A randomized, double-blind, placebo-controlled trial to evaluate the hypoglycemic efficacy of the mcIRBP-19-containing Momordica charantia L. fruit extracts in the type 2 diabetic subjects

  • Yi-Sun Yang Department of Internal Medicine, Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital, Taichung; and Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • Nian-Yi Wu Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan
  • Edy Kornelius Department of Internal Medicine, Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital, Taichung; and Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • Chien-Ning Huang Department of Internal Medicine, Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital, Taichung; and epartment of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • Nae-Cherng Yang Department of Nutrition, Chung Shan Medical University, Taichung; and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
Keywords: bitter gourd extracts, Momordica charantia insulin receptor binding peptide-19, type 2 diabetic subjects, fasting blood glucose, HbA1c


Background: The fruits of Momordica charantia L., also named as bitter gourd or bitter melon in popular, is a common tropical vegetable that is traditionally used to reduce blood glucose. A peptide derived from bitter gourd, Momordica charantia insulin receptor binding peptid-19 (mcIRBP-19), had been demonstrated to possess an insulin-like effect in vitro and in the animal studies. However, the benefit of the mcIRBP-19-containing bitter gourd extracts (mcIRBP-19-BGE) for lowering blood glucose levels in humans is unknown.

Objective: This aim of this study was to evaluate the hypoglycemic efficacy of mcIRBP-19-BGE in subjects with type 2 diabetes who had taken antidiabetic medications but failed to achieve the treatment goal. Whether glucose lowering efficacy of mcIRBP-19-BGE could be demonstrated when the antidiabetic medications were ineffective was also studied.

Design: Subjects were randomly assigned to two groups: mcIRBP-19-BGE treatment group (N = 20) and placebo group (N = 20), and were orally administered 600 mg/day investigational product or placebo for 3 months. Subjects whose hemoglobin A1c (HbA1c) continued declining before the trial initiation with the antidiabetic drugs were excluded from the subset analysis to further investigate the efficacy for those who failed to respond to the antidiabetic medications.

Results: The oral administration of mcIRBP-19-BGE decreased with a borderline significance at fasting blood glucose (FBG; P = 0.057) and HbA1c (P = 0.060). The subgroup analysis (N = 29) showed that mcIRBP-19-BGE had a significant effect on reducing FBG (from 172.5 ± 32.6 mg/dL to 159.4 ± 18.3 mg/dL, P = 0.041) and HbA1c (from 8.0 ± 0.7% to 7.5 ± 0.8%, P = 0.010).

Conclusion: All of these results demonstrate that mcIRBP-19-BGE possesses a hypoglycemic effect, and can have a significant reduction in FBG and HbA1c when the antidiabetic drugs are ineffective.


Download data is not yet available.


  1. International Diabetes Federation. IDF Diabetes Atlas. 8th ed. 2017. Available from: http://www.diabetesatlas.org/ [cited 28 April 2017].

  2. American Diabetes Association. 6. Glycemic targets: standards of medical care in diabetes – 2020. Diabetes Care 2020; 43(Suppl 1): S66–76. doi: 10.2337/dc20-S006

  3. Wallia A, Molitch ME. Insulin therapy for type 2 diabetes mellitus. JAMA 2014; 311: 2315–25. doi: 10.1001/jama.2014.5951

  4. Avilés-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999; 131: 182–8. doi: 10.7326/0003-4819-131-3-199908030-00004

  5. Nakar S, Yitzhaki G, Rosenberg R, Vinker S. Transition to insulin in Type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers. J Diabetes Complications 2007; 21: 220–6. doi: 10.1016/j.jdiacomp.2006.02.004

  6. Polonsky WH, Fisher L, Guzman S, Villa-Caballero L, Edelman SV. Psychological insulin resistance in patients with type 2 diabetes: the scope of the problem. Diabet Care 2005; 28: 2543–45. doi: 10.2337/diacare.28.10.2543

  7. Leung L, Birtwhistle R, Kotecha J, Hannah S, Cuthbertson S. Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): a mini review. Br J Nutr 2009; 102: 1703–8. doi: 10.1017/S0007114509992054

  8. Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, Sirigulsatien V, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol 2011; 134: 422–28. doi: 10.1016/j.jep.2010.12.045

  9. Singh J, Cumming E, Manoharan G, Kalasz H, Adeghate E. Medicinal chemistry of the anti-diabetic effects of Momordica Charantia: active constituents and modes of actions. Open Med Chem J 2011; 5(suppl2): 70–77. doi: 10.2174/1874104501105010070

  10. Joseph B, Jini D. Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pac J Trop Dis 2013; 3: 93–102. doi: 10.1016/S2222-1808(13)60052-3

  11. Tan MJ, Ye JM, Turner N, Hohnen-Behrens C, Ke CQ, Tang CP, et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol 2008; 15: 263–73. doi: 10.1016/j.chembiol.2008.01.013

  12. Iseli TJ, Turner N, Zeng XY, Cooney GJ, Kraegen EW, Yao S, et al. Activation of AMPK by bitter melon triterpenoids involves CaMKKβ. PLoS One 2013; 8: e62309. doi: 10.1371/journal.pone.0062309

  13. Khanna P, Jain SC, Panagariya A, Dixit VP. Hypoglycemic activity of polypeptide-p from a plant source. J Nat Prod 1981; 44: 648–55. doi: 10.1021/np50018a002

  14. Liu SX, Fu ZP, Mu RM, Hu ZB, Wang FJ, Wang XR. Expression and characterization of Momordica Chanrantia anti-hyperglycaemic peptide in Escherichia coli. Mol Biol Rep 2010; 37: 1781–6. doi: 10.1007/s11033-009-9609-0

  15. Rajasekhar MD, Badri KR, Vinay Kumar K, Babu KR, Fatima SS, Sampath Kumar MT, et al. Isolation and characterization of a novel antihyperglycemic protein from the fruits of Momordica cymbalaria. J Ethnopharmacol 2010; 128: 58–62. doi: 10.1016/j.jep.2009.12.025

  16. Lo HY, Ho TY, Lin C, Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem 2013; 61: 2461–8. doi: 10.1021/jf3042402

  17. Lo HY, Ho TY, Li CC, Chen JC, Liu JJ, Hsiang CY. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway. J Agric Food Chem 2014; 62: 8952–61. doi: 10.1021/jf5002099

  18. Lo HY, Li CC, Ho TY, Hsiang CY. Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein. Food Chem 2016; 204: 298–305. doi: 10.1016/j.foodchem.2016.02.135

  19. Lo HY, Li CC, Chen FY, Chen JC, Hsiang CY, Ho TY. Gastro-resistant insulin receptor-binding peptide from Momordica charantia improved the glucose tolerance in streptozotocin-induced diabetic mice via insulin receptor signaling pathway. J Agric Food Chem 2017; 65: 9266–74. doi: 10.1021/acs.jafc.7b03583

  20. Efird JT, Choi YM, Davies SW, Mehra S, Anderson EJ, Katunga LA. Potential for improved glycemic control with dietary Momordica charantia in patients with insulin resistance and pre-diabetes. Int J Environ Res Public Health 2014; 11: 2328–45. doi: 10.3390/ijerph110202328

  21. Dans AM, Villarruz MV, Jimeno CA, Javelosa MA, Chua J, Bautista R, et al. The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies. J. Clin Epidemiol 2007; 60: 554–9. doi: 10.1016/j.jclinepi.2006.07.009

  22. John AJ, Cherian R, Subhash HS, Cherian AM. Evaluation of the efficacy of bitter gourd (momordica charantia) as an oral hypoglycemic agent – a randomized controlled clinical trial. Indian J Physiol Pharmacol 2003; 47: 363–5.

  23. Zänker KS, Mang B, Wolters M, Hahn A. Personalized diabetes and cancer medicine: a rationale for anti-diabetic nutrition (Bitter Melon) in a supportive setting. Curr Cancer Ther Rev 2012; 8, 66–77. doi: 10.2174/157339412799462521

  24. Cheng AY, Fantus IG. Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ 2005; 172: 213–26. doi: 10.1503/cmaj.1031414

  25. Davis TM. Dipeptidyl peptidase-4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment. Diabetes Obes Metab 2014; 16: 891–9. doi: 10.1111/dom.12295

  26. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 2015; 75: 33–59. doi: 10.1016/10.1007/s40265-014-0337-y

  27. Shishikura K, Tanimoto K, Sakai S, Tanimoto Y, Terasaki J, Hanafusa T. Association between skeletal muscle mass and insulin secretion in patients with type 2 diabetes mellitus. Endocr J 2014; 61: 281–7. doi: 10.1507/endocrj.EJ13-0375

  28. Morais JA, Jacob KW, Chevalier S. Effects of aging and insulin resistant states on protein anabolic responses in older adults. Exp Gerontol 2018; 108: 262–8. doi: 10.1016/j.exger.2018.04.025

  29. Heymsfield SB, McManus C, Smith J, Stevens V, Nixon DW. Anthropometric measurement of muscle mass: revised equations for calculating bone-free arm muscle area. Am J Clin Nutr 1982; 36: 680–90. doi: 10.1093/ajcn/36.4.680

  30. Kwon HR, Han KA, Ahn HJ, Lee JH, Park GS, Min KW. The correlations between extremity circumferences with total and regional amounts of skeletal muscle and muscle strength in obese women with type 2 diabetes. Diabetes Metab J 2011; 35: 374–83. doi: 10.4093/dmj.2011.35.4.374

How to Cite
Yang Y.-S., Wu N.-Y., Kornelius E., Huang C.-N., & Yang N.-C. (2022). A randomized, double-blind, placebo-controlled trial to evaluate the hypoglycemic efficacy of the mcIRBP-19-containing <em>Momordica charantia L. </em&gt;fruit extracts in the type 2 diabetic subjects. Food & Nutrition Research, 66. https://doi.org/10.29219/fnr.v66.3685
Original Articles