Semaglutide for Post-Transplant Diabetes

(SPOT-DM Trial)

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

74 Participants Needed

Trial Summary

What is the purpose of this trial?

The study aims to determine the short-term efficacy, mechanisms and safety of 24 weeks of placebo and semaglutide therapy in 74 KTR at risk of post-transplant diabetes mellitus (PTDM).

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.

What data supports the effectiveness of the drug semaglutide for post-transplant diabetes?

Semaglutide has been shown to help control blood sugar levels in people with type 2 diabetes, including those who have had a liver transplant, by lowering hemoglobin A1c levels. It also offers benefits like weight loss and reduced risk of heart-related issues, although more studies are needed specifically for post-transplant patients. ^{1 2 3 4 5}

Is semaglutide generally safe for humans?

Semaglutide is generally considered safe for humans, with most side effects being mild to moderate, such as stomach issues. It may increase the risk of gallbladder problems and should be used carefully in people with existing eye conditions related to diabetes. Overall, it has a favorable safety profile similar to other drugs in its class. ^{3 4 6 7 8}

How is the drug semaglutide unique for treating post-transplant diabetes?

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that not only helps control blood sugar levels but also promotes weight loss and offers cardiovascular benefits, which are important for patients with diabetes. It can be administered either orally or as a weekly injection, providing flexibility in treatment options. ^{2 3 4 9 10}

Research Team

Sunita Singh, MD MSc FRCPC

Principal Investigator

University Health Network, Toronto General Hospital

Eligibility Criteria

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

I haven't had a heart attack, mini-stroke, or stroke in the last 30 days.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Initiation in a Type 2 Diabetes Mellitus, Post-Liver Transplant Patient. [2022]

2. Germany 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Semaglutide for the Treatment of Type 2 Diabetes Mellitus. [2021]

4. England 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. [2022]

5. England 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

GREATER COMBINED REDUCTIONS IN HbA1C ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. [2022]