Semaglutide for Cystic Fibrosis-Related Diabetes

Overseen By Brooke Noren

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Minnesota

Must be taking: Insulin

Must not be taking: Systemic glucocorticoids

Disqualifiers: Thyroid cancer, Pulmonary exacerbation, GI problems, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of semaglutide as an additional treatment for adults who are overweight or obese and have cystic fibrosis-related diabetes (CFRD). The goal is to determine if semaglutide, typically used for weight management and blood sugar control, can assist alongside insulin. The trial targets adults already on insulin who require enzyme supplements for digestion. It is open to individuals diagnosed with CFRD and a BMI over 26. As a Phase 2, Phase 3 trial, this study evaluates semaglutide's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to important research.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, it is an add-on therapy to insulin, so you will continue your insulin treatment.

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

Research has shown that semaglutide, the treatment being tested in this trial, is well tolerated by adults with diabetes related to cystic fibrosis (CFRD). Reports from cases where semaglutide was added to other treatments suggest it helps control blood sugar and improve metabolism. In a study with five adults who had CFRD and were also obese, semaglutide was used for at least two years without any serious safety issues. These findings suggest that semaglutide can be a safe option for managing CFRD in overweight or obese adults. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis-related diabetes?

Researchers are excited about semaglutide for cystic fibrosis-related diabetes (CFRD) because it offers a unique approach compared to standard insulin therapy. Unlike traditional treatments that primarily focus on managing blood sugar levels, semaglutide is a GLP-1 receptor agonist, which not only helps control glucose but also aids in weight management. This dual action is particularly beneficial for overweight or obese patients with CFRD. Furthermore, semaglutide's mechanism of enhancing insulin secretion and reducing appetite can potentially improve overall metabolic health in this population.

What evidence suggests that semaglutide might be an effective treatment for cystic fibrosis-related diabetes?

Studies have shown that semaglutide can lower blood sugar by increasing insulin release and aiding in weight loss. Research on similar medications in people with cystic fibrosis has demonstrated better blood sugar control and weight loss, with some even discontinuing insulin therapy. Some patients also experienced improved lung function. Although limited data exists specifically for diabetes related to cystic fibrosis, these findings suggest that semaglutide could be promising for managing this condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Amir Moheet, MBBS

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults over 18 with cystic fibrosis-related diabetes (CFRD), overweight/obese (BMI >26 kg/m2), on insulin, and with pancreatic insufficiency can join. They must not be pregnant or breastfeeding, have certain thyroid cancers or endocrine syndromes, severe liver/kidney disease, recent acute lung issues, chronic GI problems requiring hospitalization within a year, history of pancreatitis or gastroparesis, started new CFTR therapy in the last 24 weeks, have suicidal tendencies or eating disorders.

Inclusion Criteria

I am being treated for pancreatic insufficiency with enzyme replacement.

I am 18 or older with cystic fibrosis-related diabetes and on insulin.

You weigh more than what is considered healthy for your height.

Exclusion Criteria

Pregnancy or lactation

You have tried to hurt yourself on purpose in the past, or you are currently thinking about hurting yourself.

I have severe liver disease due to cystic fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly semaglutide therapy as an add-on to insulin for overweight/obese adults with CFRD

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants may be monitored for long-term safety and data analysis

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The trial is testing Semaglutide as an additional treatment to insulin for adults with CFRD who are overweight. It's an open label study where all participants know they're receiving the medication to assess its safety and how well it's tolerated.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

This open label, single arm pilot study, will examine the safety and tolerability of GLP-1RA semaglutide as an add-on therapy to insulin for overweight/obese adult patients with CFRD.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Amir Moheet

Lead Sponsor

Trials

2

Recruited

20+

Cystic Fibrosis Foundation

Collaborator

Trials

199

Recruited

37,800+

Published Research Related to This Trial

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a patient with cystic fibrosis-related diabetes (CFRD), adding semaglutide, a GLP-1 receptor agonist, to basal insulin significantly improved glycemic control, reducing HbA1c from 9.1% to 6.7% within 3 months.

The treatment did not lead to any increase in plasma pancreatic enzyme concentrations, indicating a safe profile for semaglutide when used in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide in Cystic Fibrosis-Related Diabetes. Gnanapragasam, H., Mustafa, N., Bierbrauer, M., et al.[2022]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

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]

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]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

In a 52-week study involving 731 patients with type 2 diabetes, oral semaglutide significantly reduced HbA1c levels and body weight compared to placebo, demonstrating its efficacy when added to insulin with or without metformin.

The most common side effect of oral semaglutide was nausea, which was mostly mild to moderate, indicating a safety profile similar to other glucagon-like peptide 1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Zinman, B., Aroda, VR., Buse, JB., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10915598/

The Changing Landscape of Treatment for Cystic Fibrosis ... Patients with Cystic Fibrosis related diabetes [CFRD] are treated with insulin and high calorie diets to maintain body mass.

2. sciencedirect.com sciencedirect.com/science/article/pii/S3050915725000189

Glucagon-Like Peptide 1 Agonist Use in an Adult With ... All individuals lost weight (mean, −7.2 kg), and 8 individuals showed improvement in percent predicted forced expiratory volume in 1 second. In the 7 ...

3. liebertpub.com liebertpub.com/doi/full/10.1089/dia.2024.0367

GLP-1 Receptor Agonist Therapy in Cystic Fibrosis- ... Significant improvement in glycemic control and weight loss were observed in this patient, leading to complete discontinuation of insulin therapy. While these ...

4. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16516?af=R

Glucagon‐like peptide‐1 receptor agonists in adults with ... Early initiation of insulin therapy has been linked to improved nutritional outcomes and may potentially stabilize pulmonary function by ...

5. withpower.com withpower.com/trial/phase-2-and-3-cystic-fibrosis-3-2023-0f61a

Semaglutide for Cystic Fibrosis-Related Diabetes It helps lower blood sugar by increasing insulin release and also aids in weight loss. Although specific data for cystic fibrosis-related diabetes is limited, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05788965?tab=table

Researcher View | NCT05788965 | Semaglutide in CFRD Hypothesis 1: Weekly therapy with GLP-1RA semaglutide will be safe and well tolerated in overweight/obese adults with CFRD.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2214623724000462

Glucagon-like peptide1 receptor agonist treatment of cystic ... We report, for the first time, five cases of individuals with CFRD complicated by obesity treated with GLP 1-RA for at least two years.