GlycaCare-II® tablets (522.5 mg) was manufactured and provided by Sami-Sabinsa Group Limited (erstwhile Sami Labs Limited), India. GlycaCare-II® contains the following ingredients:
Percentage (%) of Actives
Momordica charantia Extract
Pterocarpus Extract (Water-soluble)
Gymnema sylvestre Extract
25% gymnemic acids
Salacia reticulata extract
Eugenia jambolana extract
< 15% Tannins
Cinnamon (Cinnamomum cassia) bark, Gymnema (Gymnema sylvestre) leaves, deseeded (Momordica charantia) fruits, Dried fruits of Jamun(Eugenia jambolana), and Dried Salacia bark (Salacia reticulata) were powdered and extracted with methanolic water at refluxed condition. The extract was concentrated to remove methanol, dissolved in water, and spray dried. Dried Pterocarpus wood (Pterocarpus marsupium) was extracted with water.
Metformin (GLYCIRITE) tablets (500 mg) was manufactured by Tusker Pharma India Pvt. Ltd, India.
The present study was a prospective, randomized, double-blind, active-controlled clinical trial. Its primary objective was to evaluate the efficacy and safety of GlycaCare-II as monotherapy in Type 2 diabetes mellitus patients compared to metformin. Enrolled patients were initially segregated into prediabetic patients and newly diagnosed diabetic patients. The patients were randomly allocated into two treatment groups to prevent treatment bias. The patients and investigators were blinded to the treatment allocation. Out of 70 subjects screened, sixty-nine subjects enrolled in the study. All the enrolled patients were randomized to two treatment groups: Treatment 1: GlycaCare-II (522.5 mg) as active or Treatment 2: Metformin (500 mg) as the comparator. During the treatment phase, 29 prediabetic patients and 40 newly diagnosed diabetic patients with Type 2 Diabetes mellitus were randomized to receive either GlycaCare-II or metformin under each arm for a period of 120 days ± 3 days. Investigational Product (IP) was administered orally twice daily, morning and night, 20 min before food. All the participants signed informed consent before the beginning of the study after careful detailing regarding the purpose, procedure, and potential risks and benefits of the study.
Subjects within the age group of 30–65 years, having the ability to comply with the study protocol and willing to give written consent, were included in the study. Prediabetes was classified as per American diabetes association criteria HbA1c 5.7–6.4% and FBS between 100 mg/dL to 125 mg/dL. Newly diagnosed diabetes patients had an HbA1c value of 6.5–7.5% and FBS > 125 mg/dL . Pregnant and lactating women, patients with a history of acute or chronic illness, type I diabetes, hypo-, and hyperthyroidism were excluded from the study. Also, subjects with hyperlipidemia, history of severe hepatic dysfunction or renal dysfunction, uncontrolled pulmonary dysfunction, and poorly controlled hypertension were excluded from the study. Any patient did not use concomitant medications during the course of the trial.
Details of the subject’s disposition are presented in the consort flow chart (Fig. 1).
Ethics and informed consent
The study was planned at two centers; however, executed at only one site, Levin Diabetes Specialty Hospital, Madurai. The institutional ethics committee of both the hospitals approved it. However, the trial activity was terminated at the initial phase of the study at Pristine Hospital & Research Centre (P) Ltd due to non-compliance. The study was conducted on 69 subjects instead of the proposed 140 subjects. A protocol deviation pertaining to the change in the number of subjects was filed to the ethics committee, and the changes were duly updated in the Clinical Trial Registry of India (CTRI) with registration number CTRI/2018/02/012085 on February 22, 2018, retrospectively. Written Informed Consent was taken from all the subjects before enrolling in the study.
Data collection, compliance, and protocol deviation
This study was conducted in accordance with applicable regulations, GCP, and Standard Operating Procedures. Study monitor(s) from ClinWorld monitored the study process and data collection through periodical site visits. The monitor retrieved the CRFs (Case Report Form) upon satisfactory resolution of all the queries. Investigational Product (IP) compliance was maintained for both active tablets GlycaCare-II and comparator Glycirite tablets. IP compliances were assessed through CRF. There were no deviations observed regarding IP compliance, during the treatment.
Change in diabetic panel (Glycosylated hemoglobin (HbA1c), fasting blood sugar (FBS), and postprandial blood sugar (PBS)) is the primary endpoint. In case of secondary endpoints, adverse events and change in the biochemical parameters viz lipid profile (Total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL)), liver profile (aspartate transaminase (AST), alanine transaminase (ALT)) and renal profile (Serum creatinine) were performed. All routine clinical chemistry parameters were analyzed using Erba Chem 5® Plus V2 (ERBA Diagnostics Mannheim GmbH Mallaustrasse 69–73 68,219 Mannheim, Germany). Hematology was analyzed using 6 part cell analyzer, SYSMEX, XN-150, (Mumbai, 400 078, Maharashtra, India). HbA1c was analyzed using a D-10 analyzer, BIO-RAD Laboratories (Hercules, CA, USA).
Efficacy and safety parameters were assessed during the patients' visits to the site. Physical examination, demographics (height, weight, body mass index (BMI)), vital signs were assessed at each visit of the subjects. Clinical efficacy parameter HbA1c was assessed at the screening visit (day − 3) and final visit (day 120 ± 3). FBS and PBS were assessed at the screening visit (day − 3), visit 3 (day 20 ± 3), visit 4 (day 40 ± 3), visit 5 (day 60 ± 3), visit 6 (day 80 ± 3), visit 7 (day 100 ± 3) and final visit (day 120 ± 3). All the biochemical parameters viz thyroid profile (thyroid-stimulating hormone-TSH), lipid profile, liver profile, and renal profile were assessed at the screening visit (day − 3) and final visit (day 120 ± 3).
All patients in the study with relevant safety and efficacy data were considered for the analysis. Efficacy and safety endpoints were analyzed for the relevant study population. A descriptive analysis of demographic characteristics was performed. Mean, and the standard deviation was derived for numeric and categorical parameters. Vital signs at each visit were also analyzed descriptively. Both primary and secondary efficacy outcomes were analyzed descriptively.
For normally distributed data, parametric tests have been applied, and results on continuous measurements were presented as mean ± SD, and results on categorical measurements were presented in percentage (%). A statistical significance level of ≤ 5% was considered significant. Fasting and postprandial glucose levels have been evaluated using repeated-measures ANOVA. HbA1c levels at the screening visit (visit 1) and at the end of the treatment were evaluated using student's ―paired t-test.
As part of safety outcomes, adverse events, concomitant medications, and clinical laboratory data were assessed. Clinical laboratory outcomes were assessed descriptively. Mean and standard deviation were derived from the data. The p-value for each efficacy parameter and for individual laboratory parameters was calculated using the Wilcoxon test.