Metformin, Empagliflozin With Sitagliptin vs Linagliptin in Type 2 Diabetes

To evaluate and compare The Comparative Efficacy and Safety of Metformin-Empagliflozin-Sitagliptin vs. Metformin-Empagliflozin-Linagliptin as Initial Triple Therapy in Type 2 Diabetes Mellitus.

Newly diagnosed males and females with type 2 diabetes mellitus having age between 30 to 55 years presenting in diabetic OPD of National Medical Centre Karachi Pakistan.

This clinical trial will be conducted on 94+16=110 newly diagnosed cases of Type 2 Diabetes Mellitus in the National Medical Centre after approval from IRB of Bahria University Health Sciences Campus Karachi. Patients will be enrolled after taking written informed consent. The study design is Randomized open label, parallel arms, clinical trial. They will be randomized into two groups using a sealed enveloped method and a non-probability consecutive sampling technique. Total sample size is 94 with 47 patients in each group. However, investigator will work on 110 subjects 55 in each group. Group A will receive Tab Metformin 1000mg + Tab Empagliflozin 12.5mg (FDC) + Tab Sitagliptin 50mg, whereas Group B will receive Tab Metformin 1000mg + Tab Empagliflozin 12.5mg + Tab Linagliptin 2.5mg (FDC) per orally, once daily, for 90 days.

Complete safety profile parameters and analysis, will be done at baseline, week 6 and week 12 in addition to the following:

Baseline= Anthropometric measurements (weight, height, BMI, waist, hip circumference, waist to hip ratio, neck circumference), and all lab investigations (Glycemic profile including Fasting Blood Sugar, Random Blood Sugar, HbA1c), (Lipid profile TC mg/dl, TG mg/dl, HDL mg/dl, LDL mg/dl, VLDL mg/dl), safety profile ( Blood (CBC), renal (Serum urea, Serum creatinine, Glomerular Filtration Rate, Urine for Microalbumin), hepatic ( Alanine Transaminase, Aspartate Aminotransferase), and Cardiac (Triglycerides, High Density Lipoprotein, Uric Acid).

FBS \& RBS on weekly basis. Day 45= Anthropometric measurements (weight, height, BMI, waist, hip circumference, waist to hip ratio, neck circumference), and lab investigations (only FBS or RBS) will be done. Adverse events (hypoglycemia, nausea, vomiting, diarrhea, constipation, headache, weight gain, urinary tract infection, flu-like symptoms and any others).

Day 90= Anthropometric measurements (weight, height, BMI, waist, hip circumference, waist to hip ratio, neck circumference), and all lab investigations (Glycemic profile including Fasting Blood Sugar, Random Blood Sugar, HbA1c), (Lipid profile TC mg/dl, TG mg/dl, HDL mg/dl, LDL mg/dl, VLDL mg/dl), safety profile ( Blood (CBC), renal (Serum urea, Serum creatinine, Glomerular Filtration Rate, Urine for Microalbumin), hepatic ( Alanine Transaminase, Aspartate Aminotransferase), and Cardiac (Triglycerides, High Density Lipoprotein, Uric Acid). Adverse events (hypoglycemia, nausea, vomiting, diarrhea, constipation, headache, weight gain, urinary tract infection, flu-like symptoms and any others).

Expected outcomes of the study will be :

1. Clinical Efficacy Evaluation:

Improvement is expected regarding anthropometric measures such as weight, BMI, hip circumference, and waist circumference, they will be measured to track changes in body composition.

Assessment of glycemic indicators, including glycated hemoglobin (HbA1c), random blood sugar (RBS), and fasting blood sugar (FBS), in order to gauge progress in glucose regulation.

To detect any positive changes in lipid level, lipid profile parameters such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides will be done and analyzed. 2. Comparison of Clinical Efficacy:

Evaluation of the effects on anthropometric, glycemic, and lipid profile parameters of of the effectiveness of two combination treatments (Metformin + Empagliflozin + Sitagliptin vs. Metformin + Empagliflozin + Linagliptin).

Determination of which drug combination regimen will be better based on the results observed. 3. Assessment of adverse Effects:

Monitoring and recording of side effects , such as genitourinary infections, gastrointestinal symptoms, and other reported side effects, related to each drug combination regimen. A comparison of various treatment group's adverse effect rates and severity. 4. Safety Evaluation:

To ensure the safety of the combination drug regimens, safety profiles will be evaluated using blood parameters, renal function tests, hepatic function tests, and cardiac parameters.

For point #2,3 \& 4 to come up with a best drug combination regimen for our Type2 diabetics.

• Secondary Outcome : changes in weight from baseline to 12 weeks (kg) [Time frame: 12 weeks]
• Secondary Outcome: changes in BMI from baseline to 12 weeks (kg/m²). [Time frame: 12 weeks]
• Secondary outcome: changes in lipid profile (TC, TG, HDL, LDL, VLDL) from baseline to 12 weeks (mg/dl) [Time frame: 12 weeks]
• Secondary Outcome: To measure safety of Adverse Effects (nausea, vomiting, diarrhea, constipation, UTIs, flu like symptoms, headache, hypoglycemia, weight gain) from baseline to 12 weeks [Time frame: 12 weeks]