Efficacy, Safety, and Tolerability of Tirzepatide in Real-World Conditions in Paraguay.

Official title

Prospective Cohort Study to Evaluate the Efficacy, Safety, and Tolerability of Tirzepatide in Real-World Conditions in Persons With Obesity Without Diabetes and Type 2 Diabetes Mellitus With or Without Obesity in Paraguay.

Overview

This is a prospective cohort study evaluating the efficacy, safety, and tolerability of tirzepatide under real-world conditions in the Paraguayan population. The study includes two cohorts: Cohort 1 consists of adults with obesity (BMI ≥30 kg/m²) without type 2 diabetes mellitus (T2DM), and Cohort 2 consists of adults with T2DM with or without obesity. Each cohort will enroll 80 participants (160 total). All participants will receive tirzepatide as part of their standard clinical care and will be followed for 52 weeks with visits approximately every 6 weeks. Primary outcomes include percentage change in body weight from baseline at week 52 (Cohort 1) and change in HbA1c and body weight at week 52 (Cohort 2). Safety outcomes include adverse event rates. The study is conducted at Las Rias Medical Center, Asuncion, Paraguay, and has been approved by the CEI-INCAN Ethics Committee and authorized by DINAVISA.

Detailed description

Innovation and Regional Significance This study represents a pioneering milestone as the first prospective, long-term real-world evidence (RWE) investigation of tirzepatide in Paraguay. While global randomized clinical trials have established efficacy within controlled environments, this research addresses a critical knowledge gap by evaluating the performance of dual GIP/GLP-1 receptor agonism within a South American cohort. By documenting metabolic outcomes, safety, and adherence under routine clinical conditions-shaped by unique genetic, dietary, and socioeconomic factors-this project provides essential data for the regional medical community and sets a new benchmark for metabolic excellence in the region.

Study Design and Long-Term Follow-Up

The study is structured as a 52-week prospective cohort investigation, a duration that exceeds most regional observational studies, allowing for the assessment of weight loss maintenance and long-term glycemic stability. Participants are divided into two distinct metabolic profiles:

* Cohort 1 (Obesity Focus): Adults with BMI ≥30 kg/m² without T2DM. * Cohort 2 (Metabolic Synergy): Adults with T2DM, with or without obesity. This dual-track approach allows for a comprehensive analysis of tirzepatide's pleiotropic effects across the spectrum of metabolic disease.

Treatment Protocol and Nutritional Support All participants receive tirzepatide (Lipoless by Laboratorio de Productos Eticos C.E.I.S.A) via subcutaneous injection once weekly. The treatment follows a standardized titration schedule starting at 2.5 mg, with dose escalations every 4 weeks based on individual clinical response and gastrointestinal tolerability. The pharmacological intervention is supported by a structured hyperproteic, low-carbohydrate nutritional plan (approximately 1,500 kcal/day) aimed at optimizing metabolic results and supporting healthy weight loss. Furthermore, in alignment with standard medical practice, all subjects are prescribed a standardized physical activity regimen and comprehensive healthy lifestyle modifications to ensure a holistic approach to long-term metabolic health.

Advanced Monitoring and Diagnostics To ensure high-quality data collection, the study utilizes precise diagnostic tools at specific intervals:

* Body Composition: Systematic use of bioelectrical impedance analysis (InBody) to monitor changes in fat mass, visceral fat, and lean body mass at every visit. * Imaging: Standardized abdominal and thyroid ultrasound evaluations conducted at the Instituto Radiológico Calvo (weeks 0, 24, 52). * Functional Assessment: Measurement of muscle strength to correlate pharmacological efficacy with physical performance at very visit * Biochemical Analysis: Comprehensive laboratory panels processed by Laboratorio Díaz Gill to monitor glycemic control, lipid profiles, and safety markers (weeks 0, 24, 52).

Regulatory Rigor and Safety Operating under the strict oversight of the CEI-INCAN Ethics Committee and with the authorization of DINAVISA, the study adheres to International Council for Harmonisation (ICH) Good Clinical Practice guidelines. Safety is monitored through a robust pharmacovigilance system, with a specific focus on gastrointestinal tolerability and hepatobiliary safety, recorded via the PowerMed electronic data capture system.

Exclusionary Clarity In order to isolate the specific effects of incretin-based therapy in a real-world setting, this study strictly excludes patients using insulin, focusing on the potential of tirzepatide as a foundational therapy for metabolic health.

Interventions

• Drug Tirzepatide (LIPOLESS de Laboratorio de Productos Eticos C.E.I.S.A.)
  Participants will receive subcutaneous injections of tirzepatide (LIPOLESS de Laboratorio de Productos Eticos C.E.I.S.A.) once weekly. The dosage will be adjusted according to standard clinical practice and the investigator's discretion, following the manufacturer's titration schedule (starting at 2.5 mg and increasing up to 15 mg as tolerated).

Primary outcome measures

• Mean Percent Change From Baseline in Body Weight at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Mean Change From Baseline in Glycated Hemoglobin (HbA1c) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs). [Time frame: Through week 52.]

Secondary outcome measures (12)

• Mean Change From Baseline in Body Weight at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Mean Change From Baseline in Body Mass Index (BMI) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Percentage of Participants Achieving Body Weight Reduction Thresholds at 52 Weeks. [Time frame: 52 weeks.]
• Change From Baseline in Systolic Blood Pressure at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Change From Baseline in Diastolic Blood Pressure at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Percentage Change From Baseline in Total Cholesterol at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Percentage Change From Baseline in LDL Cholesterol (LDL-C) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Percentage Change From Baseline in HDL Cholesterol (HDL-C) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Percentage Change From Baseline in Triglycerides at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Change From Baseline in Total Fat Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Change From Baseline in Visceral Fat Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks. [Time frame: Baseline and 52 weeks.]
• Change From Baseline in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks. [Time frame: Baseline and 52 weeks.]

Eligibility criteria

Inclusion criteria

• Age between 18 and 70 years at the time of informed consent.
• Stable residence in Paraguay for at least 12 months prior to screening.
• Ability to provide written informed consent and comply with all study procedures.
• Sufficient proficiency in the Spanish language to complete questionnaires and follow study instructions.
• Clinical stability, defined as the absence of hospitalization related to diabetes or obesity complications within 3 months prior to screening.
• Adequate renal function, defined as an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m² calculated using the CKD-EPI equation.
• For participants enrolled in the obesity cohort: clinical diagnosis of obesity with BMI ≥30 kg/m², no prior diagnosis of diabetes mellitus (HbA1c <6.5%), and at least one documented unsuccessful attempt at dietary weight-loss intervention within the previous 12 months.
• For participants enrolled in the type 2 diabetes mellitus (T2DM) cohort: established diagnosis of T2DM for at least 6 months prior to screening according to ADA 2025 criteria, HbA1c between 7.0% and 9.5% at screening confirmed at baseline, BMI ≥24 kg/m², and stable treatment on monotherapy or dual therapy with metformin, sulfonylureas, DPP-4 inhibitors, or SGLT-2 inhibitors for at least 3 months prior to screening.

Exclusion criteria

• Diagnosis of type 1 diabetes mellitus or secondary causes of diabetes.
• History of diabetic ketoacidosis within 12 months prior to screening.
• Current or recent use (within 3 months prior to screening) of GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists.
• Current or prior use of insulin therapy for the management of diabetes.
• Clinically significant untreated thyroid dysfunction, including hypothyroidism or hyperthyroidism.
• Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
• Major adverse cardiovascular event (MACE), including acute myocardial infarction, stroke, or hospitalization for heart failure within 6 months prior to screening.
• Heart failure classified as New York Heart Association (NYHA) Functional Class III or IV.
• Uncontrolled hypertension, defined as systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg despite optimal antihypertensive therapy.
• History of acute or chronic pancreatitis.
• Active inflammatory bowel disease or prior bariatric surgery.
• Clinically significant diabetic gastroparesis or other gastrointestinal motility disorders that may interfere with the absorption of concomitant oral medications.
• Use of systemic corticosteroids for more than 14 consecutive days within 3 months prior to screening.
• Treatment with oral anti-obesity medications (including orlistat, phentermine, naltrexone/bupropion, or topiramate) within 3 months prior to screening.
• Participation in another clinical trial involving an investigational medicinal product within 30 days prior to screening.
• Moderate to advanced chronic kidney disease defined as eGFR <45 mL/min/1.73m² or requirement for dialysis.
• Active liver disease or transaminase levels (ALT/AST) greater than 3 times the upper limit of normal.
• Active malignancy or history of cancer within the previous 5 years, except for completely resected basal cell or squamous cell skin carcinoma.
• Uncontrolled major psychiatric disorders or history of suicide attempt within the previous 2 years.
• Confirmed or suspected pregnancy, including positive serum beta-hCG test at screening, or active breastfeeding.
• Intention to become pregnant during the study period.
• Women of childbearing potential unwilling to use effective contraceptive methods (hormonal, intrauterine, or dual-barrier) throughout the study and for 3 months after the final dose.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Paraguay · 1 center

• Centro Médico Las Rias — Asunción

Identifiers

NCT: NCT07588438 · Eticos 01/25 V 1.1 03/12/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗