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.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Mean Percent Change From Baseline in Body Weight at 52 Weeks.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Cohort 1: Obesity Without T2DM
Adults with obesity (BMI ≥30 kg/m²) without type 2 diabetes mellitus, receiving tirzepatide as part of standard clinical care.
干预措施: Tirzepatide (LIPOLESS de Laboratorio de Productos Eticos C.E.I.S.A.) (Drug)
Cohort 2: T2DM With or Without Obesity
Adults with type 2 diabetes mellitus (with or without obesity), receiving tirzepatide as part of standard clinical care.
干预措施: Tirzepatide (LIPOLESS de Laboratorio de Productos Eticos C.E.I.S.A.) (Drug)
结局指标
主要结局
Mean Percent Change From Baseline in Body Weight at 52 Weeks.
时间窗: Baseline and 52 weeks.
Percentage change in total body weight from baseline to week 52 for participants in Cohort A (Adults with obesity without diabetes).
Mean Change From Baseline in Glycated Hemoglobin (HbA1c) at 52 Weeks.
时间窗: Baseline and 52 weeks.
Absolute change in HbA1c levels from baseline to week 52 for participants in Cohort B (Adults with type 2 diabetes).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs).
时间窗: Through week 52.
Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), including gastrointestinal, pancreatic, cardiovascular, and other adverse events occurring during the 52-week treatment period.
次要结局
- Mean Change From Baseline in Body Weight at 52 Weeks.(Baseline and 52 weeks.)
- Mean Change From Baseline in Body Mass Index (BMI) at 52 Weeks.(Baseline and 52 weeks.)
- Percentage of Participants Achieving Body Weight Reduction Thresholds at 52 Weeks.(52 weeks.)
- Change From Baseline in Systolic Blood Pressure at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Diastolic Blood Pressure at 52 Weeks.(Baseline and 52 weeks.)
- Percentage Change From Baseline in Total Cholesterol at 52 Weeks.(Baseline and 52 weeks.)
- Percentage Change From Baseline in LDL Cholesterol (LDL-C) at 52 Weeks.(Baseline and 52 weeks.)
- Percentage Change From Baseline in HDL Cholesterol (HDL-C) at 52 Weeks.(Baseline and 52 weeks.)
- Percentage Change From Baseline in Triglycerides at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Total Fat Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Visceral Fat Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Lean Body Mass Measured by Bioelectrical Impedance Analysis (BIA) at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Fasting Insulin at 52 Weeks.(Baseline and 52 weeks.)
- Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 52 Weeks.(Baseline and 52 weeks.)
- Percentage Change From Baseline in High-sensitivity C-reactive Protein (hs-CRP) at 52 Weeks.(Baseline and 52 weeks.)
- Percentage of Participants Achieving HbA1c Targets (Cohort 2) at 52 Weeks.(52 weeks.)
- Percentage of Scheduled Tirzepatide Doses Successfully Administered Through 52 Weeks.(Through week 52.)
- Percentage of Participants Completing the 52-Week Follow-up Period.(Through week 52.)