6 Metformin Alternatives to Consider for Type 2 Diabetes

Key Takeaways

Metformin is a first-line treatment for type 2 diabetes mellitus. However, taking metformin alone does not always adequately control blood sugar levels, and additional medications are required.
If metformin is not sufficient, your healthcare provider may prescribe SGLT-2 inhibitors or GLP-1 receptor agonists. The diabetes treatment prescribed depends on your age, severity of diabetes, and other comorbidities.
One of the newest diabetes treatments is an injectable medication called tirzepatide (Mounjaro), which has been FDA-approved for chronic weight management.

Diabetes, a chronic health condition that causes excess glucose in the blood, can increase the risk of many health complications over time. Traditionally, metformin (brand name Glucophage) is a first-line treatment for people with type 2 diabetes mellitus.

It belongs to a group of drugs called biguanides and is one of the most commonly prescribed oral medications for diabetes due to its low cost and safety profile. Metformin helps to lower blood glucose levels by decreasing glucose production in the liver while reducing its absorption in the stomach and intestines. In addition, metformin also increases insulin sensitivity of fat cells and muscle tissue.

There is no doubt about the role of metformin in diabetes treatment. However, metformin is known to cause gastrointestinal (GI) side effects, causing stomach upset, nausea, and diarrhea. As a result of these GI side effects, many people cannot tolerate metformin, and having other alternatives to metformin is essential.

Besides unpleasant side effects, for many people, taking metformin alone does not adequately control blood sugar levels, and additional medications are required for diabetes management. The good news is that there are different types of medications with different mechanisms of action that can be used in combination to effectively treat diabetes.

Please keep reading to learn about some common metformin alternatives.

What can I take for type 2 diabetes instead of metformin?

Sulfonylureas

These are some of the oldest oral diabetes medicines. They are taken by mouth once or twice a day before meals.

Sulfonylureas increase insulin production by beta cells in the pancreas. Common side effects include weight gain and low blood sugar. Examples of sulfonylureas are glimepiride (Amaryl), glyburide (Glynase and Diabeta), and glipizide (Glucotrol and Glucotrol XL).

SGLT-2 Inhibitors

Sodium-glucose cotransporter-2 (SGLT2) inhibitors is a group of oral diabetes medicines that help with glucose control by preventing sugar reabsorption by the kidney then facilitating the extra sugar via the urine.

They are associated with a low risk of severe hypoglycemia (low blood sugar). These medicines protect against kidney disease, heart disease, and heart failure.

Common side effects include urinary frequency and genital yeast infections. Examples of SGLT-2 inhibitors are empagliflozin (Jardiance), bexagliflozin (Brenzavvy), dapagliflozin (Farxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro).

GLP-1 Receptor Agonists

Glucagon-like peptide-1 (GLP-1) agonists are available as oral medication to be taken once daily or as injectable medications that are taken daily or weekly. They help to lower blood glucose levels and can lead to significant weight loss. Notably, some GLP-1 agonists have also been shown to be beneficial for your heart and kidneys. Therefore, GLP-1 agonists are a good alternative to treat diabetes if you also have heart disease.

GLP-1 receptor agonists trigger insulin release by the pancreas and block the hormone glucagon, which raises blood glucose, slows down gastric emptying, and increases satiety after meals.

Common side effects include gastrointestinal problems like nausea, vomiting, diarrhea, and loss of appetite.

Due to their weight loss effects, Wegovy (semaglutide) and Saxenda (liraglutide) are approved by the U.S Food and Drug Administration (FDA) for weight management.

Examples of GLP-1 receptor agonists are semaglutide injection (Ozempic), oral semaglutide tablets (Rybelsus), liraglutide (Victoza), dulaglutide (Trulicity), exenatide (Byetta), extended release exenatide (Bydureon), and lixisenatide (Adlyxin).

DPP-4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) inhibitors is a group of anti-diabetes drugs that are taken by mouth once daily, before or after meals. They prevent the breakdown of natural hormones that lower blood glucose levels. DPP-4 inhibitors are also known as “gliptins.”

This helps to lower hemoglobin A1C (average blood sugar levels over the past 2-3 months). DPP-4 inhibitors are generally well tolerated and are less likely to cause hypoglycemia (low blood sugar). DPP-4 inhibitors are considered to be weight-neutral, meaning agents from this drug class don't cause any weight gain or weight loss.

Common side effects include headache, upset stomach, and flu-like symptoms.

Examples of DPP-4 inhibitors are sitagliptin (Januvia), linagliptin (Tradjenta), alogliptin (Nesina), and saxagliptin (Onglyza).

Thiazolidinediones (TZDs)

These are oral drugs that reduce insulin resistance and increase insulin sensitivity of muscle and fat cells. Lower-cost generic drugs are available for drugs in this class. However, their side effect profile, especially with the increased risk of heart failure, is one of the disadvantages of TZDs. However, they can cause weight gain, edema (fluid retention), and an increased risk of heart failure.

Thiazolidinediones are also referred to as “TZDs” or “glitazone.”

Examples are rosiglitazone (Avandia) and pioglitazone (Actos).

Other medications for diabetes management

Alpha glucosidase inhibitors such as miglitol (Glyset) and Acarbose (Precose)
Bile acid sequestrants such as colesevelam (Welchol) to be used in combination with other diabetes medications
Dopamine-2 agonists such as bromocriptine (Cycloset)
Meglitinides such as repaglinide (Prandin) and nateglinide (Starlix)

Insulin

Insulin is the most effective medication to control high blood sugar levels.

If diet and lifestyle changes, along with oral diabetes medications or non-insulin injectable diabetes medications, do not adequately lower blood sugar levels, your healthcare provider may recommend starting insulin.

Insulin is also used to treat complications such as diabetic ketoacidosis. The disadvantage of insulin is that it must be injected.

What is the next best diabetes medication after metformin?

If your diabetes is uncontrolled on metformin or you cannot take metformin, your healthcare provider may prescribe alternatives to metformin, such as SGLT-2 inhibitors or GLP-1 receptor agonists.

The best diabetes medication may be different for everyone. The factors that are taken into consideration when deciding the best approach for diabetes treatment are:

Age
Severity of diabetes
Other comorbidities such as heart disease, kidney disease, and obesity

What are doctors prescribing instead of metformin?

There are many treatment options for type 2 diabetes. Doctors choose a medication to treat diabetes based on many factors, such as your initial hemoglobin A1c, the duration of your diabetes, physical findings, coexisting medical conditions such as high cholesterol, kidney function, or cardiovascular disease, cost of diabetes care, insurance coverage, and your personal preferences.

Many metformin alternatives are available, and they work differently. Your provider may choose a metformin alternative, or they may prescribe metformin along with other drugs to lower glucose levels to a healthy range and achieve glycemic control and overall health goals.

Remember, lifestyle modifications are natural alternatives to drugs and can help you lose weight and control blood glucose levels.

What is the new pill for type 2 diabetes in 2023?

One of the newest therapies for type 2 diabetes is an injectable medication called tirzepatide (Mounjaro). It is a dual GIP and GLP-1 receptor agonist. Injectable tirzepatide (under the brand name Zepbound) has been FDA-approved for chronic weight management.

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