Biguanides (Metformin): Uses, How They Work, Side Effects and Risks
Updated: 6 days ago
Written and medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026 · How we review
Quick Answer: What are biguanides?
Biguanides are oral diabetes medicines that lower blood sugar, mainly in type 2 diabetes, and metformin is the only one available in most countries. Metformin makes the liver release less sugar and helps muscles respond to insulin, lowering A1C by about 1%. Stomach upset is common; rare lactic acidosis needs emergency care. [6]
What the research says
Metformin cut the risk of developing type 2 diabetes by nearly a third. In a trial of 3,234 adults with high blood sugar, metformin lowered new diabetes cases by 31% over about 2.8 years compared with placebo. Lifestyle changes lowered it by 58%, so both work and lifestyle works best. (Knowler et al., N Engl J Med, 2002)
In overweight people with type 2 diabetes, metformin lowered the risk of death. In a trial of 753 patients followed for a median of 10.7 years, those on metformin had 36% lower all-cause mortality and 42% fewer diabetes-related deaths than those on conventional treatment. (UKPDS Group, Lancet, 1998)
Long-term use can lower vitamin B12. In a long-term follow-up of more than 2,000 people, low or borderline-low B12 was found in 20.3% of metformin users vs 15.6% on placebo at 13 years. Each year of use raised the odds of deficiency by 13%. (Aroda et al., J Clin Endocrinol Metab, 2016)
What are biguanides?
Biguanides are a type of oral diabetes medication that you take by mouth.
They help manage diabetes, mainly type 2 diabetes, by lowering the amount of glucose (sugar) in your blood. [6]
Healthcare providers also prescribe them for some other conditions, which you'll find below.
Is metformin the only biguanide?
Metformin is the only biguanide available in most countries. You may see it sold under these brand names:
Glucophage®
Glucophage XR®
Glumetza®
Fortamet®
Riomet®
So when a doctor says "biguanide," they almost always mean metformin.
What do biguanides treat?
Biguanides treat type 2 diabetes, the use the U.S. Food and Drug Administration (FDA) approved metformin for in 1994, and providers also prescribe them off-label for several other conditions. [6]
Since then, it has become the most widely prescribed oral diabetes medicine. It is the usual first-line treatment for type 2 diabetes, meaning it's often the first medicine tried.
It is also very common. In 2020, there were about 92 million metformin prescriptions in the U.S. alone.
Providers sometimes prescribe it "off-label." That means for a use the FDA hasn't formally approved, based on medical evidence.
Use | FDA-approved? |
Type 2 diabetes | ✅ Yes |
Off-label | |
Off-label | |
Type 1 diabetes | Off-label |
Weight gain caused by antipsychotic medicines | Off-label |
Off-label (treatment and prevention) |
Researchers are also studying biguanides for possible anticancer effects. Some observational studies suggest people taking metformin for diabetes may have a lower risk of some cancers, but clinical trials have not proven this. This is an active area of research, not an approved use. [5]
How do biguanides work?
Biguanides lower blood sugar by reducing how much glucose your liver releases and by making your skeletal muscle more sensitive to insulin. [5]
1. Your liver. They reduce the amount of glucose your liver makes and releases into your bloodstream.
2. Your muscles. They make your skeletal muscle more sensitive to insulin. Insulin is the hormone that moves sugar from your blood into your cells. When muscle responds better, it absorbs more glucose for energy.
Together, these changes increase insulin sensitivity and reduce insulin resistance. That's what helps control diabetes.
In PCOS (PMOS), biguanides lower insulin levels. Lower insulin then lowers luteinizing hormone and androgen ("male-type" hormone) levels. This helps regulate your menstrual cycle.
How long will you need to take metformin?
Most people take metformin long-term because diabetes is usually a chronic condition, with gestational diabetes as the exception.
Keep in mind that metformin can't treat diabetes on its own. Managing diabetes involves several steps working together:
Regular exercise
Meal planning
Medication, such as metformin
Your healthcare provider will tell you how long you'll need metformin and which other strategies fit you best.
What are the benefits of biguanides?
Biguanides lower A1C by about 1% in type 2 diabetes, can prevent or delay diabetes in people at high risk, may lower cardiovascular risk and are well studied. [4]
Benefit | What it means for you |
Lowers A1C | In type 2 diabetes, metformin lowers A1C by about 1% |
Prevents or delays diabetes | In people at high risk, metformin cut progression from prediabetes to diabetes by 31%. Intensive lifestyle changes cut it by 58% |
May protect your heart | Studies suggest metformin may lower your risk of cardiovascular disease |
Well studied | Proven to be generally safe and effective |
A1C is a blood test that reflects your average blood sugar over time.
What are the side effects of biguanides?
The most common side effects of biguanides are diarrhea, nausea and vomiting, which affect up to 30% of people taking metformin. [6]
Diarrhea
Nausea
Vomiting
Less common side effects include:
Chest discomfort
Headache
Excessive sweating (diaphoresis)
Weakness
If side effects bother you, don't stop the medicine on your own. Talk to your provider first.
What are the risks and complications of biguanides?
Metformin is generally safe, but it can lead to three main complications, which are vitamin B12 deficiency, lactic acidosis and drug interactions. [6]
Vitamin B12 deficiency
Long-term metformin use can lower your vitamin B12 levels. [3]
Your provider will likely check your levels while you take it. This matters most if you have anemia (low red blood cells) or peripheral neuropathy (nerve damage, often felt as numbness or tingling in your hands and feet).
Your provider may recommend a vitamin B12 supplement. Learn more in our guide to vitamin B12 deficiency.
Lactic acidosis
Metformin carries a black box warning, the FDA's strongest safety warning, for lactic acidosis.
Lactic acidosis happens when lactic acid builds up in your body. This makes your blood too acidic (metabolic acidosis). It is rare, affecting about 1 in 30,000 people who take metformin. But it can be life-threatening if not treated in time. [6]
Your provider will monitor your kidney function while you take metformin. If your kidney function changes, they'll tell you to stop. Metformin should not be used when kidney function is severely reduced (eGFR below 30), and it may need to be paused before imaging tests that use iodine contrast dye or before some procedures. See how your kidneys filter your blood.
Risk factors for lactic acidosis
Liver disease or kidney disease
Being over age 65
Having had surgery recently
Low oxygen levels (hypoxia)
Alcohol use disorder
Symptoms of lactic acidosis
Fatigue
Weakness
Nausea and vomiting
Belly (abdominal) pain
Rapid breathing, or long, deep breaths
🚨 If you have these symptoms, call your local emergency number or go to the nearest emergency department right away.
Drug interactions
Some medicines can cause problems when taken with metformin. Before starting anything new, tell your provider about everything you take. That includes prescriptions, over-the-counter (OTC) drugs and supplements.
Interaction risk | Medicines (examples, not a complete list) |
Higher risk of lactic acidosis | Bupropion, carbonic anhydrase inhibitors, cephalexin, cimetidine, dolutegravir, glycopyrrolate, lamotrigine, ranolazine, topiramate |
Higher risk of low blood sugar | Androgens, alpha-lipoic acid, salicylates, SSRIs (a type of antidepressant), quinolone antibiotics, prothionamide, pegvisomant |
When should you call your healthcare provider about biguanides?
Contact your healthcare provider if side effects bother you, metformin isn't controlling your condition or you're thinking about stopping it, and go to the emergency department for signs of lactic acidosis.
You should have regular appointments while you take a biguanide. Your provider uses them to check how well it's working.
Also contact your provider if:
You develop side effects that bother you
It isn't controlling your condition, such as diabetes or PCOS
You're thinking about stopping the medicine
Go to the emergency department if you have signs of lactic acidosis, listed above.
Conclusion
Biguanides, better known as metformin, are a well-studied, generally safe and effective diabetes medicine. They lower blood sugar by calming your liver's sugar output and helping your muscles use insulin.
They're the usual first choice for type 2 diabetes. Providers also use them for prediabetes, PCOS and gestational diabetes.
Most side effects are mild and digestive. The key safety steps are simple: get your kidney function and B12 checked, share your full medicine list, and know the warning signs of lactic acidosis.
Your next step: Save or print this guide and bring it to your next appointment. Ask your provider: "Is metformin still the right fit for me, and when should my kidney function and B12 be checked?" Exploring other options? Read our guide to SGLT2 inhibitors, another class of type 2 diabetes medicine.
Frequently asked questions
What is a biguanide?
A biguanide is a type of oral diabetes medicine that lowers blood sugar. It reduces how much sugar your liver releases and helps your muscles respond to insulin.
Is metformin the same as a biguanide?
Yes, in practice. Metformin is the only biguanide available in most countries, so the two terms are often used interchangeably.
What is metformin used for besides diabetes?
Off-label uses include prediabetes, gestational diabetes, PCOS (PMOS), type 1 diabetes and weight gain caused by antipsychotic medicines.
How much does metformin lower A1C?
In people with type 2 diabetes, metformin lowers A1C by about 1% on average.
What are the most common side effects of metformin?
Diarrhea, nausea and vomiting. They affect up to 30% of people taking it.
Does metformin cause low blood sugar?
It's a less common side effect. The risk rises when metformin is combined with certain medicines, such as SSRIs, salicylates or quinolone antibiotics.
Does metformin cause vitamin B12 deficiency?
Long-term use can lower B12 levels. Your provider may test your levels and recommend a supplement, especially if you have anemia or nerve damage.
How rare is lactic acidosis with metformin?
It affects about 1 in 30,000 people taking metformin. It is rare but can be life-threatening, so know its symptoms.
Can metformin cure diabetes?
No. Metformin helps manage diabetes, but it works best with regular exercise and meal planning.
Can I stop taking metformin on my own?
Talk to your healthcare provider before stopping. They can adjust your treatment safely.
Related Reading
Diabetes Medications: Types, How They Work, and Side Effects — Complete Guide compares the main diabetes medicines and how they work.
A1C Test: Normal Levels, Prediabetes and Diabetes Ranges and What Affects Results explains what the A1C test measures and what results mean.
Understanding Vitamin B12 Deficiency: Causes, Symptoms, and Recovery covers vitamin B12 deficiency symptoms, causes and treatment.
Prediabetes: Symptoms, Causes, and Treatment explains prediabetes and steps to prevent type 2 diabetes.
References
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. PMID: 11832527. doi:10.1056/NEJMoa012512
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-865. PMID: 9742977. https://doi.org/10.1016/S0140-6736(98)07037-8
Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761. PMID: 26900641. doi:10.1210/jc.2015-3754
Aroda VR, Ratner RE. Metformin and type 2 diabetes prevention. Diabetes Spectr. 2018;31(4):336-342. PMID: 30510389. doi:10.2337/ds18-0020
Di Magno L, Di Pastena F, Bordone R, et al. The mechanism of action of biguanides: new answers to a complex question. Cancers (Basel). 2022;14(13):3220. PMID: 35804992. doi:10.3390/cancers14133220
Corcoran C, Jacobs TF. Metformin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; updated August 17, 2023. https://www.ncbi.nlm.nih.gov/books/NBK518983/
Cleveland Clinic. Biguanides: What They Are, Uses & Side Effects. Cleveland Clinic. Last updated May 22, 2023. https://my.clevelandclinic.org/health/treatments/25004-biguanides
Medical disclaimer
This article is for general education and does not replace advice from your own healthcare provider.
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