BALANCE-OBS: Bofanglutide (GZR18) Versus Semaglutide in Latin American Adults With Overweight or Obesity

BALANCE-OBS: A Multiregional, Randomized, Multicenter, Active-Controlled Confirmatory Phase III Study to Evaluate the Efficacy and Safety of Bofanglutide (GZR18) Versus Semaglutide in Latin American Adults With Overweight or Obesity

The goal of this clinical trial is to evaluate the efficacy and safety of Bofanglutide (GZR18) compared with Semaglutide in Latin American adults with overweight or obesity. It will also evaluate the effects of treatment on metabolic parameters, cardiovascular risk factors, and quality of life.

The main questions it aims to answer are:

Does Bofanglutide (GZR18) reduce body weight after 36 weeks of treatment compared with Semaglutide? What effects does Bofanglutide (GZR18) have on metabolic parameters, cardiovascular risk factors, and quality of life? How safe and well tolerated is treatment with Bofanglutide (GZR18)?

Researchers will compare Bofanglutide (GZR18) with Semaglutide, an active comparator, to evaluate efficacy and safety in adults with overweight or obesity.

Participants will:

Receive Bofanglutide (GZR18) every 2 weeks or Semaglutide once weekly by subcutaneous injection Follow standardized recommendations for diet and physical activity throughout the study Attend scheduled clinic visits for efficacy and safety assessments Participate in treatment and follow-up for up to 40 weeks, including screening, treatment, and safety follow-up periods

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity & Overweight
• Intervention / Treatment: Drug: Bofanglutida; Drug: Semaglutide

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gisselle Vanessa González Hernández, Dr.; Phone Number: 52; Email: gvgonzalez@carnot.com

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiología "Ignacio Chávez"
    • Contact: Diego Araiza Garaygordobil, Dr.; Phone Number: 27303 52 55 5573 2911; Email: dargaray@gmail.com
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Centro de Investigacion Clinica y Medicina Traslacional (CIMeT)
      • Contact: Luis Miguel Román Pintos, Dr.; Phone Number: 52 33 986 9435; Email: luis.roman@academicos.udg.mx
  • Michoacán
    • Morelia, Michoacán, Mexico, 58000
      • CICMEX Centro de Investigación Clínica de México S de RL de CV.
      • Contact: Armando Benítez Cabrera, Dr.; Phone Number: 52 443 298 9405; Email: drarmandobenitezcabrera@gmail.com
  • Querétaro
    • Querétaro City, Querétaro, Mexico, 76070
      • SMIQ, S. de R.L. de C.V.
      • Contact: Juan Carlos Márquez Romero, Dr.; Phone Number: 55 442 224 7516; Email: jcmmdm@gmil.com
  • Sonora
    • Hermosillo, Sonora, Mexico, 83280
      • Investigación Médica Sonora S.C.
      • Contact: Diego Espinoza Peralta, Dr.; Phone Number: 55 662 212 5596; Email: dr.espinoza.peralta@gmail.com
  • Tamaulipas
    • Ciudad Madero, Tamaulipas, Mexico, 89440
      • Centro de Estudios de lnvestigación Metabólicos y Cardiovasculares, S.C.
      • Contact: Rafael Margarito Violante Ortiz, Dr.; Phone Number: 52 833 126 00 55; Email: dr.violante.cei@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants aged ≥18 years.
• Body mass index (BMI): ≥30.0 kg/m² (obesity), or ≥27.0 kg/m² and <30.0 kg/m² (overweight) with at least one weight-related comorbidity, including impaired glucose metabolism, hypertension, dyslipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD), osteoarthritis attributable to excess weight, or obstructive sleep apnea.
• Body weight managed through diet and exercise alone for at least 12 weeks prior to screening, with <5% change in body weight during the previous 12 weeks.
• Willingness and ability to maintain a stable diet and physical activity regimen throughout the study.
• Female participants of reproductive potential must not be pregnant or breastfeeding, must have a negative pregnancy test at screening and prior to randomization, and must agree to use a highly effective method of contraception during the study and for at least 8 weeks after the last dose of study drug.
• Male participants must agree to use effective contraception and refrain from sperm donation during the study and for at least 8 weeks after the last dose of study drug.
• Ability to understand the study requirements and provide written informed consent prior to any study-specific procedures.

Exclusion Criteria:

• Known or suspected hypersensitivity to GLP-1 receptor agonists, GLP-1/GIP receptor agonists, or any component of the investigational product.
• History of substance abuse or alcoholism within 6 months prior to screening.
• Presence of conditions that may interfere with accurate anthropometric assessments.
• History of bariatric surgery or planned bariatric surgery during the study.
• Obesity secondary to an underlying disease or medication.
• Previous diagnosis of diabetes mellitus (except gestational diabetes).
• History of severe hypoglycemia within 6 months prior to screening.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2).
• History of malignancy within 5 years prior to screening, except adequately treated non-melanoma skin cancer or carcinoma in situ.
• Clinically significant thyroid disease, pancreatitis, gallbladder disease, gastrointestinal disease, cardiovascular disease, cerebrovascular disease, hepatic disease, renal disease, or hematologic disease that, in the Investigator's judgment, may interfere with study participation.
• Uncontrolled hypertension or clinically significant electrocardiogram abnormalities.
• Moderate or severe psychiatric disorders, clinically significant eating disorders, suicidal ideation or behavior, or a PHQ-9 score ≥15 at screening.
• Clinically significant laboratory abnormalities at screening, including abnormalities in liver function, renal function, pancreatic enzymes, calcitonin, hematology, glycemic parameters, or positive testing for HIV, active hepatitis B, hepatitis C, or syphilis.
• Prior use of GLP-1 receptor agonists, dual/triple incretin agonists, weight-loss medications, hypoglycemic agents, or other medications that may affect body weight within 3 months prior to screening.
• Acute infection requiring systemic treatment at screening or prior to randomization.
• Participation in another interventional clinical trial within 90 days or 5 half-lives of the investigational product (whichever is longer) prior to randomization.
• History of organ transplantation, major surgery, or severe trauma within 6 months prior to screening.
• Any condition that, in the Investigator's judgment, may compromise participant safety, protocol compliance, or the validity of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Bofanglutida (GZR18),	Drug: Bofanglutida; Bofanglutide (GZR18) is a long-acting GLP-1 receptor agonist administered by subcutaneous injection every 2 weeks. Participants will receive progressive dose titration starting at 3 mg up to a target dose of 48 mg according to the study protocol during the 36-week treatment period.; Other Names: GZR18
Active Comparator: Group B: Semaglutide	Drug: Semaglutide; Semaglutide is a GLP-1 receptor agonist administered by weekly subcutaneous injection with progressive dose titration from 0.25 mg to 1 mg according to the study protocol during the 36-week treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Body Weight From Baseline to Week 36	Evaluation of the percent change in body weight from baseline to Week 36 in participants receiving Bofanglutide (GZR18) compared with Semaglutide.	Baseline to Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Clinically Relevant Weight Reduction	Evaluation of the proportion of participants achieving clinically relevant body weight reductions of ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from baseline to Week 36.	Baseline to Week 36
Change in Body Mass Index (BMI) From Baseline at Week 36	Evaluation of the change in body mass index (BMI), expressed in kg/m², from baseline to Week 36 during treatment	Baseline to Week 36
Change in Hemoglobin A1c (HbA1c) From Baseline at Week 36	Evaluation of the change in glycated hemoglobin (HbA1c), expressed as percentage (%), from baseline to Week 36 during treatment	Baseline to Week 36
Change in Fasting Plasma Glucose From Baseline at Week 36	Evaluation of the change in fasting plasma glucose concentration from baseline to Week 36 during treatment	From Baseline at Week 36
Change in Systolic Blood Pressure From Baseline at Week 36	Evaluation of the change in systolic blood pressure from baseline to Week 36 during treatment	Baseline to Week 36
Change in Diastolic Blood Pressure From Baseline at Week 36	Evaluation of the change in diastolic blood pressure from baseline to Week 36 during treatment	Baseline to Week 36
Change in Total Cholesterol From Baseline at Week 36	Evaluation of the change in total cholesterol concentration from baseline to Week 36 during treatment	Baseline to Week 36
Change in Triglycerides From Baseline at Week 36	Evaluation of the change in fasting triglyceride concentration from baseline to Week 36 during treatment	Baseline to Week 36
Change in Impact of Weight on Quality of Life-Lite (IWQOL-Lite) Total Score From Baseline at Week 36	Evaluation of the change in the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) total score from baseline to Week 36 during treatment. Scores range from 0 to 100, with higher scores indicating better weight-related quality of life.	Baseline to Week 36
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Evaluation of safety and tolerability based on adverse events, serious adverse events, laboratory assessments, and treatment discontinuations during the study.	From first dose through safety follow-up (up to 40 weeks)
Change in Patient Health Questionnaire-9 (PHQ-9) Total Score From Baseline at Week 40	Evaluation of the change in the Patient Health Questionnaire-9 (PHQ-9) total score from baseline to Week 40. The PHQ-9 is a self-administered questionnaire used to assess depressive symptoms. Total scores range from 0 to 27, with higher scores indicating more severe depressive symptoms.	From first dose through safety follow-up (up to 40 weeks)
Number of Participants With Suicidal Ideation or Behavior Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	Evaluation of the occurrence of suicidal ideation or suicidal behavior during treatment with Bofanglutide (GZR18) compared with Semaglutide, assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS).	From first dose through safety follow-up (up to 40 weeks)
Incidence of Anti-Drug Antibodies Against Bofanglutide	Evaluation of the incidence of anti-drug antibodies (ADAs) against Bofanglutide during the study, including assessment of neutralizing antibodies (NAbs) and cross-reactivity with endogenous glucagon-like peptide-1 (GLP-1), as applicable.	From first dose through safety follow-up (up to 40 weeks)
Early Assessment at Week 16	Evaluation of the percent change in body weight from baseline and the proportion of participants achieving body weight reductions of ≥5% and ≥10% at Week 16.	Baseline to Week 16

Collaborators and Investigators

• Sponsor: Carnot Laboratories
• Investigators: Principal Investigator: Emma Adriana Chávez Manzanera, Dr., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Clínica de Obesidad y Trastornos de la Conducta Alimentaria

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; semaglutide
• Other Study ID Numbers: PC-ECI-CM-102-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data collected during this study will not be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No