The best alternatives to metformin for treating type 2 diabetes

Metformin is a popular prescription drug that is used as a first-line treatment for type 2 diabetes.

It is taken daily (or twice daily) by mouth, in pill form. It belongs to a class of drugs called biguanides.

Metformin helps people better control their blood sugar levels, fight insulin resistance, and can even help people lose weight, although it has potential side effects.

For the vast majority of people, these side effects go away over time, but for some, they don’t. For others, metformin simply isn’t effective and alternatives are needed to treat type 2 diabetes.

In this article, we will explore the best metformin alternatives for type 2 diabetes patients.

Why shouldn’t people take metformin?

Metformin is extremely cheap and effective at helping people better control their blood sugar, but this effectiveness comes at a cost.

Metformin can cause severe side effects that can be harmful to some people who take it, including chronic diarrhoea, stomach aches and cramps, nausea, and even vomiting.

For some people who have prohibitive work or school schedules, it may not be possible to endure these side effects.

In addition, these side effects can also harm other areas of your life, such as becoming an obstacle to eating right if you have diabetes or preventing you from maintaining a regular exercise habit.

Other times, people may avoid taking metformin because it is contraindicated with many common prescription drugs. The Mayo Clinic lists medications that may interact negatively with metformin.

Sometimes it is impossible to stop another drug that negatively interacts with Metformin, so a replacement is necessary.

Additionally, for some patients, metformin simply isn’t effective. It doesn’t help everyone manage their blood sugar better, lower their HbA1c, or lose weight. In fact, some people even gain weight while taking metformin!

Finally, some people may choose not to take metformin because their health insurance does not cover it, or because they want to control their diabetes without the use of pharmaceuticals.

What are the alternatives to metformin?

If for some reason you don’t want to start metformin, or if it’s not working properly for you or you’re experiencing side effects that are too severe, below are the best alternatives you should talk to your doctor about.

Always work with your doctor before making any changes to your diabetes management.

SGLT-2 inhibitors

SGLT-2 inhibitors are a class of oral medications used to lower blood sugar (and HbA1c levels) by releasing excess glucose through the urinary tract.

These drugs can protect against heart disease and heart failure, however, they can be hard on the kidneys, so they are not recommended for people with kidney disease.

SGLT-2 inhibitors rarely cause low blood sugar. Current branded SLGT-2 inhibitors include: Invokana, Farxiga, Jardiance, and Steglatro.

Possible side effects include:

  • Frequent urination
  • Increased frequency of UTIs
  • Increased risk of kidney damage
  • Increased risk of diabetic ketoacidosis (DKA)
  • Dehydration
  • Desire
  • Low blood pressure
  • Invokana in particular increases the risk of amputation

GLP-1 receptor agonists

GLP-1 receptor agonists are another option if metformin isn’t working for you. They can be taken by mouth or by injection (once a day or once a week).

They have been proven to lower blood sugar and HbA1c levels, and protect against kidney and heart disease.

First of all, GLP-1 receptor agonists can help with significant weight loss. According to the Mayo Clinic, all GLP-1 drugs can lead to a total weight loss of 10.5 to 15.8 pounds.

Brands available include Bydureon, Byetta, Ozempic, Adlyxin, Rybelsus, Trulicity and Victoza.

Possible side effects include:

  • Nausea
  • Vomiting
  • Low blood sugar (if taken in combination with insulin)
  • Decreased need for insulin during insulin therapy
  • Diarrhea
  • Weight loss

Sulfonylureas (SFU)

SFUs can help lower blood glucose and HbA1c, but can cause hypoglycemia and weight gain.

Sulfonylureas are oral medications that are usually taken with or before food. The drug is usually taken once a day before breakfast or twice a day, before breakfast and dinner.

Possible side effects include:

  • Hypoglycemia (low blood sugar)
  • Gaining weight
  • Hunger
  • Gastrointestinal problems such as an upset stomach

DPP-4 inhibitors

DPP-4 inhibitors lower blood sugar and HbA1c by stopping glucagon production in the liver and stimulating insulin production in the pancreas. They also make you feel fuller by slowing down digestion.

These drugs are taken by mouth, usually in combination with metformin, but can also be taken without metformin.

DPP-4 inhibitors do not help with weight loss or provide protection against heart and kidney disease like other type 2 diabetes medications.

Available brands of DPP-4 inhibitors include Tradjenta, Onglyza, Nesina and Januvia.

Possible side effects include:

  • Low blood sugar if taken in combination with insulin
  • Gastrointestinal problems such as an upset stomach
  • Increased risk of pancreatitis
  • Fever, body aches and other flu-like symptoms

Thiazolidinediones (TZD)

TZDs are an oral class of type 2 diabetes medications that increase insulin sensitivity, which helps reduce insulin resistance.

They do not help with weight loss and offer no protection against heart disease. They are readily available and inexpensive.

Possible side effects include:

  • Gaining weight
  • Increased risk of heart disease
  • Swelling of the feet, legs, arms and hands
  • Increased risk of bone fractures

Lifestyle changes

Finally, if you don’t want to take additional medications, you can increase your physical activity levels and change your diet to help control your blood sugar, lower your HbA1c, and potentially lose weight.

This may be the cheapest option, but it can be difficult to maintain. There is also no guarantee that lifestyle changes will get you off your medication.

Other factors, such as a genetic predisposition to diabetes, may make medication necessary even if you are in great physical shape and otherwise healthy.

Talk to your doctor and meet with a registered dietitian to develop an exercise and nutrition plan that fits your lifestyle and health goals.


While metformin is an extremely popular, affordable, and accessible drug for treating type 2 diabetes, it’s not for everyone.

Many people experience debilitating side effects that prevent them from taking this drug in the long term. Others may not have coverage for Metformin, or the drug may just not work for them.

Some people may not want to take additional pharmaceutical medications. Fortunately, other options are available.

Prescription medications such as GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones, and even making changes to your diet and exercise can help control your blood sugar and HbA1c levels to improve treatment type 2 diabetes.

Some of these drugs are available as generics, however, SGLT-2 inhibitors and GLP-1 receptor agonists are not yet generic, making them more expensive and possibly unaffordable for some patients.

Do your research to see what your health insurance will cover to make sure any changes to your diabetes medications are permanent in the long term.

If you struggle with Metformin and want to make a change, talk to your doctor about possible alternatives and see what works best for you, your lifestyle, and your health goals.

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