METFORMIN

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Safetychecker Summary for Metformin
(for details about the summarized interactions, read the full article)

May be Beneficial: Depletion or interference—The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.	Folic acid* Vitamin B12
May be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.	Calcium
Avoid: Reduced drug absorption/bioavailability—Avoid these supplements when taking this medication since the supplement may decrease the absorption and/or activity of the medication in the body.	Guar gum*
Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	Ginkgo biloba
Check: Other—Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details.	DHEA Magnesium
Supportive interaction	None known

Interactions with Dietary Supplements

Dehydroepiandrosterone (DHEA)
Metformin has been reported to increase blood levels of DHEA-sulfate in at least two studies.^{1 2}

Folic acid and Vitamin B12
Metformin therapy has been shown to deplete vitamin B12 and sometimes, but not always,³ folic acid as well.⁴ This depletion occurs through the interruption of a calcium-dependent mechanism. Supplementation with calcium has reversed this effect in a clinical trial.⁵ People taking metformin should supplement vitamin B12 and folic acid or ask their doctor to monitor folic acid and vitamin B12 levels.

Magnesium
In a study of patients with poorly controlled type 2 diabetes, low blood levels of magnesium, and high urine magnesium loss, metformin therapy was associated with reduced urinary magnesium losses but no change in low blood levels of magnesium.⁶ Whether this interaction has clinical importance remains unclear.

Guar gum
In a small, controlled study, guar gum plus metformin slowed the rate of metformin absorption.⁷ In people with diabetes this interaction could reduce the blood sugar–lowering effectiveness of metformin. Until more is known, metformin should be taken two hours before or two hours after guar gum–containing supplements. It remains unclear whether the small amounts of guar gum found in many processed foods is enough to significantly affect metformin absorption.

Interactions with Herbs

Ginkgo biloba
In a preliminary trial, administration of Ginkgo biloba extract (120 mg per day) for three months to patients with type 2 diabetes who were taking oral anti-diabetes medication resulted in a significant worsening of glucose tolerance. Ginkgo did not impair glucose tolerance in individuals whose diabetes was controlled by diet.⁸ Individuals taking oral anti-diabetes medication should consult a doctor before taking Ginkgo biloba.

Interactions with Foods and Other Compounds

Food
Food interferes with metformin absorption.^{9 10 11} Taking metformin with food can reduce the absorption of the drug. Therefore, metformin should be taken an hour before or two hours after a meal unless stomach upset occurs.

Alcohol
Lactic acidosis is a rare but serious side effect of metformin. Alcohol increases the production of lactic acid caused by metformin, increasing the risk of lactic acidosis.¹² People taking metformin should avoid alcohol or consult with their doctor before consuming alcohol.

1. Nestler JE, Beer NA, Jakubowicz DJ, Beer RM. Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men. J Clin Endocrinol Metab 1994;78:549–54.

2. Crave JC, Fimbel S, Lejeune H, et al. Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab 1995;80:2057–62.

3. Carpentier JL, Bury J, Luyckx A, Lefebvre P. Vitamin B 12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187–90.

4. Carlsen SM, Folling I, Grill V, et al. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521–7.

5. Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227–9.

6. McBain AM, Brown IR, Menzies DG, Campbell IW. Effects of improved glycaemic control on calcium and magnesium homeostasis in type II diabetes. J Clin Pathol 1988;41:933–5.

7. Gin H, Orgerie MB, Aubertin J. The influence of Guar gum on absorption of metformin from the gut in healthy volunteers. Horm Metab Res 1989;21:81–3.

8. Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract (EGb 761) on pancreatic beta-cell function in response to glucose loading in individuals with non-insulin-dependent diabetes mellitus. J Clin Pharmacol 2001;41:600–11.

9. Cardot JM, Saffar F, Aiache JM. Influence of food on glycemia, insulin, C-peptide and glucagon levels in diabetic patients treated with antidiabetic metformin at steady-state. Methods Find Exp Clin Pharmacol 1997;19:715–21.

10. Sambol NC, Brookes LG, Chiang J, et al. Food intake and dosage level, but not tablet vs solution dosage form, affect the absorption of metformin HCl in man. Br J Clin Pharmacol 1996;42:510–2.

11. Sifton DW, ed. Physicians Desk Reference, Montvale, NJ: Medical Economics Co., Inc., 2000, 831–5.

12. Threlkeld DS, ed. Hormones, Antidiabetic Agents, Biguanides, Metformin HCl. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, May 1995, 130n–130u.

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Copyright © 2002 Healthnotes, Inc.  All rights reserved. www.healthnotes.com

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2003.

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