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

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.