What Is the First-Line Treatment for Type 2 Diabetes?

Adjusting your diet and exercising more are usually the first steps to controlling type 2 diabetes. If you still cannot maintain your target blood sugar, your healthcare provider may prescribe medication. Metformin is typically the first-line treatment.

This article discusses metformin, its side effects, and alternative medications used if metformin isn’t an option.

Woman talking to doctor

FatCamera / Getty Images

Why Is Metformin the First Choice?

Metformin belongs to a class of medications known as biguanides. It works by controlling blood sugar levels by reducing how much sugar gets absorbed from the food you eat into your system. It also decreases how much sugar is produced by the liver.

The drug was made a first-line therapy because of its ability to lower glucose (sugar) levels in the body, encourage weight loss, and reduce the risk for certain diabetes complications, such as vascular disease, which affects blood vessels. The risk of developing too-low blood sugar, often associated with other types of medication for diabetes, is also less a factor when taking metformin.

What is a Biguanide?

A biguanide is any medication that hinders the liver’s ability to produce glucose and the body’s ability to pick up glucose from food. These medications are also known for their cholesterol-lowering properties.

Side Effects and Contraindications

While metformin is generally considered safe, some known and common side effects are associated with the medication, including:

  • Stomach discomfort such as bloating, gas, indigestion, heartburn, or pain
  • Diarrhea and constipation
  • Metallic taste in the mouth
  • Headaches
  • Skin flushing (redness)
  • Muscle pains
  • Nail changes

Some health conditions and lifestyle factors may prevent a person from being able to take metformin. They include:

  • Kidney or liver problems
  • Uncontrolled diabetes
  • Severe infection
  • Recent heart attack or current ongoing treatment for heart failure
  • Breathing difficulties
  • High alcohol consumption or alcoholism
  • Circulation issues
  • An upcoming surgery that will require anesthesia or any scan or X-ray procedure that requires the use of a dye

People taking certain medications should also avoid metformin or speak to their healthcare provider before starting metformin therapy. Some drugs that may interact with metformin include:

  • Steroids
  • Diuretics (water pills)
  • Blood pressure medications
  • Hormone drugs such as estrogen, progesterone, or birth control pills
  • Other diabetic medications
  • Antinausea drugs
  • Asthma medications
  • Medications designed to treat mental health conditions
  • Thyroid disease drugs

Metformin may also reduce vitamin B12 levels in the body, so healthcare providers should monitor your B12 stores and have you supplement if necessary when taking the drug. Vitamin B12 is essential for nerve cells and blood health.

Severe Metformin Side Effects

Some severe side effects, such as a rash or chest pain, are rare but can occur while taking metformin. Lactic acidosis, a severe and life-threatening condition, may also be caused by metformin use. Drinking large amounts of alcohol or taking certain medications such as Diamox (acetazolamide), Keveyis (diclofenamide), Topamax (topiramate), or Zonegran (zonisamide) can increase the risk of lactic acidosis.  

Medication Prescribed With Metformin

Metformin is often prescribed with other medications or as a combination medicine to help control diabetes further. Some medications that can be prescribed with metformin include:

  • Thiazolidinediones: Medications such as Actos (pioglitazone) and Avandia (rosiglitazone) increase the body’s ability to use insulin and can be prescribed alongside metformin.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors: Medications such as Invokana (canagliflozin), Xigduo (dapagliflozin), and Glyxambi (empagliflozin) reduce the kidneys' ability to reabsorb sugar from urine, thus, reducing blood sugar.
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors: Medications such as Janumet (sitagliptin), Kombiglyze (saxagliptin), Jentadueto (linagliptin), and Kazano (alogliptin) work by blocking an enzyme from destroying the hormone glucagon-like peptide 1 (GLP1). GLP1is used by the body to produce or reduce insulin as needed. When the body destroys this hormone, insulin production becomes imbalanced and can worsen diabetes.

Metformin may also be used alongside other therapies for diabetes, such as insulin therapy, to help better manage the disease when insulin alone is no longer working as it should.

What are Combination Medications?

Combination medications are usually two drugs in one dose. For example, if a person takes an oral pill for their health condition, it will contain two drugs in one pill. Many diabetes medications are considered combination pills, with Metformin being one of the two drugs in many of them.


Metformin is a first-line therapy because of its effectiveness and safety. Typically, people who take metformin alongside lifestyle changes such as eating healthier and exercising more can manage their diabetes effectively.

Metformin for Diabetes Prevention

In some cases, metformin has been used to prevent the onset of diabetes in people at a higher risk of developing the condition. Research has found that using metformin, along with lifestyle interventions, as a preventative technique can cut the risk of diabetes in half.

Alternative Medications

While metformin is the most commonly used medication for diabetes, it isn’t the only option. Many other drugs are used to manage the condition. The type of drug used depends on the personal factors of each person with type 2 diabetes.

The drugs mentioned above (thiazolidinediones, SGLT2 inhibitors, and DPP-4 inhibitors) are also options for people who cannot take metformin. Medications that encourage better insulin production may also be used and include sulfonylureas and glinides.

Insulin for Type 2 Diabetes

Insulin isn’t always needed for people with type 2 diabetes and is often reserved for those with type 1. People with type 2 diabetes that have tried other medications but haven’t seen any change in their condition are often good candidates for insulin.

Why Isn't Insulin Always Needed for Type 2 Diabetes?

Type 1 and type 2 diabetes differ. Type 1 diabetes develops when the pancreas, the organ that creates the hormone insulin, doesn’t produce enough to help the body manage blood sugar levels. Type 2 diabetes is more likely to occur when the body does not use the insulin created by the pancreas as well as it should. There is still enough insulin in the body, it is just not being used properly, leading to high blood sugar.


Metformin is used as first-line therapy for type 2 diabetes because it works to keep blood sugar levels controlled, and it is also safe and well-tolerated. While there is a list of side effects associated with the drug’s use, the most common tend to be gastrointestinal and include diarrhea and other stomach irritations.

While metformin is safe, some people may not be able to take it because of other medications they’re on, health problems such as liver or kidney disease, or if they consume incredibly high levels of alcohol regularly. Heavy alcohol consumption and metformin use can lead to a rare but life-threatening condition known as lactic acidosis.

In some cases, metformin is also prescribed alongside other diabetes drugs for the best results possible. These are referred to as combination drugs and make the condition much more manageable. There are different types of diabetes medications on the market. Still, they are typically used for people who can’t take metformin or have not seen any effective changes after taking the drug.

A Word From Verywell

Having type 2 diabetes isn't always easy. Still, metformin is a well-tolerated and effective drug on the market today that many people with the condition can use to help manage their disease effectively. Using metformin may come with side effects, but since the drug is so effective and reduces the risk of low blood sugar, it's the best option for those with type 2 diabetes.

Frequently Asked Questions

  • What do I do if metformin isn’t helping with my diabetes?

    If metformin isn’t helping your diabetes, you must speak to your healthcare provider. They will look into your dosage and other medication options to see which works best for you. There are also other options to combine different drugs with metformin for better results.

  • Do people with type 2 diabetes need insulin?

    No. People with type 2 diabetes rarely need insulin. That is because, in type 2 diabetes, the body still produces enough insulin. It just doesn’t use it properly. Insulin is necessary for people with type 1 diabetes because in this type the pancreas doesn’t produce enough insulin to handle blood sugar levels.

  • Does metformin cure diabetes?

    There is no cure for diabetes, including with the use of metformin. That said, the drug can effectively manage blood sugar levels long term for people with type 2 diabetes.

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023Diabetes Care. 2023;46(Suppl 1):S140-S157. doi:10.2337/dc23-S009

  2. Medline Plus. Metformin.

  3. Baker C, Retzik-Stahr C, Singh V, Plomondon R, Anderson V, Rasouli N. Should metformin remain the first-line therapy for treatment of type 2 diabetes? Ther Adv Endocrinol Metab. 2021 Jan 13;12:2042018820980225. doi:10.1177/2042018820980225

  4. UK National Health Service. Who can and cannot take Metformin.

  5. UK National Health Service. Taking Metformin with other medicines and herbal supplements.

  6. 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 Nov;98(46):e17918. doi:10.1097/MD.0000000000017918

  7. Beysel S, Unsal IO, Kizilgul M, Caliskan M, Ucan B, Cakal E. The effects of metformin in type 1 diabetes mellitus. BMC Endocr Disord. 2018 Jan 16;18(1):1. doi:10.1186/s12902-017-0228-9

  8. Aroda VR, Ratner RE. Metformin and type 2 diabetes prevention. Diabetes Spectr. 2018 Nov;31(4):336-342. doi:10.2337/ds18-0020

  9. Informed Health. Medication for type 2 diabetes.

  10. Meneghini LF. Insulin therapy for type 2 diabetes. Endocrine. 2013 Jun;43(3):529-34. doi:10.1007/s12020-012-9817-6

  11. University of California San Francisco. Type 2 diabetes FAQs.

By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.