Semaglutide for Post-Transplant Diabetes

(SPOT-DM Trial)

Not yet recruiting at 1 trial location

Overseen By Vesta Lai

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University Health Network, Toronto

Must not be taking: Glucose-lowering therapy, GLP1RA

Disqualifiers: Diabetes, Pancreatitis, Stroke, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests semaglutide to evaluate its effectiveness and safety for individuals at risk of developing diabetes after a kidney transplant. Participants will receive either semaglutide or a placebo, which contains no active medicine, to compare outcomes. Suitable candidates are adults who recently underwent a kidney transplant and show signs of potential diabetes, such as elevated blood sugar levels or a high body mass index (BMI). As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using glucose-lowering therapy for diabetes or have used GLP1RA in the 30 days before screening.

Is there any evidence suggesting that semaglutide is likely to be safe for humans?

Research has shown that semaglutide can significantly lower blood sugar levels and aid in weight loss for patients who have had a kidney transplant. Studies also indicate that it is generally safe and well-tolerated for treating diabetes after a liver transplant.

Although semaglutide is not yet specifically recommended for kidney transplant recipients, ongoing research aims to confirm its safety and effectiveness for them. Researchers remain hopeful about its safety but continue to gather evidence for kidney transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post-transplant diabetes?

Researchers are excited about semaglutide for post-transplant diabetes because it offers a novel approach by targeting the GLP-1 receptor, which helps regulate blood sugar levels. Unlike traditional treatments that might primarily focus on insulin or other medications, semaglutide is an oral medication that provides a more convenient administration method. This could lead to better adherence and potentially improved outcomes for patients. Additionally, semaglutide's ability to be titrated based on tolerance allows for personalized dosing, which could minimize side effects and optimize effectiveness.

What evidence suggests that semaglutide might be an effective treatment for post-transplant diabetes?

Studies have shown that semaglutide, the investigational treatment in this trial, can significantly lower HbA1c levels, a measure of blood sugar control, and aid in weight loss for kidney transplant patients with diabetes. One study found that patients experienced a noticeable drop in their average HbA1c levels after six months of treatment. Semaglutide belongs to a group of drugs called GLP-1 receptor agonists, which have been linked to better survival rates for both patients and their transplanted kidneys. Although more research is needed to confirm these benefits, early results are promising for those managing diabetes after a kidney transplant. ^{1 2 3 5 6}

Who Is on the Research Team?

Sunita Singh, MD MSc FRCPC

Principal Investigator

University Health Network, Toronto General Hospital

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients at risk of developing diabetes after their transplant. Participants should be adults who have recently received a kidney transplant and are currently free from diabetes but at high risk of developing it.

Inclusion Criteria

I had a kidney transplant 4 to 12 weeks ago.

At risk for PTDM at the time of transplant based on specific criteria: BMI ≥ 25 kg/m2, or Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or 2hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or HbA1C 5.5-6.4% (at risk for DM or prediabetes)

Signed and dated written informed consent

Exclusion Criteria

I have received a kidney and pancreas transplant.

With known or suspected hypersensitivity to semaglutide or related products

Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or placebo for 24 weeks to assess efficacy in preventing post-transplant diabetes mellitus

24 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The study tests the effectiveness and safety of Semaglutide, a medication used to control blood sugar levels, in preventing diabetes in people who've had a kidney transplant. It compares different doses (3 MG, 7 MG, 14 MG) with a placebo over 24 weeks.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 3 Interventions

Patients will be up-titrated as tolerated starting at 3 mg oral semaglutide once daily for 4 weeks, followed by 7 mg oral semaglutide once daily for 4 weeks and then 14 mg oral semaglutide once daily for 16 weeks. Semaglutide can be down-titrated to previously tolerated dose if the current dose is not tolerated by the participant.

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a 12-week trial involving 75 adults with type 2 diabetes, semaglutide significantly improved both first- and second-phase insulin secretion, indicating enhanced beta cell function.

Semaglutide also led to better glycaemic control, with reduced fasting and postprandial glucose levels, and was well tolerated by participants, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Kapitza, C., Dahl, K., Jacobsen, JB., et al.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective for treating type 2 diabetes and obesity, providing significant weight loss and cardiovascular benefits, making it crucial for high-risk patients.

However, during the SUSTAIN clinical trial program, a safety concern arose regarding the worsening of diabetic retinopathy, potentially linked to rapid reductions in HbA1c levels, which requires further investigation and careful clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. Cigrovski Berkovic, M., Strollo, F.[2023]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively lower hemoglobin A1c levels by approximately -1.5% and reduce body weight by about -4.5 kg in phase 3 trials, demonstrating comparable efficacy to dulaglutide.

While semaglutide offers cardiovascular benefits, including a reduced risk of major cardiovascular events, it is associated with an increased risk of retinopathy complications in patients with existing diabetic retinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. Miles, KE., Kerr, JL.[2021]

In the SUSTAIN 1 to 5 trials involving 3918 participants with type 2 diabetes, semaglutide significantly helped more individuals achieve their HbA1c targets (47% to 74%) compared to placebo (7% to 19%) and other active comparators (16% to 29%).

Semaglutide was effective in achieving these results while minimizing unwanted outcomes, such as weight gain, severe hypoglycaemia, and gastrointestinal side effects, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. DeVries, JH., Desouza, C., Bellary, S., et al.[2022]

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively improve blood sugar control and promote weight loss, with a favorable safety profile similar to other GLP-1RAs, based on extensive phase 3 trials including cardiovascular outcome studies.

The most common side effects of semaglutide are mild-to-moderate gastrointestinal disturbances, and while there are concerns about pancreatic and thyroid cancer, no unexpected safety issues have been identified, making it a beneficial option for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. Smits, MM., Van Raalte, DH.[2023]

In a post hoc analysis of 5,119 subjects from the SUSTAIN clinical trials, semaglutide (0.5 and 1.0 mg) led to significantly higher rates of achieving both ≥1.0% HbA1c reduction and ≥5.0% weight loss compared to other diabetes treatments, with rates ranging from 25% to 59% for semaglutide versus 2% to 23% for comparators.

Semaglutide was well tolerated and exhibited a safety profile similar to other GLP-1 receptor agonists, indicating it is a safe and effective option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GREATER COMBINED REDUCTIONS IN HbA1C ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Rodbard, HW., Bellary, S., Hramiak, I., et al.[2022]

In a phase 3 trial involving 388 treatment-naive patients with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.45% with 0.5 mg and 1.55% with 1.0 mg doses compared to placebo, indicating its efficacy in improving glycaemic control.

Semaglutide also led to significant weight loss, with reductions of 3.73 kg and 4.53 kg for the respective doses, while maintaining a safety profile similar to existing GLP-1 receptor agonists, with most adverse events being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Sorli, C., Harashima, SI., Tsoukas, GM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11016780/

Safety and efficacy of semaglutide in post kidney transplant ... Semaglutide was found to significantly reduce HbA1c levels and weight in post renal transplant patients with diabetes.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213858724003711

GLP-1 receptor agonists in kidney transplant recipients ... GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05702931

Semaglutide Treatment for Hyperglycaemia After Renal ... The efficacy of semaglutide is untested in renal transplant recipients, and safety concerns remain, primarily on renal graft function.

4. elsevier.es elsevier.es/en-revista-annals-hepatology-16-articulo-semaglutide-for-treatment-post-transplantation-S1665268125001450

Semaglutide for the treatment of post transplantation ... In 10 patients (mean±SEM, age 54±5 years), 6 months treatment with semaglutide resulted in a significant decrease of median HbA1c from 66.1 (32.2-80.2) to 48.0 ...

5. nyulangone.org nyulangone.org/news/anti-obesity-drugs-benefit-kidney-transplant-recipients-type-2-diabetes

Anti-Obesity Drugs Benefit Kidney Transplant Recipients ... Kidney transplant recipients with type 2 diabetes treated with a new class of anti-obesity drugs were less likely to experience organ failure and survived ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38623181/

Safety and efficacy of semaglutide in post kidney transplant ... Semaglutide was found to significantly reduce HbA1c levels and weight in post renal transplant patients with diabetes.