Tirzepatide
Conditions
Brief summary
Post-transplant obesity is a common complication after kidney transplantation, largely attributed to recovery from uremia, increased appetite, sedentary lifestyle, and long-term corticosteroid exposure. Obesity in kidney transplant recipients increases the risk of cardiovascular disease, post-transplant diabetes mellitus (PTDM), and may contribute to graft injury through hyperfiltration-related mechanisms, potentially leading to reduced graft survival. Current approaches for weight management in transplant recipients, including lifestyle modification, are often insufficient, while bariatric surgery carries considerable risks and concerns regarding altered absorption of immunosuppressive medications. Tirzepatide (Iranian brand name: Spartina), the first dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated superior effects on weight reduction and glycemic control compared with earlier GLP-1 receptor agonists in the general population. However, its use in kidney transplant recipients requires careful evaluation due to potential gastrointestinal adverse effects, dehydration risk, and possible interaction with calcineurin inhibitor absorption caused by delayed gastric emptying. This prospective single-arm pilot clinical trial aims to assess the preliminary safety and efficacy of tirzepatide in obese kidney transplant recipients with stable graft function. Outcomes include changes in anthropometric indices, percent weight change, gastrointestinal tolerability, immunosuppressive drug trough levels, and graft function over 24 weeks of treatment.
Detailed description
Obesity following kidney transplantation is a frequent metabolic complication, related to improved appetite after resolution of uremia, reduced physical activity, and corticosteroid therapy. Post-transplant obesity is associated with increased risk of cardiovascular disease, PTDM, and chronic graft dysfunction. In addition, obesity-related hyperfiltration may accelerate structural injury to the transplanted kidney, potentially contributing to glomerulopathy and reduced graft survival. Pharmacologic management of obesity in kidney transplant recipients remains challenging. Lifestyle-based interventions often fail to produce sustained weight loss. Bariatric surgery may be effective but is associated with increased risks in transplant recipients, including adhesions, infection, and altered absorption of immunosuppressive agents. Tirzepatide is a dual GIP and GLP-1 receptor agonist with robust effects on weight reduction and glycemic control. Nevertheless, its safety profile in kidney transplant recipients remains insufficiently studied, particularly regarding gastrointestinal adverse events, dehydration risk, and the potential impact on immunosuppressive drug exposure due to delayed gastric emptying. This study is designed as a prospective single-arm pilot clinical trial. Eligible kidney transplant recipients with obesity and stable graft function will receive weekly subcutaneous tirzepatide for 24 weeks using a stepwise dose escalation regimen. Participants will be monitored for changes in body weight, BMI, waist circumference, graft function parameters (serum creatinine and eGFR), metabolic indices (fasting glucose, HbA1c, lipid profile), gastrointestinal adverse events, and calcineurin inhibitor trough levels (tacrolimus or cyclosporine). This pilot trial will provide preliminary evidence regarding feasibility, safety, and potential efficacy of tirzepatide in this high-risk transplant population and may guide the design of larger randomized controlled trials.
Interventions
DRUGTirzepatide
* Route: Subcutaneous injection (SC) * Frequency: Once weekly * Duration: 24 weeks * Dose escalation: * Weeks 1-4: 2.5 mg weekly * Weeks 5-8: 5 mg weekly (if tolerated) * Weeks 9-24: Continue 5 mg weekly or increase to 7.5 mg weekly based on tolerability and physician judgment
Sponsors
Shahid Beheshti University of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Kidney transplant recipient with ≥12 months since transplantation * BMI ≥ 27 kg/m² * Stable graft function in the last 3 months (serum creatinine variation \< 20%) * Stable immunosuppressive regimen * Ability to provide written informed consent
Exclusion criteria
* History of pancreatitis * Severe gastroparesis * History of medullary thyroid carcinoma (MTC) or MEN2 syndrome * eGFR \< 30 mL/min/1.73m² * Acute rejection episode within the past 6 months * Any condition judged by the investigator to interfere with study participation or safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline at Week 24 | Baseline to Week 24 | Percent change in body weight compared to baseline |
| Incidence of Gastrointestinal Adverse Events | Baseline to Week 24 (monthly assessment) | Number of participants with gastrointestinal adverse events ( nausea, vomiting, diarrhea, constipation, abdominal pain) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Change in Serum Creatinine | Baseline to Week 24 | Change from baseline in serum creatinine (mg/dl). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index (BMI) | Baseline to Week 24 | changes in BMI |
| Change in Waist Circumference | Baseline to Week 24 | changes in centimeters |
| Proportion of Participants Achieving Clinically Meaningful Weight Loss • Definition | week 24 | ≥5% and ≥10% weight loss from baseline |
| change in tacrolimus trough Level | Monthly monitoring through Week 24 | Change from baseline in tacrolimus trough level (ng/ml) |
| Change in Fasting blood glucose | Baseline to Week 24 | change from baseline in fasting blood glucose (mg/dl). |
| Change in systolic blood pressure | Baseline to Week 24 | changes from baseline in systolic blood pressure(mmHg). |
| Change in Proteinuria | Baseline to Week 24 | Urine protein-to-creatinine ratio (UPCR) or 24-hour urine protein |
| Change in diastolic blood pressure | Baseline to week 24 | Change from baseline in diastolic blood pressure (mmHg). |
Countries
Iran
Contacts
CONTACTNooshin Dalili, MD
PRINCIPAL_INVESTIGATORNooshin Dalili
SBMU
Outcome results
None listed