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Biguanides
`
`Biguanides (better known as metformin) are a type of oral diabetes
`medication that helps lower blood sugar levels for people with Type 2
`diabetes. Healthcare providers prescribe this medication for other
`conditions, as well, like PCOS and gestational diabetes.
`
`Contents
`
`Overview
`
`Procedure Details
`
`Risks / Benets
`
`When to Call the Doctor
`
`Overview
`
`What are biguanides?
`
`Biguanides are a type of oral diabetes medication. They help manage
`diabetes — mainly Type 2 diabetes — by lowering blood glucose (sugar)
`levels.
`
`Healthcare providers prescribe them for other conditions, as well.
`
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`
`Is metformin the only biguanide?
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00001
`
`

`

`Yes, metformin is the only biguanide available in most countries. Its brand
`names include:
`
`Glucophage®.
`
`Glucophage XR®.
`
`Glumetza®.
`
`Fortamet®.
`
`Riomet®.
`
`ADVERTISEMENT
`
`Cleveland Clinic is a non-prot academic medical
`center. Advertising on our site helps support our
`mission. We do not endorse non-Cleveland Clinic
`products or services. Policy
`
`What conditions do biguanides treat or
`manage?
`
`The U.S. Food and Drug Administration (FDA) approved metformin (the only
`biguanide) in 1994 for the management of Type 2 diabetes (T2D). Since
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00002
`
`

`

`then, metformin has become the most widely prescribed oral diabetes
`medication and rst-line therapy for T2D.
`
`Healthcare providers sometimes prescribe biguanides for other conditions.
`This is an off-label, or non-FDA-approved, use of the medication. Non-FDA-
`approved uses of metformin include:
`
`Management of gestational diabetes.
`
`Management of prediabetes.
`
`Management of Type 1 diabetes.
`
`Management of antipsychotic medication-induced weight gain.
`
`Treatment and prevention of polycystic ovary syndrome (PCOS).
`
`Researchers are also studying biguanides for their anticancer effects.
`Studies show that people taking metformin for diabetes have a signicant
`reduction in their risk of cancer.
`
`How common are biguanides?
`
`Biguanides (metformin) are a very common medication. In 2020, there were
`approximately 92 million prescriptions for metformin in the U.S.
`
`Procedure Details
`
`How do biguanides work?
`
`Biguanides lower blood glucose (sugar) levels by decreasing the amount of
`glucose your liver produces and releases into your bloodstream. They also
`help lower blood glucose levels by making your skeletal muscle tissue more
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00003
`
`

`

`sensitive to insulin so it can absorb glucose for energy. This increases
`insulin sensitivity and reduces insulin resistance. These bodily changes
`help manage diabetes.
`
`In PCOS, biguanides decreases insulin levels, which then decrease
`luteinizing hormone and androgen levels. This helps regulate your
`menstrual cycle (period).
`
`ADVERTISEMENT
`
`How long will I need to take biguanides?
`
`Diabetes is typically a chronic condition (except for gestational diabetes),
`so you’ll likely take metformin long-term. It’s important to remember that
`diabetes management involves several strategies, including regular
`exercise and meal planning. While metformin is effective, it alone can’t treat
`diabetes.
`
`Your healthcare provider will be able to give you more information about
`how long you’ll take metformin and other strategies to best manage
`diabetes.
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00004
`
`

`

`Care at Cleveland Clinic
`
`Adult Type 2 Diabetes Management
`
`Pediatric Type 2 Diabetes Management
`
`Find a Doctor and Specialists
`
`Find a Pediatric Doctor and Specialists
`
`Make an Appointment
`
`Risks / Benets
`
`What are the potential benets of
`biguanides?
`
`Biguanides are effective. For people with Type 2 diabetes, biguanides
`(metformin) can decrease their A1C levels by about 1%.
`
`Studies show that biguanides are also effective in preventing or delaying
`the development of Type 2 diabetes in people at high risk. A study
`demonstrated that intensive lifestyle intervention and metformin therapy
`reduced progression from prediabetes to diabetes by 58% and 31%,
`respectively.
`
`Studies also show that metformin may decrease your risk for
`cardiovascular disease.
`
`ADVERTISEMENT
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00005
`
`

`

`What are the side effects of biguanides?
`
`Common side effects of biguanides (metformin) include diarrhea and
`nausea and vomiting. They affect up to 30% of people taking the
`medication.
`
`Less common side effects include:
`
`Chest discomfort.
`
`Headache.
`
`Excessive sweating (diaphoresis).
`
`Low blood sugar (hypoglycemia).
`
`Weakness.
`
`What are the risks or complications of
`biguanides?
`
`Biguanides (metformin) are generally safe, but taking them may result in
`certain complications, including:
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00006
`
`

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`Vitamin B12 deciency.
`
`Lactic acidosis.
`
`Drug interactions.
`
`Vitamin B12 deciency
`
`Long-term use of metformin may cause your vitamin B12 levels to
`decrease. Your healthcare provider will likely monitor your levels while you
`take the medication, especially if you have anemia or peripheral neuropathy.
`Your provider may recommend a vitamin B12 supplement.
`
`Lactic acidosis
`
`Metformin has a black box warning for lactic acidosis. This is a rare,
`potentially life-threatening complication. It affects every 1 in 30,000 people
`taking metformin. Your provider will be monitoring your kidney function
`levels while you take the medication. They’ll tell you to stop taking it if
`there’s any noted change in your kidney function.
`
`Lactic acidosis happens when lactic acid builds up in your body, which
`leads to metabolic acidosis. Risk factors for lactic acidosis include:
`
`Liver disease or kidney disease.
`
`Being over the age of 65.
`
`Recently having had surgery.
`
`Low oxygen levels (hypoxia).
`
`Alcohol use disorder.
`
`Symptoms of lactic acidosis and metabolic acidosis include:
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00007
`
`

`

`Fatigue.
`
`Weakness.
`
`Nausea and vomiting.
`
`Abdominal pain.
`
`Rapid breathing or long, deep breathing.
`
`If you have these symptoms, call 911 (or your local emergency services
`number) or go to the nearest emergency department as soon as possible.
`
`While this complication is rare, if lactic acidosis isn’t treated in time, it can
`lead to death.
`
`Drug interactions
`
`Taking metformin with other medications can lead to complications. Before
`starting any new medication, make sure you tell your healthcare provider
`about all the medications you take, including prescriptions, over-the-counter
`(OTC) drugs and supplements.
`
`Taking certain medications while also taking biguanides may increase your
`risk of developing lactic acidosis. They include (but aren’t limited to):
`
`Bupropion.
`
`Carbonic anhydrase inhibitors.
`
`Cephalexin.
`
`Cimetidine.
`
`Dolutegravir.
`
`Glycopyrrolate.
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00008
`
`

`

`Lamotrigine.
`
`Ranolazine.
`
`Topiramate.
`
`Taking certain medications in addition to biguanides can increase your risk
`of experiencing low blood sugar (hypoglycemia). They include:
`
`Androgens.
`
`Alpha-lipoic acid.
`
`Salicylates.
`
`Selective serotonin reuptake inhibitors (SSRIs).
`
`Quinolones.
`
`Prothionamide.
`
`Pegvisomant.
`
`When to Call the Doctor
`
`When should I call my healthcare provider?
`
`You should have regular appointments with your healthcare provider when
`you’re taking a biguanide to assess how well it’s working.
`
`Otherwise, talk to your healthcare provider in the following situations:
`
`If you develop bothersome side effects.
`
`If it’s not working to manage your condition (like diabetes or PCOS).
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00009
`
`

`

`If you’re thinking of stopping the medication.
`
`A note from Cleveland Clinic
`
`Biguanides (metformin) are a well-studied class of oral diabetes
`medication. They’re proven to be generally safe and effective at managing
`Type 2 diabetes and other conditions. If you have any questions about
`taking metformin, don’t hesitate to ask your healthcare provider. They’re
`available to help you.
`
`Medically Reviewed
`Last reviewed by a Cleveland Clinic medical professional on 05/22/2023.
`Learn more about our editorial process.
`
`References
`
`Appointments 216.444.6568
`
`APPOINTMENTS & LOCATIONS
`
`REQUEST AN APPOINTMENT
`
`VIRTUAL VISITS FOR DIABETES
`
`Ad
`
`Novo Nordisk Exhibit 2366
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00010
`
`

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