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The Mechanism of Goat's Rue or French Lilac in the Treatment of Diabetes Mellitus


  • Goat's Rue or French Lilac (Galega officinalis) is a flowering plant containing guanidine that has been used to treat diabetes since the early 1900's.
  • It was guanidine from which metformin (Glucophage) was derived and has become one of the primary treatments of type 2 diabetes mellitus and thus, most likely has a similar mechanism of action to metformin (inhibiting the excessive basal rates of hepatic gluconeogenesis).
  • Guanidine was associated with significant toxicities, including increasing lactic acid levels that prevented its further use in clinical practice.
  • While guanidine containing supplements have glucose lowering properties, the toxicity profile outweighs any potential benefits provided and should not generally be used or recommended.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: August 2015


  • Goat's Rue or French Lilac (Galega officinalis) is a flowering plant that has been used to treat diabetes since the early 1900's.1,2  The active ingredient is known to be guanidine and initially marketed under the trade name Synthalin.2,3,4,5  It was guanidine from which the most widely used and cost-effective prescription medication for the treatment of type 2 diabetes mellitus, metformin (Glucophage), was derived.2 

    It is well known that patients with type 2 diabetes mellitus (T2DM) are characterized as having insulin resistance, a decrease in insulin mediated glucose uptake by peripheral tissues and excessive basal rates of hepatic gluconeogenesis.6  An impairment in peripheral glucose uptake and suppression of gluconeogenesis both contribute to worsening postprandial (post-meal) hyperglycemia, whereas excessive basal rates of hepatic gluconeogenesis primarily contributes to the worsening of fasting glucose levels.  Since the guanidine found in Galega officinalis was the precursor to metformin, guanidine may in part exert its glucose lowering properties through an inhibition of the excessive basal rates of hepatic gluconeogenesis.3,4,5,7  In addition, it is plausible, that guanidine slows down this process by decreasing the ability of glucose 6-phosphate generated from glycogen breakdown to be converted to glucose through an inhibition of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase as seen with its derivative, metformin.4,5,8,9

    Unfortunately, guanidine compounds have been associated with significant toxicities limiting their further use in clinical practice.  The reported toxicities include kidney and liver damage, hypotension, ataxia, and  seizures.3,4,5,10  Unfortunately the limited science on guanidine in the early 1900's and its toxicity profile preventing its further use did not allow for a clear determination of reasons for the toxicities.  However, many of these toxicities can also be seen with lactic acidosis.10  In fact, very early studies indicated increases in lactic acid production with guanidine.5  Interestingly, the derivatives of guanidine (metformin and phenformin) have been shown to inhibit complex I of the mitochondrial electron transport chain, thereby causing a back up in the TCA cycle (Kreb's Cycle) that forces the pyruvate generated from glycolysis to accumulate and thus be converted to lactate (lactic acid).  This preferential conversion of pyruvate to lactic acid is done to oxidize NADH back to NAD+ so that glycolysis can continue to generate at least 2 ATP to be used for energy.  Unfortunately, phenformin is more likely to do this compared to metformin and was the reason it was withdrawn from the U.S. and European markets. 

    It is likely that guanidine containing supplements are likely to increase the risk for lactic acidosis, as well as other toxicities not adequately characterized given drug class' history.  Clinicians should discourage the use of guanidine containing herbal medicinals for the above reasons.  If however, the patient does take them, it may be prudent to monitor blood glucose levels, chemistries for the presence of an anion gap or changes in renal function, liver enzymes, and signs/symptoms of lactic acidosis.


    1. Yeh GY, Eisenberg DM, Kaptchuk TJ et al. Systematic review of herbs and dietary supplements for glycemic control in diabetes.  Diabetes Care   2003;26:1277-94.       
    2. Dey L, Attele AS, Yuan CS.  Alternative therapies for type 2 diabetes.  Altern Med Rev   2002;7:45-58.
    3. Samuelsen GS.  An investigation of the toxicity and hypoglycemic effect of several guanidine compounds.  J Pharmacol Exp Ther  1935;51:17-24.
    4. Blatherwick NR, Sahyun M, Hill E.  Some effects of synthalin on metabolism.  J Biol Chem   1927;75:671-82.
    5. Bodo R, Marks HP. The relation of synthalin to carbohydrate metabolism.  J Physiol.  1928;65:83-99.
    6. Monnier L, Colette C, Owens DR.  Type 2 diabetes: a well-characterised but suboptimally controlled disease.  Can we bridge the divide?  Diabetes Metab  2008;34:207-16.
    7. Cusi K, Consoli A, DeFronzo RA.  Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus.  J Clin Endocrinol Metab 1996;81:4059-67.
    8. Mithieux G, Guignot L, Bordet JC et al.  Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high fat diet.  Diabetes  2002;51:139-43.
    9. Shaw RJ, Lamia KA, Vasquez D et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutics effects of metformin.  Science  2005;310:1642-6.
    10. Kwong SC, Brubacher J.  Phenformin and lactic acidosis: a case report and review.  J Emerg Med  1998;16:881-6.
    11. Kumar A, Nugent K, Kalakunja A et al.  Severe acidosis in a patient with type 2 diabetes mellitus, hypertension and renal failure.  CHEST  2003;123:1726-9.
    12. Luft D, Schmulling RM, Eggstein M.  Lactic acidosis in biguanide-treated diabetics: a review of 330 cases.  Diabetologia  1978;14:75-87.

MESH Terms & Keywords

  • Goats Rue, French lilac, Diabetes Mellitus, Guanidine, Type 2 Diabetes Mellitus, Herbal Supplements for Diabetes Mellitus