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

Summary

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.

Timeline

Start

2025-08-01

Primary completion

2026-08-30

Completion

2026-12-01

Publications

• Background 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/
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.
• Background Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, Brar R, Baker C, Gluckman TJ, Stucky NL. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024 Sep 1;184(9):1056-1064. doi: 10.1001/jamainternmed.2024.2525.
• Background Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831.
• Background Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19.
• Background Tan HC, Dampil OA, Marquez MM. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. J ASEAN Fed Endocr Soc. 2022;37(2):65-72. doi: 10.15605/jafes.037.02.14. Epub 2022 Aug 23.
• Background Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224.
• Background Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27.
• Background Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med. 2023 Apr;33(3):159-166. doi: 10.1016/j.tcm.2021.12.008. Epub 2021 Dec 21.
• Background Ryan DH, Lingvay I, Deanfield J, Kahn SE, Barros E, Burguera B, Colhoun HM, Cercato C, Dicker D, Horn DB, Hovingh GK, Jeppesen OK, Kokkinos A, Lincoff AM, Meyhofer SM, Oral TK, Plutzky J, van Beek AP, Wilding JPH, Kushner RF. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024 Jul;30(7):2049-2057. doi: 10.1038/s41591-024-02996-7. Epub 2024 May 13.
• Background Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10.
• Background Elmaleh-Sachs A, Schwartz JL, Bramante CT, Nicklas JM, Gudzune KA, Jay M. Obesity Management in Adults: A Review. JAMA. 2023 Nov 28;330(20):2000-2015. doi: 10.1001/jama.2023.19897.
• Background Bergmann NC, Davies MJ, Lingvay I, Knop FK. Semaglutide for the treatment of overweight and obesity: A review. Diabetes Obes Metab. 2023 Jan;25(1):18-35. doi: 10.1111/dom.14863. Epub 2022 Oct 18.
• Background Moiz A, Levett JY, Filion KB, Peri K, Reynier P, Eisenberg MJ. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Am J Cardiol. 2024 Jul 1;222:121-130. doi: 10.1016/j.amjcard.2024.04.041. Epub 2024 Apr 26.

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