Low-Dose Semaglutide for Weight Loss in Obese Non-Diabetic Pakistani Adults

Официальное название

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

Обзор

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.

Подробное описание

Obesity is a growing public health concern worldwide and is increasingly prevalent in Pakistan, contributing significantly to cardiovascular disease, metabolic syndrome, non-alcoholic fatty liver disease, hypertension, dyslipidemia, and reduced quality of life. Despite the rising burden of obesity in South Asian populations, access to evidence-based pharmacological treatment remains limited, and locally generated clinical data on anti-obesity medications in non-diabetic individuals are scarce. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated significant weight reduction and cardiometabolic benefits in multiple international clinical trials; however, most available evidence comes from Western populations and higher-dose formulations. In Pakistan, locally available lower-dose semaglutide formulations are increasingly being used in clinical practice, but their real-world effectiveness and safety in non-diabetic obese adults have not been systematically evaluated. This study aims to generate locally relevant clinical evidence to support the safe and effective use of semaglutide for obesity management in the Pakistani population.

This prospective, open-label, single-arm, single-center pilot interventional trial will be conducted at the Asian Institute of Medical Sciences (AIMS), Hyderabad, Sindh, Pakistan. The study will enroll 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, confirmed by fasting blood glucose less than 126 mg/dL and HbA1c less than 6.5% within three months prior to enrollment. Participants with a history of pancreatitis, medullary thyroid carcinoma, multiple endocrine neoplasia type 2, pregnancy or lactation, severe renal or hepatic impairment, current use of other anti-obesity medications, or known hypersensitivity to semaglutide will be excluded to ensure participant safety and minimize confounding factors.

Eligible participants will receive once-weekly subcutaneous low-dose semaglutide following a standardized dose titration schedule consisting of 0.25 mg weekly for the first four weeks, 0.5 mg weekly for the next four weeks, and 1.0 mg weekly for the remaining 16 weeks, for a total treatment duration of 24 weeks (six months). The medication will be administered under medical supervision, and participants will be educated on proper injection technique and adherence to the treatment regimen. In addition to pharmacological treatment, all participants will receive standardized lifestyle counseling, including a hypocaloric diet with a daily caloric deficit of 500-750 kcal and at least 150 minutes of moderate-intensity physical activity per week, in accordance with international obesity management guidelines.

The primary objective of the study is to evaluate the percentage change in body weight from baseline to 24 weeks following low-dose semaglutide treatment. Secondary objectives include evaluating changes in body mass index, waist circumference, systolic and diastolic blood pressure, lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides), liver enzymes (alanine aminotransferase and aspartate aminotransferase), and quality of life over the study period. Safety and tolerability 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 to evaluate treatment response and safety outcomes.

Data will be collected using standardized case report forms and securely stored in a password-protected database. Statistical analysis will be performed using IBM SPSS Statistics software. Descriptive statistics will summarize baseline demographic and clinical characteristics. Continuous variables will be expressed as mean with standard deviation or median with interquartile range, and categorical variables will be expressed as frequencies and percentages. Changes in primary and secondary outcomes from baseline to follow-up visits will be analyzed using paired t-tests or non-parametric equivalents depending on data distribution, and repeated measures analysis will be used to assess trends across time points. A p-value of less than 0.05 will be considered statistically significant. As a pilot trial, the sample size of 60 participants is intended to assess feasibility, estimate treatment effect, and generate preliminary data for future multicenter randomized controlled trials.

The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Ethical approval will be obtained from the Institutional Review Board of the Asian Institute of Medical Sciences prior to study initiation. Written informed consent will be obtained from all participants before enrollment, and participant confidentiality will be maintained through de-identification and secure data handling. The results of this study are expected to provide important real-world clinical evidence on the effectiveness and safety of low-dose semaglutide for obesity management in non-diabetic Pakistani adults and support future larger-scale clinical research in the region.

Вмешательства

• Препарат Locally available low-dose semaglutide (0.25 mg, 0.5 mg, 1 mg)
  Once-weekly subcutaneous injections following a titration schedule (0.25 mg for 4 weeks, 0.5 mg for 4 weeks, 1.0 mg for remaining 16 weeks) for a total of 24 weeks.

Первичные конечные точки

• Percentage Change in Body Weight [Срок оценки: Baseline to 24 weeks]

Вторичные конечные точки (5)

• Change in Body Mass Index (BMI) [Срок оценки: Baseline, 12 weeks, and 24 weeks]
• Change in Waist Circumference [Срок оценки: Baseline, 12 weeks, and 24 weeks]
• Change in Lipid Profile [Срок оценки: Baseline, 12 weeks, and 24 weeks]
• Change in Liver Enzymes [Срок оценки: Baseline, 12 weeks, and 24 weeks]
• Safety and Adverse Drug Reactions [Срок оценки: Continous throughout 24 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• History of pancreatitis.
• History or presence of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2).
• Pregnant or lactating women.
• Severe renal impairment (eGFR < 30 mL/min/1.73 m²) or hepatic impairment (ALT or AST > 3× upper limit of normal).
• Current use of other anti-obesity medications.
• Known hypersensitivity to semaglutide or any component of the formulation.
• Any condition that, in the investigator's opinion, would interfere with participation, adherence, or safety in the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Пакистан · 1 центр

• Asian Institute of Medical Sciences — Hyderābād

Публикации

• Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. 2019 May 4. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK548069/ PMID 31689026
• Hammad MAM, Quesada SG, Belczyk AL, Ghoniem GM. Beyond Glycemic Control: Concurrent GLP-1 Receptor Agonist Use Is Associated with Reduced Urinary Adverse Events Following OnabotulinumtoxinA Treatment in Non-Diabetic Adults with Overactive Bladder. Toxins (Basel). 2025 Nov 1;17(11):542. doi: 10.3390/toxins17110542. PMID 41295856
• Sterckx M, De Keyser L. Euglycemic Ketoacidosis Following the Use of Counterfeit Semaglutide for Weight Loss. Cureus. 2026 Jan 30;18(1):e102627. doi: 10.7759/cureus.102627. eCollection 2026 Jan. PMID 41773123
• Ismaiel A, Scarlata GGM, Boitos I, Leucuta DC, Popa SL, Al Srouji N, Abenavoli L, Dumitrascu DL. Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis. Int J Obes (Lond). 2025 Oct;49(10):1946-1957. doi: 10.1038/s41366-025-01859-6. Epub 2025 Aug 13. PMID 40804463
• Kasagga A, Rebellow D, Hashmi T, Husami MY, Lama P, Arul Selvan K, Nakasagga K. Comparative Efficacy and Tolerability of Tirzepatide Versus Semaglutide at Varying Doses for Weight Loss in Non-diabetic Adults With Obesity: A Network Meta-Analysis of Randomized Controlled Trials. Cureus. 2025 Aug 17;17(8):e90335. doi: 10.7759/cureus.90335. eCollection 2025 Aug. PMID 40978842
• Quddos F, Hubshman Z, Tegge A, Sane D, Marti E, Kablinger AS, Gatchalian KM, Kelly AL, DiFeliceantonio AG, Bickel WK. Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Sci Rep. 2023 Nov 28;13(1):20998. doi: 10.1038/s41598-023-48267-2. PMID 38017205
• Ard J, Fitch A, Fruh S, Herman L. Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. Adv Ther. 2021 Jun;38(6):2821-2839. doi: 10.1007/s12325-021-01710-0. Epub 2021 May 11. PMID 33977495
• Thomsen RW, Mailhac A, Lohde JB, Pottegard A. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes Obes Metab. 2025 Apr;27 Suppl 2(Suppl 2):66-88. doi: 10.1111/dom.16364. Epub 2025 Apr 8. PMID 40196933

Идентификаторы

NCT: NCT07513168 · AIMS/ERC/9856/26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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