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Metformin

Also indexed as: Glucophage®

Metformin is a drug used to lower blood sugar levels in people with non-insulin-dependent (type 2) diabetes.

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 Foods and Other Compounds

Food
Food interferes with metformin absorption.8 9 10 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.11 People taking metformin should avoid alcohol or consult with their doctor before consuming alcohol.

Summary of Interactions for Metformin

Depletion or interference Folic acid*
Vitamin B12
Adverse interaction None known
Side effect reduction/prevention Calcium
Supportive interaction None known
Reduced drug absorption/bioavailability Guar gum*
Other (see text) DHEA
Magnesium

For the convenience of the reader, the information in the summary is categorized as follows: “Depletion or interference” indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. “Adverse interaction” indicates that the supplement or herb used together with the drug may result in undesirable effects. “Side effect reduction/prevention” indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. “Supportive interaction” indicates the supplement or herb may support or aid the function of the drug. “Reduced drug absorption/bioavailability” indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

References:

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. 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.

9. 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.

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

11. 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.