In summary

Does CBD Interact With Metformin? Is It Safe to Take With Metformin and Other Antihyperglycemic Agents?

  • Metformin is a U.S. Food and Drug Administration (FDA) approved medicine that is considered the first-line treatment for type 2 diabetes. Doctors prescribe the drug as monotherapy or together with other medications to manage high blood sugar levels in the body (1)
  • Using metformin has proven to be an effective solution in preventing diabetes in high-risk individuals. Some adverse reactions to the drug may be possible but are often trivial compared to the benefits that it offers (2)
  • Cannabidiol (CBD), the non-psychoactive phytocannabinoid present in Cannabis sativa, is said to have therapeutic benefits, especially for people with diabetes. Several clinical trials on mice and rats show positive improvements in the test subjects’ incidence of diabetes while reducing overall fat accumulation and high blood pressure related to the condition (3-4)
  • Since metformin is capable of effectively treating type 2 diabetes, it may be used together with CBD to improve the quality of life for people with the condition. However, no research exists to prove that these products are safe for use with each other.
  • The antihyperglycemic agent insulin may work well when used together with CBD oil. Research in 2016 on type 2 diabetes patients shows that a combination of tetrahydrocannabinol (THC) and CBD can lower insulin resistance while improving the effects of insulin in the body (5)
The full article

Best CBD Oils for Managing Diabetes

Editor's Pick

Spruce 750mg Lab Grade CBD Oil

Specifically formulated to be more palatable to CBD users
Spruce 750mg Lab Grade CBD Oil Bottle
  • Overall Clinical Score
    99%
    Editor's Pick
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...New CBD users
  • Summary

    Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.

    Pro's
    Cons's
     Mid-strength  No other flavors
     Natural peppermint flavor
     Made from 100% organic and natural ingredients
  • Features
    Discount pricing available? 20% Off Coupon Code: CBDCLINICALS
    Source
    Source of Hemp
    Kentucky, USA & North Carolina, USA
    Form Oil Tincture
    Ingredients Organic Hemp Seed Oil, Full Spectrum CBD Oil
    Type
    Type of CBD
    Full Spectrum
    Extraction
    Extraction Method
    Moonshine extraction method
    How to take it Under tongue
    Potency
    Potency - CBD Per Bottle
    750 mg per bottle
    Carrier Oil Organic Hemp Seed Oil
    Concentration
    CBD Concentration Per Serving
    25mg of CBD per dropper full (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
    Flavours Peppermint
    Price Range $89 ($75.65 for subscriptions, 15% discount from regular price)
    $/mg CBD
    Price ($/mg)
    $0.12/mg ($0.10/mg with subscription)
    Shipping
    Shipping/Time to delivery
    2-4 business days (first class USPS)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants Organic, Non-GMO, no pesticides, no herbicides, no solvents or chemical fertilizers, No preservatives or sweeteners
    Allergens Vegan, Gluten free
    Refund policy Within 30 days
    Recommended for New CBD users
    Countries served USA only (all 50 states)
Check Latest Prices
Best Organic

NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil

Perfect for anyone who are looking for CBD products that promote a healthy body and mind.
NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil
  • Overall Clinical Score
    99%
    Best Organic
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Health-conscious persons
  • Summary

    Natural remedy for various illnesses. NuLeaf Naturals’ CBD oil is a whole-plant extract containing a full spectrum of naturally occurring synergistic cannabinoids and terpenes.

    Pro's
    Cons's
     Pure CBD hemp  No other flavors
     All natural
     Approximately 300 drops total
  • Features
    Discount pricing available? 20% Off Coupon Code: CBDCLINICALS20
    Source
    Source of Hemp
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    Form Oil Tincture
    Ingredients Full Spectrum Hemp Extract, Organic Virgin Hemp Seed Oil
    Type
    Type of CBD
    Full Spectrum CBD
    Extraction
    Extraction Method
    CO2 Method
    How to take it Under the tongue for approximately 30 seconds before swallowing
    Potency
    Potency - CBD Per Bottle
    900mg per bottle
    Carrier Oil Organic Hemp Oil
    Concentration
    CBD Concentration Per Serving
    60mg per dropper full (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
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    Price Range $99 - $434
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    Price ($/mg)
    $0.08 - $0.13
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    Shipping/Time to delivery
    2-3 Days via USPS
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants No additives or preservatives, Non-GMO, NO herbicides, pesticides, or chemical fertilizers
    Allergens Not specified
    Refund policy Within 30 days
    Recommended for Health-conscious persons
    Countries served USA (all 50 states) and over 40 countries including Australia, Azerbaijan, Beliza, Bosnia & Herzegovina, Brazil, Chile, China, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Ireland, Israel, Japan, Latvia, Lebanon, Lithuania, Macao, Malaysia, Malta, Netherlands, New Zealand, Oman, Paraguay, Poland, Portugal, Saudi Arabia, Serbia, Singapore, South Korea, Sweden, Switzerland, United Arab Emirates, United Kingdom, Uruguay, and many more.
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4x the strength of a regular cbd oil
Sabaidee Super Good Vibes CBD Oil
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  • Clinical Scores
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    Customer Service
    Lab Testing Transparency
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    Perfect for...Patients who are looking for serious CBD oil support
  • Summary

    Super Good Vibes CBD Oil provides the purest and highest quality Cannabidiol (CBD) on the market as well as other high quality phytocannabinoids, terpenes, vitamins, omega fatty acids, trace minerals, and other beneficial for your health elements, which all work together to provide benefits.

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     Extra strong  No other flavors
     Significant benefits with just a few drops
     100% Natural ingredients
  • Features
    Discount pricing available? 15% Off Coupon Code: CBDCLINICALS15
    Source
    Source of Hemp
    Colorado, USA
    Form Oil Tincture
    Ingredients Cannabidiol (CBD), Coconut Medium-chain triglycerides (MCT) Oil, Peppermint oil
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2-extraction
    How to take it Using 1-3 servings per day as needed is a good start to determine how much you need
    Potency
    Potency - CBD Per Bottle
    1000 mg per bottle
    Carrier Oil Coconut MCT Oil
    Concentration
    CBD Concentration Per Serving
    33.5 mg per dropper (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
    Flavours Peppermint
    Price Range Single Bottle - $119.95, 2-Pack - $109.97 each, 3-Pack - $98.31 each, 6-Pack - $79.99 each
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    Single bottle - $0.010, 2-Pack - $0.011, 3-Pack - $0.009, 6-Pack - $0.007
    Shipping
    Shipping/Time to delivery
    3-5 Business days
    Lab Tests
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    Third Party Lab Tested post formulation for safety and potency, available on website
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    Allergens Vegan and Gluten-free
    Refund policy Within 30 days
    Recommended for Patients who are looking for serious CBD oil support
    Countries served USA only (all 50 states)
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Best Natural Alternative

cbdMD CBD Oil Tincture Natural 1500mg

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  • Overall Clinical Score
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    Best Natural Alternative
  • Clinical Scores
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    Lab Testing Transparency
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    Perfect for...Daily CBD oil users
  • Summary

    cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.

    Pro's
    Cons's
     Various delicious flavors to choose from  cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options
     Has vegan, organic, and gluten-free ingredients
     Free shipping for this particular product within USA
     World-class customer service team
  • Features
    Discount pricing available? 15% Off Coupon Code: cbdMD15
    Source
    Source of Hemp
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    Form Oil Tincture
    Ingredients Cannabidiol (CBD), MCT Oil, and Flavoring
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2 extraction method
    How to take it Under tongue
    Potency
    Potency - CBD Per Bottle
    1500mg per bottle
    Carrier Oil Organic Coconut MCT Oil
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    CBD Concentration Per Serving
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    Third Party Lab Tested post formulation for safety and potency, available on website
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    Refund policy Within 30 days
    Recommended for Daily CBD oil users
    Countries served USA only (all 50 states)
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Can CBD Be Taken with Metformin?

Metformin is a U.S. Food and Drug Administration (FDA) approved medicine commonly used to treat type 2 diabetes. Doctors often prescribe this drug on its own or in combination with other diabetes medications to manage high glucose levels (6)

The medication has proven to be effective in preventing diabetes in high-risk individuals while also lowering the majority of its complications. Although there are some adverse reactions to metformin use, reports state that these effects are trivial when considering the benefits (7)

Cannabidiol (CBD), on the other hand, is a phytocannabinoid present in the Cannabis sativa plant. It is the non-euphoric component in cannabis that is said to contain therapeutic properties.

A study in 2016 on diabetic mice reveals that CBD treatment is capable of lowering the incidence of diabetes in the subjects. The mice were given a daily dose of 5 mg/kg CBD at least five times a week for ten weeks (8)

Additional research in 2018 investigates the mechanism of action of phytocannabinoids as anti-diabetic and anti-obesity agents. The study shows that cannabinoids can potentially support the treatment of insulin resistance caused by diabetes and obesity (9)

Seeing as metformin can effectively treat diabetes while CBD has possible healing properties, it is only natural to think of combining the two of them. However, there is no study proving that these products are compatible with each other.

There are enzymes in the liver that metabolize the number of active ingredients in medications taken by an individual. These are also the same proteins that the body uses to break down CBD.

In past research, CBD is seen as a potent inhibitor of cytochrome P450 enzymes. As an inhibitor, this means that taking it along with other medications may hinder liver enzymes from correctly processing other drugs (10-11)

Such a scenario could lead to an increased intake of active ingredients in medicine, causing problems related to toxicity.

CBD interaction with CYP450 is because of how it affects the endocannabinoid system (ECS). The ECS is a complex system found in humans and animals that regulates the central nervous system, among others (12).

Metformin use comes with its side effects, and the more this medication enters the bloodstream, the higher the possibility of harmful reactions. Although its effects are not significant, it may cause a condition known as lactic acidosis. This condition brings with it symptoms such as muscle pain, drowsiness, dizziness, chills, and difficulty in breathing (13).

Since there is no clear indication of whether metformin users are at risk or not, if they use CBD, it is always better to err on the side of caution. People using metformin for diabetes should consult a doctor knowledgeable in cannabis before applying CBD in their regimen.

Only these professionals can provide a concept of the right dosage of these two products to avoid any adverse side effects.

Can Another Antihyperglycemic Be a Substitute for Metformin So CBD Oil Can Be Taken?

Insulin is an antihyperglycemic agent that is used to lower high blood sugar in people who have diabetes. Doctors often apply it by subcutaneous injection, but there are other forms that they can inject intravenously.

Research in 2016 on 62 subjects with type 2 diabetes reveals that a combination of tetrahydrocannabinol (THC) and CBD can decrease insulin resistance while stimulating the effect of insulin in the body. These same subjects were non-insulin-treated and were able to tolerate both CBD and THC well (14).

Another study in 2018 shows that low dosage CBD increases glucose uptake, lowers fat accumulation, and reverses insulin resistance in rats (15). This may be an additional indication that CBD can be used together with insulin to improve its effectiveness.

Although CBD and insulin intake in rodents may not be the same in humans, there is still a possibility that cannabidiol can enhance insulin efficacy. This is especially true since animal models are often used to understand how drugs work in human beings (16).

More research is needed to understand further the effectiveness and safety of using these two to treat diabetes.

Can CBD Replace Metformin?

As of this time, no research proves CBD to be a safe alternative to metformin use in humans who have diabetes. The majority of studies on how CBD can affect diabetes were carried out on rats and mice.

A study as early as 2006 on non-obese diabetic mice shows that CBD is capable of lowering the incidence of possible diabetes by changing the immune response system in rodents. The non-treated mice had a probability of 86% to develop diabetes, while CBD-treated subjects only had 30% (17).

The CBD treatment also significantly reduced plasma blood levels of the pro-inflammatory cytokines, while also lowering the possibility of pancreatic disease.

In 2016, research showed that cannabidiol could delay the onset of type 1 diabetes while remarkably reducing inflammation in the pancreas caused by the said condition. Female non-obese diabetic mice were administered daily intake of CBD for several weeks (18).

Another study in 2019 carried out on middle-aged diabetic rats wanted to test the beneficial effects of CBD on both ischemic diseases and diabetes. It revealed that CBD has effects on neuropathic pain, can improve memory performance, and lowers hippocampal levels of inflammation markers (19)

Experts suggest that perhaps medical marijuana and cannabinoids like CBD gummies can be used to treat the symptoms of diabetes. Since the studies on CBD as an antihyperglycemic are limited, it is always best to seek advice from a medical expert before considering replacing current anti-diabetic medication.

Drugs That Can Interact with Metformin

Metformin contains positively charged molecules (cationic) that can compete with similarly charged drugs for renal secretion via organic cation transporters found in the kidneys.

Quinidine, procainamide, trimethoprim, digoxin, and vancomycin are cationic medications that can interact with metformin. However, only cimetidine, which can be bought over-the-counter for heartburn, is linked to a case of metformin-associated lactic acidosis (MALA) (20).

The following are other medications that can have drug interactions with metformin:

  • Diuretics
  • Corticosteroids
  • Thyroid medications
  • Estrogen and oral contraceptives
  • Phenytoin
  • Calcium channel blockers

Mixing the drugs listed above, together with metformin, may affect blood sugar control in the body. Patients need to monitor their blood sugar levels frequently and notify their doctors of any sudden changes.

These drugs can reduce the ability of the kidneys to eliminate metformin from the blood and thus lead to lactic acidosis:

  • Cimetidine
  • Ranolazine
  • Vandetanib
  • Dolutegravir

Individuals should consult a doctor to see if these drug combinations are worth the risk. There may be safer options available that do not have the same probability of danger.

Below are medications that may increase the risk of lactic acidosis on metformin users:

  • Carbonic anhydrase inhibitors (CAIs) such as acetazolamide or topiramate

Regular monitoring of patients taking CAIs together with metformin may be necessary as this can aid in detecting early signs of lactic acidosis.

It is always best to consult a doctor to be aware of the possible side effects of metformin use. Physicians can change the dosage or even suggest a safer, alternate medication.

People switching from immediate-release to extended-release metformin tablets may experience fewer instances of diarrhea, as suggested by a study in 2004 (21).

Doctors continually monitor for signs of anemia and vitamin B-12 deficiency in individuals that have been taking metformin for at least a few months. Consuming iron and vitamin B-12 supplements may help prevent these issues if they arise in long-term metformin users.

Best CBD Oils for Managing Diabetes

Editor's Pick

Spruce 750mg Lab Grade CBD Oil

Specifically formulated to be more palatable to CBD users
Spruce 750mg Lab Grade CBD Oil Bottle
  • Overall Clinical Score
    99%
    Editor's Pick
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...New CBD users
  • Summary

    Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.

    Pro's
    Cons's
     Mid-strength  No other flavors
     Natural peppermint flavor
     Made from 100% organic and natural ingredients
  • Features
    Discount pricing available? 20% Off Coupon Code: CBDCLINICALS
    Source
    Source of Hemp
    Kentucky, USA & North Carolina, USA
    Form Oil Tincture
    Ingredients Organic Hemp Seed Oil, Full Spectrum CBD Oil
    Type
    Type of CBD
    Full Spectrum
    Extraction
    Extraction Method
    Moonshine extraction method
    How to take it Under tongue
    Potency
    Potency - CBD Per Bottle
    750 mg per bottle
    Carrier Oil Organic Hemp Seed Oil
    Concentration
    CBD Concentration Per Serving
    25mg of CBD per dropper full (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
    Flavours Peppermint
    Price Range $89 ($75.65 for subscriptions, 15% discount from regular price)
    $/mg CBD
    Price ($/mg)
    $0.12/mg ($0.10/mg with subscription)
    Shipping
    Shipping/Time to delivery
    2-4 business days (first class USPS)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants Organic, Non-GMO, no pesticides, no herbicides, no solvents or chemical fertilizers, No preservatives or sweeteners
    Allergens Vegan, Gluten free
    Refund policy Within 30 days
    Recommended for New CBD users
    Countries served USA only (all 50 states)
Check Latest Prices

Best Organic

NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil

Perfect for anyone who are looking for CBD products that promote a healthy body and mind.
NuLeaf Naturals 900mg Full Spectrum Hemp CBD Oil
  • Overall Clinical Score
    99%
    Best Organic
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Health-conscious persons
  • Summary

    Natural remedy for various illnesses. NuLeaf Naturals’ CBD oil is a whole-plant extract containing a full spectrum of naturally occurring synergistic cannabinoids and terpenes.

    Pro's
    Cons's
     Pure CBD hemp  No other flavors
     All natural
     Approximately 300 drops total
  • Features
    Discount pricing available? 20% Off Coupon Code: CBDCLINICALS20
    Source
    Source of Hemp
    Colorado, USA
    Form Oil Tincture
    Ingredients Full Spectrum Hemp Extract, Organic Virgin Hemp Seed Oil
    Type
    Type of CBD
    Full Spectrum CBD
    Extraction
    Extraction Method
    CO2 Method
    How to take it Under the tongue for approximately 30 seconds before swallowing
    Potency
    Potency - CBD Per Bottle
    900mg per bottle
    Carrier Oil Organic Hemp Oil
    Concentration
    CBD Concentration Per Serving
    60mg per dropper full (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
    Flavours Natural
    Price Range $99 - $434
    $/mg CBD
    Price ($/mg)
    $0.08 - $0.13
    Shipping
    Shipping/Time to delivery
    2-3 Days via USPS
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants No additives or preservatives, Non-GMO, NO herbicides, pesticides, or chemical fertilizers
    Allergens Not specified
    Refund policy Within 30 days
    Recommended for Health-conscious persons
    Countries served USA (all 50 states) and over 40 countries including Australia, Azerbaijan, Beliza, Bosnia & Herzegovina, Brazil, Chile, China, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Ireland, Israel, Japan, Latvia, Lebanon, Lithuania, Macao, Malaysia, Malta, Netherlands, New Zealand, Oman, Paraguay, Poland, Portugal, Saudi Arabia, Serbia, Singapore, South Korea, Sweden, Switzerland, United Arab Emirates, United Kingdom, Uruguay, and many more.
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Best Customer Service

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4x the strength of a regular cbd oil
Sabaidee Super Good Vibes CBD Oil
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  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
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    Perfect for...Patients who are looking for serious CBD oil support
  • Summary

    Super Good Vibes CBD Oil provides the purest and highest quality Cannabidiol (CBD) on the market as well as other high quality phytocannabinoids, terpenes, vitamins, omega fatty acids, trace minerals, and other beneficial for your health elements, which all work together to provide benefits.

    Pro's
    Cons's
     Extra strong  No other flavors
     Significant benefits with just a few drops
     100% Natural ingredients
  • Features
    Discount pricing available? 15% Off Coupon Code: CBDCLINICALS15
    Source
    Source of Hemp
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    Form Oil Tincture
    Ingredients Cannabidiol (CBD), Coconut Medium-chain triglycerides (MCT) Oil, Peppermint oil
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2-extraction
    How to take it Using 1-3 servings per day as needed is a good start to determine how much you need
    Potency
    Potency - CBD Per Bottle
    1000 mg per bottle
    Carrier Oil Coconut MCT Oil
    Concentration
    CBD Concentration Per Serving
    33.5 mg per dropper (1ml)
    Drug Test Contains 0.3% THC but there is a chance you may test positive for marijuana
    Flavours Peppermint
    Price Range Single Bottle - $119.95, 2-Pack - $109.97 each, 3-Pack - $98.31 each, 6-Pack - $79.99 each
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    Shipping/Time to delivery
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    Lab Tests
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    Third Party Lab Tested post formulation for safety and potency, available on website
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    Refund policy Within 30 days
    Recommended for Patients who are looking for serious CBD oil support
    Countries served USA only (all 50 states)
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Best Natural Alternative

cbdMD CBD Oil Tincture Natural 1500mg

Uses USA hemp that is grown on non-GMO farms, and is both vegan and gluten-free
cbdMD CBD Oil Tincture Natural 1500mg
  • Overall Clinical Score
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    Best Natural Alternative
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Daily CBD oil users
  • Summary

    cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.

    Pro's
    Cons's
     Various delicious flavors to choose from  cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options
     Has vegan, organic, and gluten-free ingredients
     Free shipping for this particular product within USA
     World-class customer service team
  • Features
    Discount pricing available? 15% Off Coupon Code: cbdMD15
    Source
    Source of Hemp
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    Form Oil Tincture
    Ingredients Cannabidiol (CBD), MCT Oil, and Flavoring
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2 extraction method
    How to take it Under tongue
    Potency
    Potency - CBD Per Bottle
    1500mg per bottle
    Carrier Oil Organic Coconut MCT Oil
    Concentration
    CBD Concentration Per Serving
    50mg per dropper full (1ml)
    Drug Test Containing less than 0.3% THC, there are still trace amounts
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    Price Range $99.99
    $/mg CBD
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    Shipping/Time to delivery
    2-5 Business days (via Fedex)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants 100% organic, non-GMO, and vegan-certified
    Allergens Vegan, Gluten free
    Refund policy Within 30 days
    Recommended for Daily CBD oil users
    Countries served USA only (all 50 states)
Check Latest Prices

Conclusion

Metformin is an FDA-approved medication that is prescribed to individuals who have type 2 diabetes. It is often given on its own or with other prescription drugs to manage high blood glucose levels in the body.

The said medication can effectively prevent diabetes in high-risk individuals, while also reducing most of its complications. There may be adverse reactions associated with metformin use, but most reports mention that these are only minor considering its benefits.

Cannabidiol, also known as CBD, is said to contain cannabinoid receptors that can benefit people with diabetes. Several clinical trials on mice and rats reveal the antihyperglycemic potential of the phytocannabinoid.

Since metformin can treat diabetes effectively, most people consider taking it together with the healing properties of CBD edibles. There are no studies, however, that prove these two products can be used together.

In fact, they may not work well with each other due to how the body processes both metformin and CBD products. Lactic acidosis is the most severe side effect that a person may experience with metformin overdose, which has symptoms such as dizziness, muscle pain, chills, and difficulty in breathing.

As no clear indication of whether metformin users are at risk or not when using CBD, it is best to avoid using them together for now. At the very least, seeking medical advice from a healthcare provider knowledgeable in the cannabis plant may be a possible option.

Insulin may be a potential antihyperglycemic agent that can work well in conjunction with CBD oil help. A placebo-controlled study in 2016 shows that CBD is capable of lowering insulin resistance while improving the effects of insulin in the body.

In 2018, a study on rats revealed that low tincture doses of CBD could enhance glucose uptake, improve weight loss, and reverse insulin resistance in the subjects. All these are potential indications that CBD can be used together with insulin to improve its effectiveness.


  1. Corcoran C, Jacobs TF. Metformin. [Updated 2020 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
  2. Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658‐664.
  3. Lehmann C, Fisher NB, Tugwell B, Szczesniak A, Kelly M, Zhou J. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes. Clin Hemorheol Microcirc. 2016;64(4):655‐662. doi:10.3233/CH-168021
  4. Ramlugon S, Levendal RA, Frost CL. Time-dependent effect of phytocannabinoid treatments in fat cells. Phytother Res. 2018;32(6):1080‐1089. doi:10.1002/ptr.6047
  5. Khalid A. Jadoon, Stuart H. Ratcliffe, David A. Barrett, E. Louise Thomas, Colin Stott, Jimmy D. Bell, Saoirse E. O’Sullivan, Garry D. Tan. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care Oct 2016, 39 (10) 1777-1786; DOI: 10.2337/dc16-0650.
  6. Corcoran C. et al. op. cit.
  7. Nasri H. et al. op. cit.
  8. Lehmann C. et al. op. cit.
  9. Ramlugon S. et al. op. cit.
  10. Zendulka O, Dovrtělová G, Nosková K, et al. Cannabinoids and Cytochrome P450 Interactions. Curr Drug Metab. 2016;17(3):206‐226. doi:10.2174/1389200217666151210142051
  11. Grayson L, Vines B, Nichol K, Szaflarski JP; UAB CBD Program. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10‐11. Published 2017 Oct 12. doi:10.1016/j.ebcr.2017.10.001
  12. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516‐525. doi:10.1016/j.biopsych.2015.07.028
  13. Nasri H. et al. op. cit.
  14. Khalid A. et al. op. cit.
  15. Ramlugon S. et al. op. cit.
  16. Barré-Sinoussi F, Montagutelli X. Animal models are essential to biological research: issues and perspectives. Future Sci OA. 2015;1(4):FSO63. Published 2015 Nov 1. doi:10.4155/fso.15.63
  17. Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39(2):143‐151. doi:10.1080/08916930500356674
  18. Lehmann C. et al. op. cit.
  19. Santiago AN, Mori MA, Guimarães FS, Milani H, Weffort de Oliveira RM. Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats. Neurotox Res. 2019;35(2):463‐474. doi:10.1007/s12640-018-9972-5
  20. Dawson D., Conlon C. Case Study: Metformin-Associated Lactic Acidosis. Diabetes Care Aug 2003, 26 (8) 2471-2472; DOI: 10.2337/diacare.26.8.2471
  21. Blonde L., Dailey G., Jabbour S., Reasner C. Mills D. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Accepted 23 Jan 2004, Published online: 05 Mar 2004. https://doi.org/10.1185/030079904125003278

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Metformin Use During the First Trimester of Pregnancy – Is it safe?

QUESTION

A pregnant patient with polycystic ovary syndrome asked me whether continuing metformin, which she was taking to treat infertility before her pregnancy, was safe for her fetus. She had heard that metformin is a “drug for diabetes.” How safe is metformin use during the first trimester of pregnancy and beyond?

ANSWER

Despite the traditional response that all oral hypoglycemic agents are absolutely contraindicated during pregnancy, evidence that metformin is probably safe during the first trimester of pregnancy and beyond is accumulating.

Metformin is currently approved by the United States Food and Drug Administration for treatment of type 2 diabetes. The most current product monograph still lists pregnancy as a contraindication to metformin; however, in both Canada and the United States, its off-label use in treatment of infertility caused by PCOS is growing.

Metformin is known to facilitate conception in women who have oligomenorrhoea and PCOS. Recent studies have suggested that metformin use during pregnancy decreases the high incidence of spontaneous abortion associated with PCOS (30% to 50%)9 and with gestational diabetes (31% in untreated women vs 3% in treated women).

Whether metformin causes teratogenicity in animals is controversial. Some animal studies found no evidence of teratogenicity at doses as high as 600 mg/kg daily. One study showed that metformin at doses similar to clinical in vivo levels had no direct toxic effects on mouse embryo development. 

Another study showed that, although exposure to both biguanides, phenformin and metformin, were associated with embryo death, phenformin has greater toxicity in mouse whole embryo culture, suggesting that metformin might be safer to use during pregnancy. 

Other studies, however, have suggested that metformin induces a low incidence of malformations in rats. For women taking metformin for PCOS, the question of teratogenicity remains challenging because it is difficult to clarify whether the teratogenic potential is subsequent to poor glycemic control or subsequent to the direct actions of the oral hypoglycemic drug itself.

Results of Metformin Use During the First Trimester of Pregnancy

No evidence shows that metformin use during the first trimester of pregnancy in women with PCOS is associated with increased risk of malformations.

Most of the studies applicable to PCOS restricted exposure to the first trimester, i.e., metformin was discontinued as soon as pregnancy was diagnosed. Evidence beyond the first trimester is anecdotal at this point.

Large well-controlled studies of humans are needed. For women with non-insulin-dependent diabetes mellitus, insulin is still considered the treatment of choice during pregnancy, although glyburide has been shown not to cross the human placenta.

Use of Hypoglycemic Drugs During Lactation

QUESTION

My patient was taking glipizide (an oral sulfonylurea) for type 2 diabetes. Now she is pregnant and taking insulin instead. She is very anxious to return to her previous treatment immediately after delivery because of the pain and hurdles associated with the administration of insulin. 

Can sulfonylureas cross into human milk and, if so, is it safe for her to breastfeed her infant?

ANSWER

The exposure of infants to second-generation sulfonylureas (eg, glipizide, glyburide) through breast milk is expected to be minimal, based on the limited data available. 

Women with type 2 diabetes treated with sulfonylureas should not be discouraged from breastfeeding. The benefits of breastfeeding greatly outweigh the risks of these medications, if any. The baby should, however, be monitored for signs of hypoglycemia.

Effects of the Use of Hypoglycemic Drugs During Lactation

First-generation sulfonylureas have, to a limited extent, been shown to cross into breast milk. Tolbutamide is excreted into breast milk in small amounts (less than 0.5% of the maternal weight-adjusted dose). 

A 500-mg dose of tolbutamide twice daily produced milk levels of 3 and 18 µg/mL in 2 patients, with milk-to-plasma ratios of 0.09 and 0.40, respectively.8 In 1 patient, chlorpropamide was found in breast milk at concentrations of 5 µg/mL (approximately 10% of the maternal weight-adjusted dose) after a 500-mg maternal oral dose.

No clinical effects to the exposed infants were reported. Transfer of second-generation sulfonylureas into breast milk has been studied, with similar results.

Metformin and the Use of Hypoglycemic Drugs During Lactation

Metformin is a widely used oral, biguanide hypoglycemic drug for the management of type 2 diabetes. Metformin stimulates glucose uptake in the liver and peripheral tissues and decreases hepatic glucose production. These actions are the result of an enhanced tissue response to insulin and therefore require the presence of insulin. Metformin is not expected to cause hypoglycemia.

Final Thoughts on the Use of Hypoglycemic Drugs During Lactation

The available data suggest that the levels of glyburide and glipizide in milk are negligible and would not be expected to cause adverse effects in breastfed infants; however, as data are based on a single study with a limited sample size, monitoring of the breastfed infant for signs of hypoglycemia is advisable during maternal therapy with any of these agents.

Treatment with metformin during lactation is unlikely to lead to toxicity in the breastfed infant. Given the safety profile of metformin, as compared with sulfonylureas, it is advisable to consider metformin as first-line treatment during lactation if this drug is appropriate for the particular patient. Nevertheless, second-generation sulfonylureas are also likely to be safe during lactation.

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