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The Best Alternatives to Metformin for Type 2 Diabetes Management

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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) orally, in the form of a pill. It’s in a class of drugs called biguanides. 

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

For the vast majority of people, these side effects abate over time, but for some people, they do not. For other people, Metformin simply isn’t effective and alternatives are needed for type 2 diabetes management. 

This article will investigate the best alternatives to Metformin for type 2 diabetes patients. 

Package of Metformin tablets with a red cross in front

Why would people not take Metformin?

Metformin is extremely cheap and effective at helping people better manage their blood sugar levels, but that effectiveness comes with a cost. 

Metformin can cause strong side effects that may be detrimental to some people who take it, including chronic diarrhea, stomach aches and cramps, nausea, and even vomiting. 

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

Additionally, these side effects can also hurt other areas of your life, such as becoming an obstacle to eating properly for your diabetes or preventing you from being able to maintain a regular exercise habit. 

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

Sometimes it’s impossible to stop taking another drug that negatively interacts with Metformin, and therefore, a substitute is necessary. 

Additionally, for some patients, Metformin just simply is not effective. It does not help everyone better manage their blood sugars, lower their HbA1c levels, or lose weight. In fact, some people even gain weight when taking Metformin! 

Finally, some people may opt to not take Metformin because their health insurance doesn’t cover it, or they wish to manage their diabetes without the use of pharmaceuticals. 

What are alternatives to Metformin? 

If for some reason you don’t wish to start treatment with Metformin, or it isn’t working properly for you, or you’re experiencing too severe side effects, the following are the best alternatives that you should talk with 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 medication used to lower blood sugar levels (and HbA1c levels) by releasing excess glucose through the urinary tract. 

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

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

Possible side effects include:

  • Frequent urination
  • Increased frequency of UTIs 
  • Increased risk for kidney damage
  • Increased risk for diabetic ketoacidosis (DKA)
  • Dehydration
  • Thirst
  • Low blood pressure 
  • Invokana, specifically, increases the risk of amputations 

GLP-1 Receptor Agonists 

GLP-1 receptor agonists are another option if Metformin isn’t working for you. These can either be taken orally or through an injection (either once a day or once weekly). 

They are proven to lower blood sugar levels and HbA1c levels, as well as protect against kidney disease and heart disease as well. 

Most notably, GLP-1 receptor agonists can aid in significant weight loss. According to the Mayo Clinic, all GLP-1 drugs can lead to a total weight loss of between 10.5-15.8 pounds. 

Available brand names include Bydureon, Byetta, Ozempic, Adlyxin, Rybelsus, Trulicity, and Victoza.

Possible side effects include: 

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

Sulfonylureas (SFUs)

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

Sulfonylureas are oral medications that are generally taken with or before a meal. The medication is usually taken once a day before breakfast, or twice daily, before both breakfast and dinner. 

Possible side effects include: 

  • Hypoglycemia (low blood sugar) 
  • Weight gain 
  • Hunger 
  • GI issues, like upset stomach 

DPP-4 Inhibitors 

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

These drugs are taken orally, typically in combination with Metformin, but can be taken without Metformin as well. 

DPP-4 inhibitors do not aid in weight loss, nor offer heart disease and kidney disease protection like other type 2 diabetes drugs. 

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

Possible side effects include:

  • Low blood sugar, if taken in conjunction with insulin 
  • GI issues, like upset stomach 
  • Increased risk for pancreatitis 
  • Fever, body achse, and other flu-like symptoms 

Thiazolidinediones (TZDs)

TZDs are an oral class of type 2 diabetes medication that increases insulin sensitivity that helps reduce insulin resistance. 

They do not aid in weight loss, and offer no protective benefits against heart disease. They are easily accessible and affordable. 

Possible side effects include:

  • Weight gain
  • Increased risk for heart disease
  • Edema of feet, legs, arms, and hands 
  • Increased risk for bone fracture 

Lifestyle changes 

Finally, if you wish to not take additional medications, you can increase your levels of physical activity, and change your diet to help manage blood sugar levels, lower your HbA1c, and potentially lose weight. 

This may be the cheapest option, but can be hard to maintain. It’s also not guaranteed that lifestyle changes will allow you to stop taking medications. 

Other factors, such as a genetic predisposition for diabetes, can make medication necessary, even if you are in great physical condition and otherwise healthy.  

Talk with your doctor and meet with a registered dietitian to develop an exercise and eating plan that will work for your lifestyle and health goals. 


While Metformin is an extremely popular, affordable, and accessible drug for type 2 diabetes management, it is not for everyone. 

Many people experience debilitating side effects that make taking this drug in the long term impossible. Others may not have insurance coverage for Metformin, or the drug may simply not be working for them. 

Some people may wish to not take additional pharmaceutical drugs. Fortunately, other options are available. 

Prescription drugs such as GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones, and even implementing diet and exercise lifestyle changes can work to manage your blood sugar and HbA1c levels, to improve your type 2 diabetes management. 

Some of these drugs are available in generics, however, SGLT-2 inhibitors and GLP-1 receptor agonists do not yet have generics, making them more expensive and perhaps cost-prohibitive to some patients. 

Do some research to see what your health insurance will cover, to make sure that any changes in your diabetes medications are sustainable over the long term. 

If you’re struggling with Metformin, and want to make a switch, talk with your doctor about possible alternatives, and see what will work best for you, your lifestyle, and your health goals. 


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