- Diabetes mellitus is the new epidemic.
- The prevalence of diabetes for all age groups worldwide was estimated to be 2.8% in 2000, and to rise to 4.4% by the year 2030.1 According to local data, the prevalence rate of diabetes in the Philippines is 4.6%, based on fasting blood sugar (FBS) > 125 mg/dL or a previous history of diabetes.2
- There are currently many classes of pharmacological agents for type 2 diabetes mellitus, however, these drugs have also shown adverse effects, including hypoglycemia, lactic acidosis, and diarrhea.5
- Studies of functional food components with blood glucose-controlling effects are in progress, and many useful components have been discovered in plants.6-7
- Momordica charantia, is a well-known plant for its glucose-lowering properties.15,16. The mechanism of action of the hypoglycemic effect brought about by Momordica charantia has been variedly described.
- The leaves of Momordica charantia, particularly of the Makiling variety, produced the most consistent hypoglycemic properties with acceptable safety profiles compared to other parts of the plant.18-19. It has undergone several clinical trials.18, 20, 21
- The joint position statement of the Philippine Society of Endocrinology and Metabolism, Philippine Diabetes Association, Institute for Studies on Diabetes Foundation, and Philippine Center for Diabetes Education Foundation still does not consider ampalaya-derived products as part of the standard care for diabetes in the absence of more research data.
- The pharmacodynamics of the Momordica charantia tablets has not been determined, especially as it relates to blood glucose and insulin levels at different doses.
- It is the purpose of this study to provide physicians with significant data on the comparative efficacy of Momordica charantia tablets and placebo as glucose lowering agents among subjects, emphasizing its effect on blood glucose and insulin levels.
- To compare the effect of Momordica charantia tablets and placebo on insulin secretion and glucose excursions among type 2 diabetic patients using different doses.
- To demonstrate the mechanism of action of Momordica charantia by determining its effect in insulin levels.
- To determine the time of peak effect and onset of efficacy of Momordica charantia tablets versus placebo using different doses of 60 mg/kg/ day, 80 mg/kg/day and 100 mg/kg/day among patients with type 2 diabetes mellitus during the postprandial state.
- Double-blind, placebo-controlled, randomized trial conducted in the Philippine General Hospital, from June to December 2008.
- Study population: Subjects from the outpatient clinics of the University of the Philippines-Philippine General Hospital.
- Type 2 diabetes mellitus based on the American Diabetes Association (ADA) Criteria for Diabetes Mellitus, 2007 (APPENDIX B)
- Newly diagnosed diabetes mellitus AND is drug naïve OR is NOT on anti-diabetic agents for the past 3 months
- 3. Glycemic criteria: Glycosylated hemoglobin (HbA1c) ≥ 6.5% and ≤ 9.0% and fasting blood glucose of ≥126 mg/dL but ≤ 205 mg/dL
- 4. Patient is ≥ 21 years old but ≤ 65 years old
- Unstable co-morbidities
- Significant acute illness in the previous 2 weeks before the start of the study
- History of diabetic emergency
- History of corticosteroid use, herbal medications or any other drugs that may affect glucose metabolism within the preceding 6 months
- Hypersensitivity to the drug
- Presence of conditions affecting compliance, e.g., drug or alcohol abuse or psychiatric illness
- Recipient of another investigational drug during and preceding 6 months
- Unwillingness to participate in the study
Materials and Methods
1. Data collection
a. Determination of clinical data.
- Volunteers were asked to sign a written consent after explaining the objectives and procedures involved in the study and then were then interviewed upon entry to the study.
b. Physical examination and determination of baseline measurements.
- Subjects underwent a standard physical examination with waist-to-hip ratio and calculation of Body mass index (BMI).
c. Screening laboratory tests.
- Blood was extracted for baseline serum HbA1c, FBS, blood urea nitrogen (BUN), creatinine, AST, ALT, complete blood count (CBC) levels.
- Random allocation was done using a computer-generated sequence of random numbers (Stata® version 6.0). Medications were prepared by a third party with placebo tablets matched in appearance and packaged in unpackaged blisters.
3. Study Proper
a. Test Drug
- Momordica charantia (Amargozin) 500 mg/tab, obtained from a local licensed pharmacy in Manila.
- Dummy placebo tablets formulated by an industrial pharmacy to simulate the 500 mg Momordica charantia tablets.
b. Study Protocol
- Volunteers were randomly allocated to one of four groups according to single oral doses of Momordica charantia tablets at 60, 80, or 100 mg/kg/day and placebo.
- After 8 hours of fasting at time 0, they were given either one of the three doses of Momordica charantia or placebo after which they were then given a standard meal consisting of 56.6 g carbohydrate, 19.5 g protein, 11.5 g fat and 395 kcal.
c. Study evaluations
- Plasma glucose and insulin concentrations were measured at multiple time-doses from pre-dose to 4 hours post-dose: namely 0 minute, 15 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours after the given dose.
- Fasting blood sugar and blood insulin levels were determined using standardized kits.
d. Discontinuation of testing
- Study therapy was immediately discontinued for the following reasons:
- Withdrawal of informed consent.
- The primary outcome was the change in glucose and insulin level 4 hours after administration of treatment.
- Adverse events were monitored and recorded.
- The end points were summarized using proportions and analyzed using one way and repeated measures ANOVA and Kruskal Wallis tests.
- Bonferroni and Rank sum pairwise comparison tests were also used for the statistical analyses.
- The main ethical issue for this study was the possible adverse effects of the intervention of Momordica charantia tablets.
- The following adverse effects were noted: gastric pain, nausea, vomiting, diarrhea, dyspnea, headache, dizziness, and rashes.
- Any adverse event that was incurred during the study period, was addressed immediately and was compensated by the investigators.
- 40 Filipino healthy Type 2 diabetic patients, 18 males and 22 females with mean age of 56.6 ± 1.28 years and majority being overweight or obese with mean body weight of 62.98 ± 1.92 kg, BMI of 25.6 ± 0.23 kg/m2 and WHR of 0.95 ± 0.01, respectively.
- Baseline HbA1c, FBS and insulin levels: 7.78 ± 0.27 %, 172.2 ± 1.8 mg/dl, and 23.51 ± 1.52 uIU/ml.
- All 40 participants completed the study.
- No clinically meaningful changes in vital signs were reported during the study or at the end-of-study evaluations.
- No reports of adverse events.
- The placebo and ampalaya tablets were generally acceptable and well tolerated by the subjects.
- All active drug treatments increased plasma insulin levels in response to a standardized breakfast relative to placebo.
- During the initial 15-minute post meal interval, 100 mg/kg/day dose of Momordica charantia tablets significantly produced a more increased induction of insulin secretion than 80 mg/ kg/day, 60 mg/kg/day and placebo (p≤0.10) with mean rates of rise in insulin secretion of 48.49 ± 9.26, 40.3 ± 6.28, 37.29 ± 6.47, and 38.81 ± 16.76 uIU/ml, respectively.
- Mean plasma insulin concentrations peaked at 30 minutes post dose for both the placebo and the three treatment groups and after this peak concentration, mean plasma insulin decreased in all groups and was similar to placebo by 1-hour post dose.
- The rapid effects of the 100 mg/kg/day dose of ampalaya tablets resulted in significantly higher average plasma insulin over the early 0- to 0.25-h post dose intervals (36.42 ± 15.40 uIU/ml) compared with ampalaya doses of 80 mg/kg/day (32.70 ± 9.96 uIU/ml), 60 mg/kg/day (29.87 ± 9.95uIU/ml) and placebo (30.46 ± 16.48 uIU/ml).
- The 100 mg/kg/day group has the lowest average plasma glucose levels after 15 minutes.
- Compared with ampalaya tablets at 80 mg/kg/day, 60 mg/kg/day, and placebo, Momordica charantia at 100 mg/kg/day produced lower average plasma glucose concentrations (188.48 ± 35.97 mg/dl) over the 0- to 4-hour post dose interval.
- This study involving 40 adult type 2 diabetics, Momordica charantia tablet given as a single dose using the 100 mg/kg/day dose (12 tablets of 500 mg/ tab), showed an incremental dose effect and provided a more rapid (15 minutes) and shorter-lived (30 minutes) stimulation of insulin secretion than placebo, resulting in lower meal-related glucose excursions.
- This herbal product has the potential to be used for reducing post-meal hyperglycemia.
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