Efficacy and Safety of Low-Dose Semaglutide for Weight Loss and Cardiometabolic Improvement in Obese Pakistani Adults Without Type 2 Diabetes: A Single-Arm Open-Label Single-Center Trial
This prospective, open-label, single-arm, single-center interventional pilot trial aims to evaluate the efficacy and safety of low-dose semaglutide for weight loss and cardiometabolic improvement in obese Pakistani adults without type 2 diabetes mellitus. The study will be conducted at the Asian Institute of Medical Sciences (AIMS), Hyderabad, Sindh, Pakistan. A total of 60 obese adults aged 18 years or older with a body mass index (BMI) of 27.5 kg/m² or greater according to World Health Organization Asian cutoffs and without type 2 diabetes mellitus (fasting blood glucose \<126 mg/dL and HbA1c \<6.5%) will be enrolled. Eligible participants will receive once-weekly subcutaneous semaglutide following a standard dose titration schedule of 0.25 mg weekly for four weeks, 0.5 mg weekly for four weeks, and 1.0 mg weekly for the remaining 16 weeks, for a total treatment duration of 24 weeks. All participants will receive standardized lifestyle counseling, including a hypocaloric diet with a 500-750 kcal/day deficit and at least 150 minutes per week of moderate-intensity physical activity. The primary outcome is the percentage change in body weight from baseline to 24 weeks. Secondary outcomes include changes in body mass index, waist circumference, systolic and diastolic blood pressure, lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides), liver enzymes (alanine aminotransferase and aspartate aminotransferase), and quality of life. Safety will be assessed through continuous monitoring of adverse events and adverse drug reactions with causality assessment using the Naranjo Adverse Drug Reaction Probability Scale. Clinical and laboratory assessments will be conducted at baseline, 12 weeks, and 24 weeks. Data will be analyzed using descriptive and inferential statistics, including paired t-tests or non-parametric equivalents and repeated measures analysis, with a significance level of p \< 0.05. The study will be conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki, with approval from the AIMS Institutional Review Board and written informed consent obtained from all participants. The trial aims to generate locally relevant clinical evidence on the effectiveness and safety of low-dose semaglutide for obesity management in non-diabetic Pakistani adults.
• Adults aged 18 years or older.
• Body mass index (BMI ≥ 27.5 kg/m²) according to WHO Asian cut-offs.
• No diagnosis of type 2 diabetes mellitus, confirmed by:
⁃ Fasting blood glucose \< 126 mg/dL, and HbA1c \< 6.5% within three months prior to enrollment.
• Willingness and ability to provide written informed consent.
• Willingness to comply with study procedures, including weekly injections and lifestyle counseling.