Glimepiride, Empagliflozin, and Sitagliptin With Metformin for Type 2 Diabetes

This clinical trial aims to evaluate and compare the clinical efficacy and safety of Glimepiride, Empagliflozin, and Sitagliptin with Metformin in newly diagnosed Type 2 Diabetes Mellitus patients.

The study will involve 172 participants, aged 30-55, enrolled at the National Medical Centre, Karachi, Pakistan. The study involves four groups, subjects will receive following treatment: Group A will receive Tab Metforrmin 500mg + Tab Glimepiride 2mg (FDC) , Group B Tab Metforrmin 500mg + Tab Empagliflozin 12.5mg (FDC), Group C Tab Metforrmin 500mg + Tab Sitagliptin 50mg (FDC) and Group D Tab Metformin 500mg + Tab Empagliflozin 12.5mg (FDC) + Tab Sitagliptin 50mg per orally, once daily for 90 days. Safety and efficacy will be assessed through anthropometric measurements and lab investigations at baseline, 6 weeks, and 12 weeks, with weekly monitoring of blood sugar levels. The total duration of the study will be 6 months, with a 3-month individual treatment period.

To evaluate and compare the clinical efficacy and safety of Glimepiride, Empagliflozin and Sitagliptin with Metformin in Type 2 Diabetes Mellitus: A double and triple drug therapy.

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

This clinical trial will be conducted on 135±37=172 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 four groups using a sealed envelop method and a non-probability consecutive sampling technique. Total sample size is 135 with 33 patients in each group. However, investigator will work on 172 subjects 43 in each group. Group A will receive fixed drug combination (FDC) of Tab Metforrmin 500mg + Tab Glimepiride 2mg, Group B Tab Metforrmin 500mg + Tab Empagliflozin 12.5mg, Group C Tab Metforrmin 500mg + Tab Sitagliptin 50mg and Group D Tab Metformin 500mg + Tab Empagliflozin 12.5mg (FDC) + Tab Sitagliptin 50mg 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 investigation (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, AspartateAminotransferase) 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 (nausea, vomiting, diarrhea, hypoglycemia, weight gain, constipation, headache, 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), all Lab investigation (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, AspartateAminotransferase) and cardiac (Triglycerides, High Density Lipoprotein, Uric Acid). Adverse events ( nausea, vomiting, hypoglycemia, weight gain, diarrhea, constipation, headache, urinary tract infection, flu like symptoms and any others)

Individual study period will be 3 months. Total duration of study will be 6 months.

Expected outcome 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 levels, 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 the effectiveness of four combination treatments (Metformin + Glimepiride, Metformin +Empagliflozin, Metformin + Sitagliptin, and Metformin + Sitagliptin + Empagliflozin). Determination of which drug combination regimen will be better based on the results observed.
3. Assesment 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 the various treatment groups' 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.

Eligibility Criteria:
Inclusion Criteria:

* Males and females
* Age 30-55yrs
* HbA1c = ≥ 8.5 \<10 mmol/mol (ADA. 2018)
* BMI \>18.5- \<29.9 (WHO Asian Criteria)
* Treatment naïve patients
* With / without dyslipidemia.

Exclusion Criteria:

* HbA1c \>10 mmol/mol
* BMI \> 30
* Pregnancy or lactation
* Systemic diseases such as: hypertension, thyroid, liver, renal diseases etc.
* Known allergy or intolerance to Metformin, Glimepiride, Sitagliptin or Empagliflozin.