Comparative evaluation of glipizide and fenugreek (Trigonella foenum-graecum) seeds as monotherapy and combination therapy on glycaemic control and lipid profile in patients with type 2 diabetes mellitus


  • Amandeep Singh Department of Pharmacology, Shri Guru Ram Rai Institute of Medical and Health Sciences, Patel Nagar, Dehradun, Uttarakhand, 248001, India
  • Jaswant Rai Department of Pharmacology,Government Medical College and Hospital, Amritsar, Punjab, 143001,India
  • Devinder Singh Mahajan Department of Medicine, Government Medical College and Hospital, Amritsar, Punjab, 143001, India



Glipizide, Fenugreek, Type 2 diabetes mellitus, Lipid profile, Glycaemic control


Background: Diabetes is commonly associated with dyslipidemia, which is one of the major risk factors of coronary heart disease (CHD), the leading cause of mortality in patients with type 2 diabetic. It is thus desirable that an anti-diabetic drug must provide good glycaemic control and in addition cause correction of dyslipidaemia, at the same time being safe. Fenugreek, a traditional drug has been found to have beneficial effect on glycaemic control as well as lipid profile and may be thus useful in such patients. The study was thus planned to further explore the effect of fenugreek seed on glycaemic control and lipid profile by comparing it with a standard anti-diabetic drug glipizide.

Methods: This 12 week, prospective, randomized, open-label, parallel group comparative study was conducted on 60 patients with type 2 diabetes. The patients were randomized to receive either glipizide 5 mg once daily (group A, n=20), fenugreek seed extract 500 mg twice a day (group B, n=20), or a combination of glipizide 2.5 mg and fenugreek seed extract 500 mg once daily (group C, n=20). The primary endpoint were the change in fasting blood glucose (FBG), glycated haemoglobin (HbA1c), and lipid profile from baseline after 12 weeks of treatment.

Results: A statistically significant decline in mean FBG levels                    (group A -33.97%, p<0.001; versus group B -24.62%, p<0.001; versus group C -29.96%, p<0.001), and in HbA1c levels (group A -12.98 %, p<0.0001; group B -9.38%, p<0.0001; and group C -10.62%, p<0.0001) was seen in all three treatment groups. Total cholesterol (TC) reduced non-significantly in group A (-0.98%, p=0.1982), whereas in group B (-5.66%, p<0.001) and group C (-3.87%, p<0.001) it decreased significantly. Non-significant reduction in plasma triglycerides (TG) were seen in group A (-0.74%, p=0.0669), and significant reductions were seen in both group B (-17.23%, p<0.001) and group C (-11.34%, p<0.001). Low density lipoproteins cholesterol (LDL-C) showed non-significant reductions in group A (-0.74%, p=0.5482), and significant reductions in both group B (-4.15%, p<0.001) and group C (-2.68%, p=0.0463). High-density lipoproteins cholesterol (HDL-C) showed non-significant changes in all three groups (group A -0.60%, p =0.1529; group B 0.65%, p=0.2072; and group C 0.76%, p = 0.0543). The adverse drug reactions seen were mild in nature and none of the patients was withdrawn from the study because of serious adverse drug reactions.

Conclusions: Monotherapy with fenugreek produced significant improvement in glycaemic control and dyslipidaemia. Glipizide monotherapy was more efficacious in controlling FBG and HbA1c levels than fenugreek monotherapy or in combination with fenugreek; glipizide monotherapy had no effect on lipid profile whereas fenugreek monotherapy was more efficacious in controlling dyslipidaemia than in combination with glipizide. Both drugs as monotherapy or in combination were well-tolerated by the patients.


Syvanne M, Taskinen MR. Lipids and lipoproteins as coronary risk factors in non-insulin-dependent diabetes mellitus. Lancet. 1997;350:120-3.

Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care. 1998;21:160-78.

Betteridge DJ. Dyslipidemia and diabetes. Practical Diab Int. 2001;18:201-7.

Betteridge DJ. Treating dyslipidaemia in the patients with type 2 diabetes. Eur Heart J. 2004;6:28-33.

Pyorala K, Laasko M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev. 1987;3(2):463-524.

Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, its risk factors and 12 year cardiovascular mortality for men screened in multiple risk factor intervention trial. Diabetes Care. 1993;16:434-44.

Ho JE, Paultre F, Mosca L. Is diabetes mellitus-a cardiovascular disease risk equivalent for fatal stroke in women? Data from the women pooling project. Stroke. 2003;34:2812-16.

McCarran P, Greenwood R, Elwood P. The incidence and aetiology of stroke in Carephilly and Speedwell collaborative studies II: risk factors for ischaemic stroke. Public Health. 2001;115:12-20.

Chun BY, Dobson AJ, Heller RF. The impact of diabetes on survival among patients with first myocardial infarction. Diabetes Care. 1997;20:704-08.

Wannamethee G, Whincup PH, Shaper AG, Walker Monotherapy, MacFarlane PW. Factors determining case fatality in myocardial infarction, who dies in a heart attack? Br Heart J. 1995;74:324-31.

DeJong, van Raak L, Kessels F, Lodder J. Glycaemic control, stroke subtype and mortality a follow-up study in 998 patients with a first cerebral infarct. J Clin Epidemiol. 2003;56:262-68.

Ginsberg HN. Diabetic dyslipidemia. In: Lebovitz HE, Editor. Therapy for diabetes mellitus and related disorders. 4th ed. Virginia: American Diabetes Association; 2004:293-309.

Haffner SM, Lehto S, Ronnemaa T. Mortality from coronary heart disease in subjects with type 2 diabetes and in non-diabetic subjects with and without prior myocardial infarction. N Eng J Med. 1998;339(4):229-34.

Adult treatment panel III. Executive summary of third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults. JAMA. 2001;285:2486-97.

Pyorala K, Pedersen TR, Kjekshus J, Faegeman O, Olsson AG, Thorgeirsson G. The scandinavian simvastatin survival study (4S) group: Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the scandinavian simvastatin survival study (4S). Diabetes Care. 1997;20:614-20.

Goldberg RB, Mellies MJ, Sacks FM. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation. 1998;98:2513-9.

The long-term intervention with pravastatin in ischaemic disease (lipid) study group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-57.

Haffner SM, Alexander CM, Cook TJ. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the scandinavian simvastatin survival study. Arch Intern Med. 1999;159:2661-7.

Heart protection study collaborative group: MRC/BHF heart protection study of cholesterol-lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet. 2002;360:7-22.

Tools of therapy. In: Burant CF, editor. Medical management of type 2 diabetes. 5th ed. Virginia: American Diabetes Association; 2004:27-77.

Indian council of medical research: guidelines for management of type 2 diabetes. 2005. Available at Accessed 2 March 2016.

Gupta A, Gupta R, Lal B. Effects of Trigonella foenum-graecum (Fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. JAPI. 2001;49:1057-61.

Sharma RD. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res. 1986;6:1353-64.

Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenum graecum L) on blood lipids, blood sugar, and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids. 1997;56(5):379-84.

Madar Z, Abel R, Samish S. Glucose lowering effect of fenugreek in non-insulin dependent diabetics. Eur J Clin Nutr. 1988;42:51-4.

Al Hobori M, Raman. Antidiabetic and hypochoesterolaemic effects of fenugreek. Phytother Res. 1998;12:233-42.

Shani J, Goldschmied A, Joseph B, Ahronson Z, Sulman FG. Hypoglycaemic effects of Trigonella foenum-graecum and Lupinus Termis (Leguminosae) Seeds and their major alkaloids in alloxan-diabetic and normal rats. Arch int Pharmacodyn. 1974;201:27-37.

Khosla, Gupta DD, Nagpal RK. Effect of Trigonella foenum-graecum (Fenugreek) on blood glucose in normal and diabetic rats. Indian J Physiol Pharmacol. 1995;39(2):173-4.

Ribes G, Sauvaire Y, Baccou, JC. Effects of fenugreek seeds on endocrine pancreatic secretions in dogs. Ann Nutr Metab.1984;28:37-43.

Sharma RD, Sarkar A, Hazra DK. Hypolipidaemic effect of fenugreek seeds: A chronic study in non-insulin dependent diabetic patients. Phytother Res 1996;10:332-4.

Jain V, Jain P, Sharma SW, Kakani R. Hypolipidaemic activity of syndrex, a hydroalcoholic extract of fenugreek seeds: Single blind clinical study. Int med j. 1995;89:1-4.

Prasanna M. Hypolipidemic effect of fenugreek: a clinical study. Indian J Pharmac. 2000;32:34-6.

Sharma RD, Raghuram TC, Rao VD. Hypolipidaemic effect of fenugreek seeds. A clinical study. Phytother Res. 1991;3:145-7.

Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr. 1999;53(4):3599-65.

Valette G, Sauvaire Y, Baccou JC, Ribes G. Hypocholesterolaemic effect of fenugreek seeds in Dogs. Atherosclerosis. 1984;50:105-11.

Sauvaire Y, Ribes G, Baccou JC, Mariani MML. Implication of steroid saponins and sapogenisins in the hypocholesterolaemic effect of fenugreek. Lipids. 1991;26:191-7.

Jefferson C. Fenugreek in diabetes management. UM school of pharmacy and allied health sciences drug information centre. 1999;3(7):1-2.

Ribes G, Sauvaire Y, Costa DC, Baccou JC, Mariani MML. Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs. Proc Soc Exp Biol Med. 1986;182:159-66.

Trinder P. Ann clin Biochem. 1969;6:24.

Trivelli LA, Ranney HM, Lai HT. Haemoglobin components in patients with diabetes mellitus. N Eng J med. 1971;284(7):353-7.

Bunn HF. Evaluation of glycosylated haemoglobin diabetic patients. Diabetes. 1981;30(7):613-7.

Allain CC, Poon LS, Chan CSG, Richmond W. Enzymatic determination of total serum cholesterol. Clin Chemistry. 1974;29:470-4.

Bucolo G, David H. Quantitative estimation of serum triglycerides by use of enzymes. Clin Chemistry. 1973;19:476-8.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chemistry. 1972;18:499-5.

Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus. A randomized controlled, double blind trial. J Am Med Assoc. 1998;280:1490-6.

Simonson DC, Korides IA, Feinglos M, Shamoon H, Fischette CT. Efficacy, safety and dose response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM; results of two multi-center randomized placebo-controlled chemical trials- The glipizide gastrointestinal therapeutic study group. Diabetes Care. 1997;20(4):597-606.

Sharma RD, Sarkar A, Hazra DK. Use of fenugreek seed powder in the management of non-insulin dependent diabetes mellitus. Nutr Res. 1996;16:1331-9.

Sharma RD, Raghuram TC. Hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects. Nutr Res. 1990;10:731-9.

Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, et al. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes. 1998;47:206-10.

Vijayakumar MV, Singh S, Chhipa RR, Bhat MK. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. British Journal of Pharmacology. 2005;146:41-8.

Amin R, Abdul-Ghani AS, Suleiman MS. Effect of Trigonella feonum graecum on intestinal absorption. Proc. of the 47th annual meeting of the American Diabetes Association (Indianapolis U.S.A.). Diabetes. 1987;36:211.

Raghuram TC, Sharma RD, Sivakumar B, Sahay BK. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phytother Res. 1994;8:83-6.

Diabetes control and complication trial research group. The effect of intensive treatment of diabetes on development and progression of long term complications in IDDM. N Engl J Med. 1993;329:977-86.

UK prospective diabetes study group: intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53.

Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats. Br J Nutr. 1993;69:277-87.

Varshney IP, Sharma SC. Saponins and sapogenins: part XXXII. Studies on Trigonella foenum-graecum Linn seeds. J Indian Chem Soc. 1966;43:564-7.

Sidhu GS, Oakenfull DG. A mechanism for the hypocholesterolaemic activity of saponins. Br J Nutr. 1986;55:643-9.

Mohan V, Balasubramanyam M. Fenugreek and insulin resistance. JAPI. 2001;49:1055-6.

Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Medi Rev. 2003;8(1):20-7.




How to Cite

Singh, A., Rai, J., & Mahajan, D. S. (2016). Comparative evaluation of glipizide and fenugreek (Trigonella foenum-graecum) seeds as monotherapy and combination therapy on glycaemic control and lipid profile in patients with type 2 diabetes mellitus. International Journal of Basic & Clinical Pharmacology, 5(3), 942–950.



Original Research Articles