Metformin is an antihyperglycemic agent that improves glucose tolerance in patients with Type II Diabetes unable to control blood glucose levels with diet and exercise alone. Metformin is classified as a biguanide, and is sometimes combined with another class of antihyperglycemic medication called sulfonylureas such as glipizide or glyburide. It is also used in the treatment of metabolic syndrome and polycystic ovarian syndrome.(1) During the Middle Ages French Lilac (Galega officinalis) was used as a medicinal herb to reduce the increased urination associated with diabetes, and eventually became the source from which the biguanides were derived.(2)
Mechanism of Action: Metformin improves blood glucose levels via the following mechanisms: (1,3)
- decreases glucose production by the liver.
- decreases intestinal glucose absorption.
- increases the sensitivity of muscle and fat cells to insulin.
Multiple nutrient depletions are associated with metformin use:
| Vitamin/ Nutrient | Mechanism of Depletion | Suggested Action |
| Folic Acid | Declining B12 levels are often associated with a decline in folate/folic acid status and an elevation in homocysteine | Administer 400-800mcg folic acid daily, ideally with vitamins B12 and B6. (5) |
| Vitamin B12 | Significant evidence shows reduced Vitamin B12 absorption and low serum B12 with Metformin use. | 1000 – 5000 mcg daily supplementation is suggested. Vitamin B12 is best absorbed as a sublingual lozenge or intramuscular (IM) injection. (5,6,7) |
| Calcium | Uptake of the Vitamin B12 – intrinsic factor complex relies on calcium availability which is affected by Metformin. This B12 depletion can be reduced by additional calcium supplementation. | 500 – 750 mg of high quality calcium daily, preferably with additional magnesium and other minerals related to bone health. Avoid calcium carbonate. (5) |
| Chromium | Compromised chromium status is common and may contribute to insulin resistance and dysglycemia. Coadministration may enhance insulin activity and glucose control. | At least 200mcg daily with food. Monitor for symptoms of hypoglycemia (headache, dizziness, irritability.) |
| Magnesium | Magnesium is an important cofactor in carbohydrate and blood sugar metabolism and is often low in patients requiring Metformin. More studies are needed to assess these interactions. | Supplement 150 – 300mg magnesium citrate or glycinate and increase food sources: dark leafy greens, nuts, and whole unprocessed grains. |
To avoid drug nutrient depletions we recommend a vitamin B12 sublingual lozenge, daily folic acid, a high quality cal-mag like ALIVE Calcium by Nature’s Way, and additional chromium supplementation.
Ask our pharmacist or wellness specialist if:
- You have concerns about mineral/vitamin deficiency
- You would like more information about choosing an appropriate supplement.
References:
1. “Drug Reference and Patient Education: Metformin.” Clinical Pharmacology. Accessed 12/11/2014. http://www.clinicalpharmacology-ip.com.
2. “The Living Textbook of Diabetes. Biguanides.” Diapedia. Accessed 12/11/2014 http://www.diapedia.org/management/biguanides
3. Sirtori CR1, Pasik C. “Re-evaluation of A Biguanide, Metformin: Mechanism of Action and Tolerability.” Pharmacol Res. 30.3 1994 :187-228. http://www.ncbi.nlm.nih.gov/pubmed/7862618 Accessed Nov 06 2014
4. Lopez-Ridaura,Ruy MD, Willett, Walter C. MD, Rimm, Eric B. SCD, Liu, Simin MD, Stampfer, Meir J. MD, Manson, JoAnn E. MD and Hu, Frank B. MD. “Magnesium Intake and Risk of Type 2 Diabetes in Men and Women.” Department of Nutrition, Harvard School of Public Health. Diabetes Care 27.1 (2004 ): 134-140 http://care.diabetesjournals.org/content/27/1/134.full/Magnesium-Intake-and-Risk-of-Type-2-Diabetes-in-Men-and-Women Accessed 12/09/2014
5. Stargrove M, Treasure J, McKee D. Mosby Herb, Nutrient and Drug Interactions. Missouri: Elsevier Publishing, p.216-218, 465, 486-487, 499, 503-506, 580
6. Higdon, Jane .PhD. An Evidence Based Approach to Vitamins and Minerals. New York: Thieme, 2003 p. 212
7. “Drug Nutrient Depletion Checker.” National Standard. Accessed Nov 02 2014 https://naturalmedicines-therapeuticresearch-com.une.idm.oclc.org/checkers-tools/nutrient-depletion.aspx