What is the difference in the treatment efficacy of two different dose regimes of LG against placebo as add-on therapy to metformin in uncomplicated type 2 diabetes mellitus?

Setting: The study will be conducted at the Colombo Municipal clinic (CMC) in Slave Island, Sri Lanka. Patients who have been diagnosed with type 2 diabetes mellitus (T2DM) who fulfill both the inclusion and exclusion criteria will be selected for the study. The patients that are excluded will receive standard care provided by the CMC clinic.

Enrollment: An advertisement about the details of the study and contact number of PI will be displayed in all three languages (Sinhala/English/Tamil) at the CMC clinic at Slave Island. Interested participants will contact PI and they will be approached by a trained medically qualified research assistant who has completed GCP training for the initial screening using inclusion and exclusion criteria.

Randomization: Simple randomization method using computer-generated random numbers. The patients will be randomized in a 1:1:1 ratio.

Blinding: Neither participants, nor investigators, nor data collectors nor the study team nor data analysts will be aware of treatment assignments prior to the final breaking of codes of database. The codes of database will be opened after completion of data analysis and conclusion of the study.

Intervention: The LG and placebo tablets will be manufactured to have identical shape and size and will be film coated to give the same appearance. These 3 types of identical looking tablets will be packed into food grade white HDPE (High Density Polyethylene) plastic bottles identical in appearance. They will be numbered from 1 to 180 by a senior R&D Scientist (Pharmacist) at Link Natural Products (Pvt.) Ltd. according to the list of computer-generated random numbers. The label of each bottle will indicate only the patient’s random number and the directions for taking the tablets. Each bottle contains medication/ placebo required for 30 days.

Dosage form of LG and placebo is a tablet. High dose LG group will administer two tablets of LG three times a day and low dose LG group will administer one tablet three times a day. Half of the participants in the placebo group will receive two placebo tablets three times a day and the remaining half will receive one placebo tablets three times a day. Three groups (LG High dose, LG low dose and placebo) will receive Metformin 500 mg two times a day as the standard treatment for the participants that qualify with below mentioned inclusion criteria. All drugs will administer immediately after the meals. The duration of the study is 3 months.

LG tablet comprises of seven herbal ingredients namely stem of Salacia reticulata Wight, corm of Musa paradisiaca L., whole plant of Sida rhombifolia L., whole plant of Tribulus terrestris L., fruit of Phyllanthus emblica L., heartwood of Santalum album L. and whole plant of Coccinia grandis (L.) Voigt.

The placebo tablet comprises, microcrystalline cellulose BP., maize starch BP., sodium starch glycolate BP., carboxymethyl cellulose BP., Aerosil 200 Pharma., and magnesium stearate BP [All excipients in the investigational medicine other than the active ingredient is included].

• Males and females age 18–70 years • Diagnosed with type-2 diabetes mellitus during the last 5 years • Currently only taking metformin 500 mg twice a day for not more than 3 months • HbA1c 6.5–8.0% and FBS 126–200 mg/dl (Diabetes is defined as the presence of FPG more than 126mg/dL (7.0 mmol/L))

• Patients with an allergy to ingredients of LG • Alcohol consumption > 20 g/day
• Patients using insulin therapy
• Use of any herbal medications or herbal supplements, if any, were not discontinued at least 4 weeks prior to entry into the study. • Patients with raised baseline serum creatinine level (>1.5 mg/dl in men or > 1.2 mg/dl in women) • Lactation, pregnancy • Patients with diagnosed alcoholic liver disease (ALD), cirrhosis or abnormal baseline liver function tests (AST or ALT > 40 IU/ L) • Patients with malignancy • Patients with unrelated chronic illness • Diabetic retinopathy or neuropathy • Patients with cardiac, liver or respiratory failure • Any condition that, in the opinion of the clinician, would contraindicate the patient’s participation