Glucagon-like-peptide-1 Receptor Agonists in Patients Receiving Maintenance Dialysis

Phase 4

Not yet recruiting

• Conditions: Kidney Disease, Chronic; Diabetes; Dialysis; End Stage Kidney Disease (ESRD)
• Interventions: Drug: Semaglutide Pen

• Registration Number: NCT07017270
• Lead Sponsor: Unity Health Toronto

Brief Summary

This study aims to determine if GLP1RA is safe and tolerable in maintenance dialysis population, adherence, and feasibility of a larger definitive cardiovascular outcome trial in this population. Participants will be randomized 1:1 to either weekly subcutaneous semaglutide versus usual care and followed for 26 weeks.

Detailed Description

In this randomized pilot study, Individuals randomized to the active intervention arm will take semaglutide once weekly. Semaglutide (injectable, 1.34 mg/mL) is delivered subcutaneously via a multiple-use pen-injector that can be used to dial in all required doses on the same pen-injector. The clinical pen has a drum scale of 1-80 in increments of 1. Participants will be trained/re-trained on injector use at 0, 4, 8, and 12 weeks. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel. Semaglutide will be titrated using an algorithm used in previous trials with a starting dose of 0.25 mg/week, with an increase to 0.5 mg/week after 4 weeks, and to the maximum dose of 1.0 mg/week after 8 weeks as tolerated. If a participant experiences an adverse effect, efforts will be made to maintain the current dosage, with dose reductions or treatment pauses permitted at the discretion of the site investigator. Patient receiving concomitant insulin therapy will have therapy adjusted as per a pre-specified algorithm. Participants allocated to the usual care arm will receive usual care.

Primary outcomes:

1. Feasibility of study recruitment: ≥ 40% of fully eligible patients consent to participate in the trial.

2. Adherence to intervention: ≥ 70% of enrolled patients are adherent to the study intervention over the 26-week follow-up period.

3. Ability to follow: ≥ 90% of participants will be successfully followed to week

Secondary outcomes:

* Proportion Discontinuing Intervention

* Safety Events

* Major Adverse Cardiovascular Outcomes (Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event)

* Body Weight/BMI

* Systolic/diastolic blood pressure

* Insulin dosage, glycemic control (HbA1c and random glucose)

* Lipid profile

* Hemoglobin, Calcium, Phosphate, PTH

* EQ-5D-5L for baseline-adjusted changes in quality of life and symptom burden

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-24
• Study First Submitted QC: 2025-06-03
• Last Update Submitted: 2025-06-03
• Study First Posted: 2025-06-12
• Last Update Posted: 2025-06-12
• Study Start: 2025-07
• Primary Completion: 2027-07
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Age ≥ 18
2. Receiving chronic maintenance hemodialysis or peritoneal dialysis for ≥ 90 days
3. confirmed DM2 based on medical history and current or prior receipt of an oral hypoglycemic agent and/or insulin.
4. Ability to provided informed consent or through their substitute decision maker

Exclusion Criteria

1. Type 1 DM
2. Use of a GLP-1-RA within 30 days prior to screening
3. Personal or first-degree relative(s) with a history of type 2 multiple endocrine neoplasia syndrome or medullary thyroid cancer, or acute pancreatitis (within 180 days of study screening)
4. Confirmed pregnancy, women of childbearing potential
5. Known hypersensitivity to GLP-1-RA
6. Expected to recover kidney function, stop hemodialysis, pursue palliative care, or transplantation within 6 months
7. Enrolment in another clinical trial judged by the investigator to interact with the effect of GLP1-RA

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide	Semaglutide Pen	Individuals randomized to this arm will take semaglutide once weekly.

Primary Outcome Measures

Name	Time	Method
Adherence of Study Intervention	26 weeks	This will be determined if ≥ 70% of enrolled number of eligible participants (who are randomized) are adherent to the study intervention over the 26-week follow-up period.

Secondary Outcome Measures

Name	Time	Method
Study Medication Discontinuation	26 weeks	To determine the proportions of enrolled number of participants who permanently discontinue the study medication in the semaglutide arm.
Feasibility of Study Recruitment	26 weeks	This will be determined if ≥ 40% of the number of fully eligible participants (potential participants who were screened and identified to meet inclusion/exclusion criteria) consent to participate in the trial.
Safety Events of Special Interest	26 weeks	To identify safety events of special interest such as gastrointestinal symptoms, acute biliary disease, acute pancreatitis, interventions for diabetic retinopathy, heart failure exacerbations, malignant neoplasms, and the number of hypoglycemic events.
Major Adverse Cardiovascular Events	26 weeks	This is a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event.
Follow Up Percentage at 26 weeks	26 weeks	To determine if ≥ 90% of participants (who are enrolled) will be successfully followed to week 26 (end of study participation).
Patient Reported Measures	26 weeks	The validated EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) score will be used to evaluate baseline-adjusted changes in quality of life and symptom burden. The EQ-5D-5L asks individuals to rate their overall health on a visual scale from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health.

Trial Locations

Locations (1)

Unity Health Toronto; 🇨🇦 Toronto, Ontario, Canada