Metformin, Empagliflozin With Sitagliptin vs Linagliptin in Type 2 Diabetes

February 27, 2026 updated by: Dr Khalil ur Rehman, Bahria University

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

This clinical trial aims to evaluate and compare the comparative efficacy and safety of Metformin-Empagliflozin-Sitagliptin vs. Metformin-Empagliflozin-Linagliptin in newly diagnosed Type 2 Diabetes Mellitus patients.

The study will involve 110 participants, aged 30-55, enrolled at the National Medical Centre, Karachi, Pakistan. The study involves two groups, subjects will receive the following treatments: 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. 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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

110

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Sindh
      • Karachi, Sindh, Pakistan, 75500
        • National Medical Center Karachi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Males and Females
  • Age 30-55 years
  • HbA1c = ≥ 8.5 <10 mmol/mol (ADA. 2025)
  • BMI >18.5- <29.9 (WHO Asian Criteria)
  • Treatment naïve patients
  • With / without dyslipidemia

Exclusion Criteria:

  • HbA1c >10 mmol/mol
  • BMI > 30 kg/m²
  • Pregnancy or lactation
  • Systemic diseases such as: hypertension, thyroid, liver, renal diseases etc.
  • Known allergy or intolerance to Metformin, Empagliflozin, Sitagliptin or Linagliptin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metformin + Empagliflozin (FDC)+ Sitagliptin
Metformin decrease hepatic production of glucose. Empagliflozin increase urinary glucose excretion. Sitagliptin increase glucose dependent insulin release.
Drug: Metformin+ Empagliflozin + Sitagliptin
Group A (Triple Therapy): Tab Metformin 1000mg + Tab Empagliflozin 12.5mg (FDC) + Tab Sitagliptin 50mg, orally, once daily for 90 days
Active Comparator: Metformin + Empagliflozin + Linagliptin
Metformin reduces hepatic glucose production. Empagliflozin raise excretion of urinary glucose. Sitagliptin increase glucose dependent insulin release.
Drug: Metformin + Empagliflozin + Linagliptin
Group B (Triple Therapy) Tab Metformin 1000mg + Tab Empagliflozin 12.5mg + Tab Linagliptin 2.5mg (FDC) orally, once daily, for 90 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome
Time Frame: 3 Months
Change in HbA1c levels in %
3 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome : changes in weight from baseline to 12 weeks (kg)
Time Frame: 12 weeks

the study will measure percentage change in weight from baseline to 12 weeks and proportion of participants achieving weight loss 1- 3 kg as national institute of health.

Time Frame: 12 weeks
12 weeks
Secondary Outcome: changes in BMI from baseline to 12 weeks (kg/m²).
Time Frame: 12 weeks
The study will measure percentage changes in BMI from baseline to 12 weeks and proportion of participants achieving required BMI
12 weeks
Secondary outcome: changes in lipid profile (TC, TG, HDL, LDL, VLDL) from baseline to 12 weeks (mg/dl)
Time Frame: 12 weeks
The study will measure the changes in lipid profiles level from baseline to 12 weeks to evaluate the efficacy of triple vs initial triple therapy
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
The study will measure the safety of Adverse Effects (nausea, vomiting, diarrhea, constipation, UTIs, flu like symptoms, headache, hypoglycemia, weight gain) from baseline to 12 weeks to evaluate the safety of triple vs initial triple therapy
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bahria University

Investigators

  • Principal Investigator: Khalil Ur Rehman, MBBS, Bahria University, Islamabad

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2026

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

December 18, 2025

First Submitted That Met QC Criteria

February 27, 2026

First Posted (Actual)

March 5, 2026

Study Record Updates

Last Update Posted (Actual)

March 5, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BUHS-IRB#179/25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes Mellitus

Clinical Trials on Metformin+ Empagliflozin + Sitagliptin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burundi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe