What Are The Best Alternatives To Metformin (Dietitian’s Help)

best alternatives to metformin

Whether you are newly diagnosed with type 2 diabetes, or you have been dealing with it for years, you have likely been introduced to Metformin, or you know someone who is taking it. 

This large, white pill has a reputation for its unpleasant side effects, which will hopefully dissipate after a week or two. 

If your Metformin experience has left you feeling miserable, you may be wondering why it’s worth it to take the med. What are the best alternatives to Metformin?

In my article, I will discuss alternative drugs to Metformin and their side effects and contraindications. I will review Metformin, and discuss natural products or supplements that claim to have glucose-lowering properties.

Metformin has been used in the United States since 1995. It is effective and inexpensive, making it a popular drug. Read the article I wrote what is Meformin, for more of an in depth look.

Unfortunately, Metformin has some undesirable side effects which leave some people searching for another option. If you have not done so I have an informative article

Current Best Alternative Medications To Metformin 2021

Listed below, in order, are the six major agents following Metformin in the most current AACE/ACE (American Association of Clinical Endocrinology/American College of Endocrinology) guidelines.

GLP-1 RA (Glucagon-like peptide receptor agonist) 

  • GLP-1 medications are a daily injection.
  • GLP-1 is a hormone that regulates digestion and appetite 

Examples of GLP-1’s

  • Byetta (Exenatide), Victoza (Liraglutide), Trulicity (Dulaglutide), Ozempic (Semaglutide), Lyxumia (Licisenatide)

Benefits of GLP-1

  • Decreases output of glucose made by the liver
  • Stimulates the pancreas to release more insulin
  • Regulates gastric emptying
  • Promotes a feeling of satiety in the central nervous system therefore reducing appetite
  • Favors weight loss
  • Minimizes hypoglycemia (low blood sugar) unless it is combined with another glucose lowering agent
  • Like Metformin, it works on the overnight regulation for fasting blood sugar (GLP-1 medications and Metformin are the only diabetes medications that have this property)
  • CVD (cardiovascular disease) benefits
  • Preferred if ASCVD (Atherosclerotic cardiovascular disease) is present

Side Effects of GLP-1

SGLT2 (sodium-glucose cotransporter 2 inhibitors)

These medications are taken orally.

These drugs are preferred if there is evidence of decreased heart function or if CKD (chronic kidney disease) progression is present.

Examples of SGLT2 Inhibitors

  • Invokana (Canagliflozin), Jardiance (Empagliflozin), Farxiga (Dapagliflozin)

Benefits of SGLT2 Inhibitors

  • Increases the elimination of sugar in the urine
  • Prevents the reuptake of glucose into the bloodstream

Side Effects of SGLT2 Inhibitors

  • Risk of UTI (urinary tract infection)
  • Risk of hypoglycemia
  • Increased urination
  • Necrotizing fasciitis or Fourniers gangrene. This is a bacterial infection, a flesh-eating disease. It results in the death of soft tissue in the groin or perineum area. The symptoms include reddened or purple skin, severe pain, fever, and potential vomiting. 

DPP-4 (dipeptidyl peptidase-4 inhibitor)

  • These medications are taken orally
  • Can be used as a secondary treatment in addition to, or instead of, Metformin 
  • Can be used as monotherapy if intolerant or have contraindications to Metformin. 

Examples of DPP-4 Inhibitors

  • Sitagliptin (Januvia, Trajenta)
  • Saxagliptin (Onglyza)

Benefits of DPP-4 Inhibitors

  • Increase insulin release when blood sugars are high
  • Reduce glucose produced by the liver after meals   
  • Do NOT cause hypoglycemia or weight gain 
  • A1c reduction of 0.4 – 1%

Side Effects of DPP-4 Inhibitors

  • May cause stuffy/runny nose, sore throat, nausea, stomach pain, severe joint pain, and upper lung infections 
  • Risk of heart failure

TZD (thiazolidinediones) or glitazones

TZD medications are taken orally, as a pill.

Examples of TZD Medications

  • Actos (Pioglitizone),  Avandia (Rosiglitizone)
  • These meds do not increase insulin secretion

Benefits of TZD Medications

  • Increases sensitivity in muscle tissue
  • Inhibits hepatic gluconeogenesis (inhibits the liver from producing glucose, or sugar.)
  • A1c reduction of 1.5%
  • HDL (“good”)  cholesterol increase of up to 19%
  • May be able to reduce insulin dose if you are on insulin, but be aware of weight gain as a side effect
  • You may take this medication with or without food

Side Effects of TZD Medications

  • Weight gain, edema (fluid buildup), headache, exacerbate or cause heart failure, muscle pain, sore throat, increased risk of bone fracture
  • Avoid this medication with class three and four heart failure

AGI (Alpha-glucosidase inhibitors)

  • This medication is a pill that is taken with the first bite of each meal, 3 times daily
  • These medications slow the digestion of carbs, and delay the rate in which your body absorbs glucose
  • Can be used as monotherapy, or in addition to other glucose lowering agents

Examples of AGI’s

  • Acarbose (Precose), miglitol (Glyset)

Benefits of AGI’s

  • Lowers A1c by 0.5 – 0.8%
  • Reduces postprandial (post meal) glucose results
  • Raise post meal levels of GLP-1, which is a hormone that helps delay digestion, decrease appetite, and regulate blood sugars

Side effects of AGI’s

  • Stomach upset
  • Flatulence
  • Diarrhea

SU (sulfonylureas) 

Sulfonylureas come in pill form.

Examples of sulfonylureas

  • Glimepiride or Amaryl, glipizide or Glucotrol , glyburide or Micronase or DiaBeta

Benefits of sulfonylureas

  • Stimulates beta cells in the pancreas to release insulin
  • Improve insulin sensitivity
  • Suppress excess hepatic glucose production
  • A-1c reduction of 1.5 to 2% but less effective your blood sugars are greater than 250
  • Can be used as monotherapy or combination therapy

Side effects and contraindications

  • Weight gain, 5 to 10 pounds (2.3 – 4.5 kg)
  • Hypoglycemia
  • Headaches
  • Dizziness
  • Nausea
  • Rash
  • Nervousness
  • Increased sensitivity to the sun
  • Increased appetite
  • Caution with renal failure

Never stop any of your medications, including Metformin, without discussing it with your endocrinologist or primary care provider.

Natural or Organic Supplement Options to Metformin 

Note that natural products and supplements do not necessarily replace Metformin, but they may help you reduce your dose of other diabetes prescriptions, including insulin.

I do not promote, condone, or reject the use of natural substances or supplements. It is important that they do not interfere with your other medications, and that your diabetes team supports your decision.

Pre-diabetes is reversible. If you have prediabetes, these supplements may benefit your glycemic status. Combined with regular physical activity, practicing a healthful lifestyle, and maintaining appropriate weight, you are able to reverse your pre-diabetes. 

If you start taking any over the counter natural products or supplements, make sure to discuss this with your doctor and pharmacist to make sure they are safe, and that they will not interfere with any of your prescription medications.   

Supplements and herbal products are not regulated by the US FDA (Food and Drug Association) if these products are portrayed as a drug. For this reason, I advise caution because we cannot be absolutely sure of the ingredients. 

The US FDA does regulate supplements and herbal products if they are promoted as a food. (Source FDA Dietary Supplements)

Prescription medications work best when you are practicing a healthful lifestyle. The same is true for natural, organic products and supplements. 

Eat a balanced diet, see my article on the plate method for diet,  include daily, physical activity into your lifestyle, and eliminate tobacco, nicotine, alcohol, and drugs. Maintain a healthful weight. 

Examples of Organic Supplement Options to Metformin


This natural extract is derived from various plants. It serves as an anti-inflammatory, antioxidant, and antimicrobial. 

Berberine helps to reduce blood sugar levels and to regenerate the cells responsible for the production of insulin. It can also help improve cardiovascular health.

When I worked with the Native American community, berberine was recommended for some patients by Dr. Lorraine Turner at the CAIR Clinic (Center for American Indian Resources) in Duluth Minnesota.

In clinical studies, berberine has been found to be as effective as Metformin.


One of our patients is in her early 60’s. She was delighted when we were able to decrease her insulin.

The following mentions have NOT been clinically proven to lower blood glucose. Further studies are needed.

Bitter Melon Extract

Claims to reduce fat in the body. It prevents inflammation and suppresses the elevation of glucose in the blood. It has anticancer properties and antioxidants, and may help with weight loss.


Ginseng has properties that help regulate the level of glucose in the blood. Reports of increased energy and decreased stress levels.

Aloe vera

This plant has properties that regulate blood sugar levels naturally. Aloe vera helps improve the functioning of the kidneys and colon. Aloe vera is also anti-inflammatory and antioxidant. It stimulates the secretion of insulin. It has no known side effects.

Bilberry extract

Among its properties are the strengthening of blood vessels, helps regulate the digestive system, helps improve blood circulation, and helps regulate the level of sugar in the blood. Also, it helps prevent retinopathy, a common eye disease in diabetic people where. If not treated in time, it can cause permanent loss of sight.


Cinnamon helps reduce blood sugar levels and increases the body’s ability to produce insulin. It has many antioxidants, and it aids digestion, which reduces the risk of sugar spikes after a meal.

The following is a “recipe” that was created by the late biochemist, Ralph Anderson, Ph.D.

My husband had prediabetes back in 2009. This was suggested by a biochemist to help prevent type 2 diabetes:

Take with food:

2 Tbsp cold pressed Extra Virgin Olive Oil

3 capsules Cinnamon 

1 capsule Cayenne Pepper (Cool Cayenne 40,000 or 100,000 HU)

2 capsule s Chromium

2 capsules Vanadium

My husband took this combination for approximately one year. He reported a slight drop in A1c and improved blood sugars. His A1c had gone from 5.9% to 5.5%. (Prediabetes is an A1c of 5,7 – 6.4%.) His average blood sugar was 108 mg/dL after taking this combination.

By no means, am I promoting the aforementioned, rather, I am identifying alternative options. I recommend consulting your physician before adding something new.

Additional Metformin Alternative Advice

You will find outdated advice on the internet when searching for alternatives to Metformin, including a drug called, Prandin.

Is Prandin An Old Drug?

Prandin (Repaglinide) is in the glinide category of diabetes medications. It was introduced as an oral medication in the United States in 1983.

Prandin causes weight gain, stomach upset, and hypoglycemia. It is not in the ADA algorithm. In my 20+ years of practice, I personally have never seen anyone with a prescription for Prandin.


Metformin is an oral drug that helps people manage type 2 diabetes and helps prevent type 2 in those with prediabetes. 

This prescription has many side effects that can be unpleasant for people. According to a study mentioned in ScienceDaily, 30% of Metformin prescriptions are not taken at all due to side effects. 

I have outlined preferred alternative prescription drugs, and have highlighted some popular natural supplements without clinical evidence. Double check to make sure you are taking your Metformin correctly before making your decision.

Always be sure to discuss any of your plans or thoughts with your primary provider before making any adjustment to your diabetes health care plan.  

Medications work best when accompanied by a healthful lifestyle. Follow your meal plan, obtain regular physical activity, limit alcohol use, and quit smoking. 

Schedule an appointment with your doctor and/or diabetes care and education specialist if you are considering a change.







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