Comparison of the effect of Empagliflozin and Sitaglipin, as add on to metformin on Fetuin-A serum level and insulin resistance in patient with type 2 diabetes

Comparison of the effect of Empagliflozin and Sitaglipin, as add on to metformin on Fetuin-A serum level and insulin resistance in patient with type 2 diabetes

A single-blind, randomized, parallel-group clinical trial of 74 patients using stratified permuted block randomization.

A single-blind randomized trial on 74 type 2 diabetes patients at Tohid Diabetes Clinic in Sanandaj. Patients will be randomly allocated (using permuted block stratified randomization) to either empagliflozin + metformin or sitagliptin + metformin groups. Outcome assessors, statistical analysts, and the safety committee will be blinded

Inclusion Criteria: Iranians with T2DM (6mo-10yrs), BMI more than 25, no recent acute illness, on metformin with HbA1c 7.5-8.5%. Exclusion Criteria: Severe diabetes complications, cognitive disorders, BP more than or equal to 180/110, hemolytic anemia, hemoglobinopathies, or recent diabetes medication changes.

This single-blind clinical trial compares the efficacy of two active treatment regimens in patients with type 2 diabetes. In the first group, patients will receive a fixed dose of empagliflozin 10 mg daily along with metformin at an adjusted dose between 1000-2000 mg daily. In the second group, patients will receive sitagliptin at a renal function-adjusted dose (100 mg daily for eGFR≥50, 50 mg for eGFR 30-49, and 25 mg for eGFR<30) along with metformin following the same dosing protocol as the first group. The treatment protocol includes gradual initiation of metformin starting from 500 mg with weekly dose escalation based on patient tolerance, and metformin will be discontinued in cases of reduced kidney function (eGFR<30).

Primary: -Serum fetuin-A level, -Insulin resistance. Secondary: -Fasting blood glucose, -Hemoglobin A1c, -lipid profile, -BMI.

Method of randomization: Stratified permuted block randomization (block sizes: 4, 6) to ensure balanced allocation. Unit of randomization: Individual participants. Randomization strata: age (less than 50 years versus age greater than or equal to 50 years), sex, and duration of diabetes (greater than or equal to 5 years versus less than 5 years). Randomization tool: Computer-generated random sequences (statistical software), with separate sequences per stratum. Random sequence generation: Software-produced sequences ensured unpredictability within blocks. Allocation concealment: Maintained via an independent researcher using sequentially numbered, opaque envelopes or a secure electronic system.

In this study, three main groups including outcome assessors (who measure outcomes without knowledge of group allocation), data analysts (who do not have access to grouping information), and the Data and Safety Monitoring Board (who only access allocation information when necessary) were kept blinded to participant allocation to prevent bias. Evaluations were based on coded data and analyses were performed independently.

The fully anonymized participant data will be shareable upon reasonable request after study completion. The shareable materials include the following: The dataset will include non-identifiable clinical parameters such as HbA1c, blood pressure, and lipid profiles. It should be noted that all personally identifiable information including names, IDs, and contact details will be permanently removed. In the documentation section, the study protocol in both Farsi and English, data collection forms as blank templates, and educational materials including video scripts and booklet content will be made available. The access conditions for this data are such that six months after study publication, the data will become accessible. Requesters must comply with the following requirements: a) Submission of a formal research proposal b) Signing a data use agreement that prohibits re-identification c) Proper source attribution in their publications

Data will be available 6 months post-publication.

The study data and documents will be accessible to both of the following groups: A) Academic researchers: University faculty members, Research institute scientists, Graduate students (with supervisor approval). B) Industry/clinical professionals: Practicing physicians and nurses, Pharmaceutical/medical device specialists, Research & Develpment specialists in health-related companies.

Access to de-identified data and study documents is subject to the following requirements: a) General Conditions: Submission of formal request including research objectives, analysis plan and timeline, Approval by the ethics committee of requester's institution, Signed limited data use agreement. b) Analytical Restrictions: Any statistical analysis is permitted provided it doesn't enable indirect identification, Subgroup comparisons require minimum 10 cases per group, Machine learning applications need separate approval. c) Usage Permissions: Permitted for academic research and therapeutic protocol development, Commercial use requires separate licensing agreement, Educational materials may be redistributed with proper attribution. d) Oversight Mechanisms: Mandatory progress reports every 6 months, Periodic audits by independent data monitor, Data deletion commitment after project completion.

Interested parties may submit their requests for study data and documentation to the following email address: golnaz.azami64@gmail.com

Request Procedure: Formal Request Submission: Complete request form (if applicable), Email to golnaz.azami64@gmail.com with clear subject. Attach: -Research proposal, -Ethics approval, -Affiliation documents. *Initial Review (3-5 business days): -Document completeness check, -Research objectives alignment assessment, *Technical Evaluation (7-10 business days): -Analysis plan review by technical team, -Access level determination, -De-identified data preparation. *Agreement Finalization (5-7 business days): -NDA signing, -Usage terms confirmation. -Cost determination (if applicable). *Data Delivery (2-3 business days post-agreement): -Secure platform transfer, -User guide provision, -Analysis restrictions specification, Total Processing Time: 15-25 business days (depending on request complexity).