Comparison of the effects of pioglitazone and linagliptin on glycemic control, lipid profile, and hs-CRP in patients with type 2 diabetes mellitus under treatment with metformin

Objective: The aim of this study is to compare the effects of pioglitazone and linagliptin on glycemic control, lipid profile, and hs-CRP in patients with type 2 diabetes mellitus under treatment with metformin.

Study design: Randomized double-blind trial. Patients will be assigned into two groups to receive pioglitazone (n=30) or linagliptin (n=30).

Among patients with T2DM referred to Beheshti Clinic affiliated to Kashan University of Medical Sciences, 60 patients will be selected according to inclusion and exclusion criteria. Participants, investigators or the assessors of the outcomes are unaware of the study groups. Drugs are similar in shape and size. Fasting blood samples will be taken at baseline and 3 months after the intervention. Intervention period: 3 months.

Inclusion criteria: Patients diagnosed with type 2 diabetes, aged 30-50 years old. FBS ≥140. people under treatment with metformin for at least 3 months. Exclusion criteria: Secondary diabetes due to cushing syndrome, acromegaly and other diseases, systemic inflammatory diseases such as rheumatoid arthritis, IBD, vasculitis, etc, renal or liver or heart failure, malignancy, under insulin therapy, pregnancy, unwillingness to cooperate.

Intervention group1: 30 mg pioglitazone (Osveh pharmaceutical company, Tehran, Iran) daily, for 3 months orally. Intervention group2: 5 mg linagliptin (Alhavi pharmaceutical company, Tehran, Iran) daily, for 3 months orally.

Outcomes: fasting blood glucose (primary outcome) and lipid profile, serum hs-CRP, anthropometric indices, and HbA1c (secondary outcomes) will be quantified at study baseline and end-of-trial.

Patients will be randomly assigned into two groups. A randomization list will be generated from 1 to 60 by a random number generator (https://stattrek.com/statistics/random-number-generator.aspx) and patients were randomly assigned into each intervention group by their numbers. The block randomization technique (including AABB, BBAA, ABAB BABA, ABBA, BAAB) with 1:1 ratio will be used to achieve balanced group sizes. Drugs and placebos are in the same packaging at the Pharmaceutical company. Only the code is written on the packages. Patients and researchers do not know the type of drug and after analyzing the data, packet codes are decoded.

Randomization and allocation will be concealed from the researchers and participants until the final analyses are completed. Another person at the Beheshti clinic, who is not involved in the trial and not aware of random sequences, will be assigned the participants to the numbered bottles of drugs.