  • Can cause weight gain and edema
  • Might increase your risk of heart failure and bone fractures


Glinides help the pancreas produce more insulin, helping to lower blood sugars. They are to be taken within 15-30 minutes of a meal.

Glinides have a short action time (the time it takes for the medication to start lowering your blood sugar) and carry a risk of low blood sugar, but can be safe options for some people. Some examples of glinides are Prandin and Starlix.

Pros of glinides

  • Increases insulin production
  • Oral route

Cons of glinides

  • Higher risk of low blood sugar
  • Can cause weight gain


Insulin is the most efficient medication for treating diabetes since it mimics your body’s ability to lower blood sugar levels. There are several types of insulin, and some can be combined to tailor to each patient’s individual needs.

Insulin is the primary medication to treat type 1 diabetes, which occurs when the insulin-producing cells (beta cells) in the pancreas are mistakenly destroyed by your immune system.

Pros of insulin

  • Little side effects other than low blood sugar
  • Effective at lowering blood sugar

Cons of insulin

  • Higher risk of low blood sugar
  • Primarily injectible, which some patients don’t prefer

RELATED: Medications to Avoid While Taking Metformin.

Can you take metformin with other diabetes medications?

One of the benefits of metformin is that you can take it with almost all of the other diabetes medications. If your blood sugar is well-controlled after starting a new medication in addition to metformin, you might prefer to stop taking metformin to simplify your medication regimen.

Metformin is so compatible that it’s combined with several other diabetes medications for a two-in-one medication, such as JanuMet (Januvia + metformin), Invokamet (Invokana + metformin), and others.

You should always speak with your healthcare provider and pharmacist about the compatibility of your diabetes medications. Side effects may vary depending on the types of medication you’re taking.

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Things to consider when choosing a diabetes medication

Several factors come into play when determining which diabetes medication you should choose. Your healthcare provider can guide you in your decision based on your medical history, other health conditions, diabetes duration, blood glucose control, lifestyle factors, any budgetary constraints, and other considerations.


Metformin is the most commonly prescribed medication for type 2 diabetes. Patients can use metformin in addition to several other alternatives for diabetes medications, including insulin. 

There are several metformin alternatives if you don’t tolerate metformin well, or if you’re not reaching your blood sugar goals on metformin.

There are potential side effects, pros, and cons associated with all types of medication. Therefore, you should work with a trusted healthcare provider to choose which types of medication are best for you, your health history, and your lifestyle.

Explore More

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Natural Alternatives to Metformin for Diabetes & Insulin Resistance.


  1. Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010. 
  2. Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore). 2019. 
  3. Hur KY, Kim MK, Ko SH, et al. Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement. Diabetes Metab J. 2020. 
  4. [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Medication for type 2 diabetes. [Updated 2020 Oct 22].

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