Sulfonylureas

Summary

drug class: Sulfonylureas

generic and trade names:
First generation Sulfonylureas:
• Acetoheximide: Dymelor®
• Chlorpropamide: Diabinase®
• Tolazamide: Tolinase®
• Tolbutamide: Ornase®

Second generation sulfonylureas:
• Glipizide: Glucotrol®
Glyburide: DiaBeta®, Micronase®

Glimepiride (Amaryl®) represents a new type of sulfonylurea.

type of drug: Oral hypoglycemic agents.

used to treat: used to treat: Hyperglycemia in non-insulin-dependent (NIDDM or Type II) diabetes mellitus which is stable, mild, and nonketosis-prone and cannot be controlled solely by proper dietary management, exercise and weight reduction.

mechanism: Sulfonylureas work by stimulating insulin production, sensitizing insulin receptors, and inhibiting the production of glucose by the liver.

adverse effects: The primary side effect of sulfonylurea class drugs is hypoglycemia (low blood sugar). Hypoglycemia is more likely to occur when the caloric intake is inadequate or after strenuous or prolonged exercise.

overview of interactions:

• nutrient affecting drug performance and toxicity: Niacin

• nutrient affecting drug performance and toxicity: Vitamin E

• nutrient affecting drug toxicity: Lithium

• nutrient affecting drug toxicity: Magnesium

• nutrient affected by drug: Sodium

• substance affecting drug toxicity: Alcohol

• herbal constituent theoretically affecting drug performance and toxicity: Coumarin-containing Plants

Common herbs containing significant coumarin constituents:
Aesculus hippocastanum (Horse Chestnut seed)
Ammi visnaga (Visnaga)
Asperula odorata (Sweet Woodruff)
Galium odoratum (Bedstraw)
Melilotus spp. (Sweet Clover)
Trifolium pratense (Red Clover)

• foods/herbs affecting drug performance: Hypoglycemic Herbs including Allium cepa (Onion bulbs), Allium sativum (Garlic cloves), Arctium lappa (Burdock roots), Cucumis sativus (Cucumber fruit), Cuminum cyminum (Cumin seed), Eleutherococcus senticosus (Siberian ginseng), Gymnema sylvestre (Gymnema leaves), Momordica charantia (Bitter melon fruit), Olea europaea (Olive leaves), Oplopanax horridum (Devil’s club root bark), Opuntia spp. (Prickly pear stems and fruit), Panax ginseng (Chinese Ginseng root), Spinacea oleracea (Spinach leaves), Syzygium jambolanum (Jambul seeds), Taraxacum officinale (Dandelion plant), Trigonella foenum-graecum (Fenugreek seeds), Triticum sativum (Wheat leaves), Turnera diffusa (Damiana leaves), Urtica dioica (Stinging nettle plant), Vaccinium myrtillus (Bilberry leaves), Zea mays (Corn silk) and, to a lesser degree, assorted foods such as Brassica oleracia (Cabbage), and a variety of other green leafy vegetables, beans and tubers.

• herbs theoretically affecting drug performance: Hyperglycemic Herbs such as Apium graveolens (Celery seed), Bupleurum falcatum (Bupleurum), Centella asiatica (Gotu kola), and Rosmarinus officinalis (Rosemary).

• herb affecting drug performance: Aloe vera (Aloe)

• nutrient affecting drug performance: Cyamopsis tetragonolobus (Guar gum) (Guar gum) (Guar gum)

• herbal preparation affecting drug performance: D-400

Interactions

nutrient affecting drug performance and toxicity: Niacin

• mechanism: Supplemental use of niacin may result in increased blood glucose levels.
(Drug Evaluations Subscription. 1994.)

• nutritional concerns: Individuals taking a sulfonylurea drugs may need to increase their dosage if they take niacin concomitantly. Before starting any supplementation with niacin it would be advisable to consult with the prescribing physician and/or a nutritionally oriented healthcare professional.

nutrient affecting drug performance and toxicity: Vitamin E

• mechanism: Vitamin E supplements suppress hemoglobin glycation. Consequently, glycemic control may appear falsely exaggerated.
(Drug Evaluations Subscription. Winter, 1994.)

nutrient affecting drug toxicity: Lithium

• mechanism: Lithium administration may increase the risk of hypoglycemia from sulfonylureas.
(Drug Evaluations Subscription. Winter, 1994.).

nutrient affecting drug toxicity: Magnesium

• mechanism: Magnesium hydroxide administration may increase the risk of hypoglycemia from sulfonylureas.
(Drug Evaluations Subscription. Winter, 1994; Schwanstecher M, et al. Naunyn Schmiedebergs Arch Pharmacol 1991 Jan;343(1):83-89.)

nutrient affected by drug: Sodium

• mechanism: Hyponatremia has been observed in 6-10% of diabetics treated with chlorpropamide. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has occasionally occurred with chlorpropamide. SIADH is characterized by excessive water retention and hyponatremia, low serum osmolality and high urine osmolality. These adverse effects have been reported most commonly in the elderly and patients with congestive heart failure or with hepatic cirrhosis, or with individuals taking diuretics.
(Berger W. Horm Metab Res Suppl 1985;15:111-115.)

substance affecting drug toxicity: Alcohol

• mechanism: Individuals taking sulfonylureas have been known to develop an intolerance to alcohol which can manifest as a disulfiram-like reaction: flushing, sensation of warmth, giddiness, nausea and occasionally tachycardia. Among the sulfonylureas, chlorpropamide has the most propensity to induce this type of reaction. Alcohol ingestion, by individuals taking sulfonylureas, has also been associated with unpredictable fluctuations in serum glucose levels, especially hypoglycemia.

• dietary concerns: Individuals taking sulfonylurea class drugs should avoid consuming alcohol while taking the prescription.

herbal constituent theoretically affecting drug performance and toxicity: Coumarin-containing Plants

• Common herbs containing significant coumarin constituents:
Aesculus hippocastanum (Horse Chestnut seed)
Ammi visnaga (Visnaga)
Asperula odorata (Sweet Woodruff)
Galium odoratum (Bedstraw)
Melilotus spp. (Sweet Clover)
Trifolium pratense (Red Clover)

• mechanism: Anticoagulant herbs, especially those containing coumarin, when administered with sulfonylureas, could potentially induce a transient increase in plasma concentrations of both substances. Theoretically, increased hepatic metabolism of sulfonylureas and decreased anticoagulant concentrations may occur with continued usage. However, coumarins in plants have not been shown to be blood thinning and there is no evidence they are fermented into bioactive dicoumarol.

• herbal concerns: Individuals taking sulfonylurea class drugs should avoid using herbs with anticoagulant action unless they have consulted with and are being monitored by their prescribing physician.

foods/herbs affecting drug performance: Hypoglycemic Herbs including Allium cepa (Onion bulbs), Allium sativum (Garlic cloves), Arctium lappa (Burdock roots), Cucumis sativus (Cucumber fruit), Cuminum cyminum (Cumin seed), Eleutherococcus senticosus (Siberian ginseng), Gymnema sylvestre (Gymnema leaves), Momordica charantia (Bitter melon fruit), Olea europaea (Olive leaves), Oplopanax horridum (Devil’s club root bark), Opuntia spp. (Prickly pear stems and fruit), Panax ginseng (Chinese Ginseng root), Spinacea oleracea (Spinach leaves), Syzygium jambolanum (Jambul seeds), Taraxacum officinale (Dandelion plant), Trigonella foenum-graecum (Fenugreek seeds), Triticum sativum (Wheat leaves), Turnera diffusa (Damiana leaves), Urtica dioica (Stinging nettle plant), Vaccinium myrtillus (Bilberry leaves), Zea mays (Corn silk) and, to a lesser degree, assorted foods such as Brassica oleracia (Cabbage), and a variety of other green leafy vegetables, beans and tubers.
(See complete listing at the end of the References.)

• mechanism: A large number of indigenous plants used as foods and medicines around the world are known for their ability to lower blood sugar levels through a variety of mechanisms. In some instances, the plant's hypoglycemic activity has been attributed to a particular extract or an identified constituent. These plants have often been used by practitioners of herbal medicine in treating individuals with non-insulin-dependent (type 2) diabetes. In such cases patient response must be carefully monitored and significant benefit can be gained from such therapies. However, the use of such herbs by type 1 (insulin-dependent) diabetics can be very risky and requires that such patients carefully monitor their blood sugar to prevent hypoglycemic and hyperglycemic episodes. Consultation with the prescribing physician is necessary and an integrative management of the case by conventional and herbal practitioners working together would be preferred. The shared goal would be to regulate the dosage of both types of medication and enable a smooth transition to lower dependence on insulin in cases where such is desirable and attainable. While hypoglycemic herbs may offer promise in the treatment of diabetes their combined effect with insulin, treatment is inherently disruptive and extreme caution must be exercised in order to promote a smooth transition, maintain suitable blood sugar levels and avoid insulin shock.

herbs theoretically affecting drug performance: Hyperglycemic Herbs such as Apium graveolens (Celery seed), Bupleurum falcatum (Bupleurum), Centella asiatica (Gotu kola), and Rosmarinus officinalis (Rosemary).

• mechanism: Herbs that exert a hyperglycemic effect via their insulin release inhibitory action could potentially raise blood sugar and hence be counterproductive in the treatment of diabetes. Apart from plants that are particularly high in sugars or other carbohydrates, only a few species of commonly-used plants demonstrate a high likelihood of causing adverse effects. However, of these only bupleurum is significantly hyperglycemic, and it is only transiently so. None of these herbs are serious elevators of blood sugar. Hence, any presumed interaction is largely speculative.
(Maloff BL, et al. Eur J Pharmacol. 1984 Sep 17;104(3-4):319-326.)

• nutritional support: Reducing the role of these foods in the diet can enhance the effect of both endogenous and pharmaceutical insulin and thereby improve blood sugar levels. Thorough and continued consultation with the prescribing physician and/or a nutritionally trained healthcare provider is an essential component of the successful prevention, management and treatment of any form of glucose metabolism problem, especially diabetes.

herb affecting drug performance: Aloe vera (Aloe)

• nutritional synergy/interaction: Several studies have found that Aloe vera can work as an effective agent in bringing down high blood glucose levels. If taken at the same time as glyburide or other sulfonylurea drugs, Aloe may reduce the dosage of the drug needed or, if unsupervised, could potentially cause blood glucose levels to drop excessively. In one study of diabetics who had been unresponsive to glyburide alone, significantly improved blood sugar and lipid levels resulted when one tablespoon of aloe juice twice daily was combined with the glyburide.
(Bunyapraphatsara, N, et al. Phytomed 1996;3:245-248.; Ghannam N, et al. Horm Res 1986;24(4):288-294.)

nutrient affecting drug performance: Cyamopsis tetragonolobus (Guar gum) (Guar gum) (Guar gum)

• nutritional synergy: The co-administration of guar gum significantly enhances the insulinogenic and blood glucose lowering effect of glyburide, and possibly other sulfonylurea drugs. If taken at the same time as the medication, guar gum may reduce the dosage of the drug needed or, if unsupervised, could potentially cause blood glucose levels to drop excessively.
(Huupponen R. Res Commun Chem Pathol Pharmacol 1986 Oct;54(1):137-140; Neugebauer G, et al. Beitr Infusionther Klin Ernahr 1983;12:40-47; Uusitupa M, et al. Int J Clin Pharmacol Ther Toxicol 1990 Apr;28(4):153-157.)

herbal preparation affecting drug performance: D-400

• nutritional synergy: In a study done with rabbits, an Ayurvedic "herbomineral preparation," called D-400, with proven antidiabetic activity, was combined with glibenclamide in alloxan-induced diabetic rabbits. Administration of D-400 significantly elevated plasma glibenclamide concentrations with simultaneous reduction of blood glucose.
(Sundaram R, et al. J Ethnopharmacol 1996 Dec;55(1):55-61.)


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Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

[No author given.] Drug Evaluations Subscription. Chicago: American Medical Association, Vol. II, Section 10, Chapter 3, Winter, 1994.

Berger W. Incidence of severe sideeffects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl 1985;15:111-115.
The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.

Bunyapraphatsara, N, Yongchaiyudha, S, Rungpitarangsi, V, Chokechaijaroenporn, O. Antidiabetic activity of Aloe vera L. juice. II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomed 1996;3:245-248.

Ghannam N, Kingston M, Al-Meshaal IA, Tariq M, Parman NS, Woodhouse N. The antidiabetic activity of aloes: preliminary clinical and experimental observations. Horm Res 1986;24(4):288-294.
Abstract: The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycaemic agent which lowers the blood glucose by as yet unknown mechanisms.

Huupponen R. The effect of guar gum on the acute metabolic response to glyburide. Res Commun Chem Pathol Pharmacol 1986 Oct;54(1):137-140.
Abstract: The effect of 5 g guar gum on the acute blood glucose, insulin and C-peptide response to 5 mg glyburide (HB 419) was investigated in 10 healthy volunteers after an overnight fast. The co-administration of guar gum significantly enhanced the insulinogenic and blood glucose lowering effect of glyburide.

Kolterman OG. The use of oral hypoglycemic agents in the management of type II diabetes. In: Sussman KE, Draznin B, James WE, eds. Clinical Guide to Diabetes Mellitus. New York: Alan R. Liss, Inc.;1987:33-45.

Maloff BL, Drake L, Riedy DK, Lockwood DH. Effects of sulfonylureas on the actions of insulin and insulin-mimickers: potentiation of stimulated hexose transport in adipocytes. Eur J Pharmacol. 1984 Sep 17;104(3-4):319-326.
Abstract: The sulfonylurea glyburide, a 'second-generation' oral hypoglycemic compound, was studied in vitro in order to determine its cellular mechanism of action in adipocytes prepared from cultured rat epididymal fat tissue. Glyburide treatment (1 microgram/ml) for 20 h did not alter insulin receptor number or affinity, or down-regulation by insulin. Biologic responses of these cells were measured in the presence of insulin or the oxidants Vitamin K5 and H2O2, which have insulin-like activity, but do not act through the binding portion of the receptor. 2-Deoxyglucose uptake was not significantly changed by exposure to glyburide alone. However, the sulfonylurea increased the insulin-stimulated or insulin-mimicker-activated uptake by approximately 30%. Insulin-stimulated glucose oxidation was also potentiated when glucose transport was rate limiting for metabolism. These findings extend our earlier observation that in adipose tissue the primary cellular mechanism of action of sulfonylureas is to potentiate insulin-stimulated hexose transport, and that this process may account for their hypoglycemic activity.

McCarty MF. Complementary measures for promoting insulin sensitivity in skeletal muscle. Med Hypotheses. 1998 Dec;51(6):451-64. (Review)

McCarty MF. Exploiting complementary therapeutic strategies for the treatment of type II diabetes and prevention of its complications. Med Hypotheses 1997 Aug;49(2):143-52.
Abstract: Impaired glycemic control in type II diabetes results from peripheral insulin resistance, hepatic insulin resistance, and a relative failure of beta cell function. Nutritional and pharmaceutical measures are now available for addressing each of these defects, presumably enabling a rational and highly effective clinical management of non-insulin-dependent diabetes mellitus. Peripheral insulin resistance, which usually responds to a very-low-fat diet, aerobic exercise training, and appropriate weight loss, can also treated with high-dose chromium picolinate, high-dose vitamin E, magnesium, soluble fiber, and possibly taurine; these measures appear likely to correct the diabetes-associated metabolic derangements of vascular smooth muscle, and thus lessen risk for macrovascular disease. Metformin's clinical efficacy is primarily reflective of reduced hepatic glucose output; this action should complement the benefits of peripheral insulin sensitizers. When these measures are not sufficient for optimal control, beta cell function can be boosted with second-generation sulfonylureas.

Mitra SK, Gopumadhavan S, Muralidhar TS, Seshadri SJ. Effect of D-400, a herbomineral formulation on liver glycogen content and microscopic structure of pancreas and liver in streptozotocin induced diabetes in rats. Indian J Exp Biol 1996 Oct;34(10):964-967.
Abstract: Streptozotocin induces severe and irreversible hyperglycaemia in experimental animals. The effect of oral administration of D-400 (1 gm/kg/day), a herbomineral formulation on streptozotocin induced-diabetes was studied in rats. Liver glycogen content was assayed biochemically on 2,4 and 8 weeks after D-400 treatment. Superoxide dismutase(SOD) activity of pancreatic islet cells was assessed on 8th week of D-400 treatment. The microscopic structure of pancreas and liver were examined in both control and treated animals. D-400 treatment showed progressive and significant increase in liver glycogen at 2,4 and 8 weeks respectively. Streptozotocin induced a decrease in pancreatic islet cell superoxide dismutase which was reversed by D-400 treatment for a period of 8 weeks. The free radical scavenging activity of D-400 may be attributed to shilajeet, one of its important ingredient. Streptozotocin induced histopathological changes in pancreas and liver was also partially reversed by D-400. The findings indicate that D-400 helps in improving the glycogen stores in the liver and prevents the streptozotocin induced damage through free radicals by increasing the islet cell superoxide dismutase activity.

Neugebauer G, Akpan W, Abshagen U. [Interaction of guar with glibenclamide and bezafibrate]. Beitr Infusionther Klin Ernahr 1983;12:40-47. [Article in German]

Roe DA. Drug and nutrient interactions in the elderly diabetic. Drug Nutr Interact. 1988;5(4):195-203. (Review)

Schwanstecher M, Loser S, Rietze I, Panten U. Phosphate and thiophosphate group donating adenine and guanine nucleotides inhibit glibenclamide binding to membranes from pancreatic islets. Naunyn Schmiedebergs Arch Pharmacol 1991 Jan;343(1):83-89.
Abstract: In microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine 5'-triphosphate (MgATP) increased the dissociation constant (KD) for binding of [3H]glibenclamide by sixfold. In the presence of Mg2+, not only ATP but also adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S), adenosine 5'-diphosphate (ADP), guanosine 5'-triphosphate (GTP), guanosine 5'-diphosphate (GDP), guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) and guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) inhibited binding of [3H]glibenclamide. These effects were not observed in the absence of Mg2+. Half maximally effective concentrations of the Mg complexes of ATP, ADP, ATP gamma S and GDP were 11.6, 19.0, 62.3 and 90.1 mumol/l, respectively. The non-hydrolyzable analogues adenosine 5'-(beta,gamma-imidotriphosphate) (AMP-PNP) and guanosine 5'-(beta,gamma-imidotriphosphate) (GMP-PNP) did not alter [3H]glibenclamide binding in the presence of Mg2+, MgADP acted much more slowly than MgATP and both MgADP and MgGDP did not inhibit [3H]glibenclamide binding when the concentrations of MgATP and MgGTP were kept low by the hexokinase reaction. Development of MgATP-induced inhibition of [3H]glibenclamide binding and dissociation of [3H]glibenclamide binding occurred at similar rates. However, the reversal of MgATP-induced inhibition of [3H]glibenclamide binding was slower than the association of [3H]glibenclamide with its binding site. Exogenous alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glibenclamide binding. MgATP enhanced displacement of [3H]glibenclamide binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert their effects by interaction with the same binding site at the sulfonylurea receptor and that protein phosphorylation modulates the affinity of the receptor.

Schwartz SL. Metformin: Cotherapy With Sulfonylureas Improves Control in Non-Insulin-Dependent Diabetes Mellitus. Advances In Therapy July/August 1997; 14(4):209-221
Abstract: The management goal of therapy for non-insulin-dependent diabetes mellitus (NIDDM) is the control of blood glucose as well as weight, hypertension, and lipid abnormalities. Diet and exercise comprise initial treatment in newly diagnosed, nonketotic, NIDDM patients who are otherwise relatively healthy. If these measures fail, oral antidiabetic therapy is generally the next option. Insulin, as a last-resort treatment, represents a major psychological step for most patients. Differing mechanisms of action of oral antidiabetic drugs can be used to achieve synergistic effects on blood glucose and postpone insulin therapy. Metformin/ sulfonylurea cotherapy controls hyperglycemia as effectively as insulin in many patients with sulfonylurea failure; metformin controls body weight, plasma lipid levels, and plasma insulin levels. This combination may constitute an effective next step after failure of monotherapy.

Sundaram R, Venkataranganna MV, Gopumadhavan S, Mitra SK. Interaction of a herbomineral preparation D-400, with oral hypoglycaemic drugs. J Ethnopharmacol 1996 Dec;55(1):55-61.
Abstract: D-400, a herbomineral preparation has proven antidiabetic activity in experimental models as well as in clinical trials. The possibility of concomitant use of this drug with sulphonylureas was explored in animal models. D-400 has been investigated for its interaction with oral hypoglycaemic agents namely, tolbutamide and glibenclamide in alloxan-induced diabetic rabbits. Administration of D-400 at a dose of 1 g/kg for 15 days significantly elevated plasma tolbutamide and glibenclamide concentrations with simultaneous reduction of blood glucose. Plasma tolbutamide and glibenclamide concentrations were significantly lowered after withdrawal of D-400 treatment. Elevation of plasma concentration of tolbutamide was observed only for the first 4 h after which it declined towards normal levels and no significant difference between D-400 treated and control group was observed at the end of 8 h. Significant elevation of plasma glibenclamide levels was observed at 2, 4 and 8 h with D-400 treatment. Incubation of D-400 with tolbutamide in plasma resulted in a significant increase in free tolbutamide levels.

Uusitupa M, Sodervik H, Silvasti M, Karttunen P. Effects of a gel forming dietary fiber, guar gum, on the absorption of glibenclamide and metabolic control and serum lipids in patients with non-insulin-dependent (type 2) diabetes. Int J Clin Pharmacol Ther Toxicol 1990 Apr;28(4):153-157.
Abstract: Nine patients with non-insulin-dependent diabetes (NIDDM) treated with glibenclamide (3.5 mg b.i.d.) participated in this randomized double-blind placebo controlled crossover study to evaluate the effects of granulated guar gum (5 g t.i.d. with meals) on the absorption of glibenclamide and metabolic control and serum lipids. Each treatment period lasted for 4 weeks, and there was a wash-out period of one week between the treatments. The fasting blood glucose (10.5 +/- 3.4 mmol/l on guar gum vs 11.3 +/- 3.7 mmol/l on placebo, p less than 0.05) and serum total cholesterol (5.9 +/- 1.4 mmol/l on guar gum vs 6.6 +/- 1.6 mmol/l on placebo; p less than 0.05) levels were lower after the treatment with guar gum than placebo. No significant differences were observed in serum triglycerides or HDL cholesterol between guar gum and placebo treatments. The administration of guar gum together with glibenclamide did not change significantly the maximum concentration (223 +/- 196 ng/ml on guar gum vs 184 +/- 138 ng/ml on placebo; n = 7, NS) or area under the curve (AUC0-6) [729 +/- 813 (ng/ml) X h on guar gum vs 560 +/- 513 (ng/ml) X h on placebo; NS] of glibenclamide. The fasting serum glibenclamide concentrations were similar at the end of the 4-week treatment period with guar gum and placebo. In conclusion, guar gum improved the metabolic control and decreased serum lipids of patients with NIDDM. In addition, guar gum ingested with glibenclamide did not interfere with the absorption of glibenclamide.

Addendum -

Hypoglycemic Herbs:
Adiantum capillus-veneris (Adiantum plant)
Allium cepa (Onion bulbs)
Allium sativum * (Garlic cloves)
Anacardium occidentale (Cashew leaves)
Arctium lappa (Burdock roots)
Argyreia cuneata (Rivea leaves)
Atriplex halimus (Salt bush leaves)
Bidens pilosa (Aceitilla plant)
Blighia sapida * (Akee apple seeds)
Brassica oleracia (Cabbage)
Catharanthus roseus (Madagascar periwinkle leaves)
Cecropia obtusifolia (Guarumo leaves and stem)
Coccinia grandis (Coccinia roots)
Coccinia indica (Ivy gourd)
Corchorus olitorius (Jute leaves)
Coutarea latiflora (Copalchi root bark)
Cucumis sativus (Cucumber fruit)
Cuminum cyminum (Cumin seed)
Eleutherococcus senticosus (Siberian ginseng)
Euphorbia prostrata
Ficus bengalensis * (Banyan stem bark)
Galega officinalis (Goat’s rue seeds)
Guazuma ulmifolia
Gymnema sylvestre (Gymnema leaves)
Hordeum vulgare (Barley sprouts)
Hygrophila auriculata (Barleria plant)
Lagerstroemia speciosa (Lagerstroemia leaves and ripe fruit)
Lepechinia caulescens
Lupinus albus (Lupin seeds)
Lycium barbarum (Box thorn leaves)
Lycopus virginicus (Bugleweed plant)
Momordica charantia (Bitter melon fruit)
Morus spp (Mulberry leaves)
Musa sapientum (Banana flowers and roots)
Nymphaea lotus (Lotus roots)
Ocimum sanctum (Sacred basil plant)
Olea europaea (Olive leaves)
Oplopanax horridum, also known as Fatsia horrida (Devil’s club root bark)
Opuntia spp. (Prickly pear stems and fruit)
Panax ginseng (Chinese Ginseng root)
Phaseolus vulgaris (Kidney bean, immature pods)
Polygonatum multflorum (Solomon’s seal root)
Psittacanthus calyculatus (Injerto flowers, leaves, and stem)
Rhizophora mangle
Rhus typhina (Staghorn sumach leaves)
Salpianthus arenarius (Catarinita flowers)
Sarcopoterium spinosum (Thorny burnet root bark)
Scoparia dulcis (Sweet broom plant)
Securinega virosa (Fluggea seeds)
Spinacea oleracea (Spinach leaves)
Syzygium jambolanum (Jambul seeds)
Taraxacum officinale (Dandelion plant)
Tecoma stans (Tronadora leaves)
Tinospora cordifolia (Gulancha plant)
Trigonella foenum-graecum (Fenugreek seeds)
Triticum sativum (Wheat leaves)
Turnera diffusa (Damiana leaves)
Urtica dioica (Stinging nettle plant)
Vaccinium myrtillus (Bilberry leaves)
Zea mays (Corn silk)
NOTE: * Indicates an herb having other side effects when taken alone in excessive doses.

(Adapted, with modifications derived from multiple source included above, from Brinker F. Herb Contraindications and Drug Interactions. pp. 104-105. Eclectic Institute: Sandy, OR, 1997.)