GLP-1 for Type 1 Diabetes

Overseen By Maka Siamashvili, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Anticoagulants, Antidepressants, Antipsychotics, others

Disqualifiers: Pregnancy, Hypertension, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including non-selective beta blockers, sedative-hypnotics, anticonvulsants, antiparkinsonian drugs, antipsychotics, antidepressants, mood stabilizers, CNS stimulants, opioids, and hallucinogens.

What data supports the effectiveness of GLP-1 drugs for type 1 diabetes?

GLP-1 drugs, which are effective in lowering blood sugar levels in type 2 diabetes, are being explored for type 1 diabetes as well. They help control blood sugar by mimicking a natural hormone that regulates glucose, and studies are looking into their safety and effectiveness in real-life settings for type 1 diabetes. ^{1 2 3 4 5}

Is GLP-1 safe for humans?

GLP-1 receptor agonists are generally considered safe, with a low risk of causing low blood sugar. The most common side effect is nausea, which usually goes away after starting treatment. There are some concerns about potential effects on the thyroid and a possible link to pancreatitis and cancer, but these are still being studied. ^{6 7 8 9 10}

How is the drug GLP-1 different from other treatments for type 1 diabetes?

GLP-1 drugs are unique because they help control blood sugar without causing low blood sugar (hypoglycemia) and can also help with weight management, unlike traditional insulin treatments. They work by mimicking a natural hormone that stimulates insulin production and reduces appetite, offering a novel approach for managing type 1 diabetes. ^{1 11 12 13 14}

What is the purpose of this trial?

The hypotheses to be tested in this application is: GLP-1 will acutely protect arterial endothelial function and reduce pro-atherothrombotic and pro-coagulant effects of repeated hypoglycemia in T1DM.

Eligibility Criteria

This trial is for adults aged 18-50 with Type 1 Diabetes, a BMI under 40kg/m2, and HbA1c levels below 11.0%. Participants should not have diabetic complications like retinopathy or neuropathy. They must not be pregnant, have significant heart issues, severe liver or kidney problems, anemia, or be on certain medications like beta blockers or anticoagulants.

Inclusion Criteria

Your body mass index is less than 40.

Your HbA1c level is below 11.0%.

I do not have complications from diabetes like eye or nerve problems.

Exclusion Criteria

I am unable or unwilling to follow the required contraception guidelines.

I have recently had a stroke or brain injury.

Your liver function tests show levels of SGOT and SGPT that are more than twice the normal range.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GLP-1 or placebo infusion during episodes of hypoglycemia

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Glucagon-like peptide-1
• Placebos

Trial Overview The study tests if Glucagon-like peptide-1 (GLP-1) can protect blood vessel function and reduce the risk of blood clots after low blood sugar events in people with Type 1 Diabetes. Some participants will receive GLP-1 while others will get a placebo to compare effects.

Participant Groups

Group I: GLP-1 Experimental Treatment 1 Intervention

The participants will be randomized to Glucagon-like peptide-1 infusion.

Group II: Placebo 1 Placebo Group 1 Intervention

The participants will be randomized to placebo infusion.

Group III: Placebo 2 Placebo Group 1 Intervention

The participants will be randomized to placebo infusion.

Glucagon-like peptide-1 is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as GLP-1 analogs for:

• Type 2 diabetes
• Obesity

Approved in United States as GLP-1 receptor agonists for:

• Type 2 diabetes
• Obesity
• Cardiovascular risk reduction

Approved in Canada as GLP-1 analogs for:

• Type 2 diabetes
• Obesity

Approved in Japan as GLP-1 receptor agonists for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

GLP-1 agonists, particularly liraglutide, can help lower hemoglobin A1C levels in patients with type 1 diabetes, although the reduction is modest and not significantly different from control groups, with a maximum decrease of 0.6%.

These medications are associated with weight loss (up to 6.4 kg over 24 weeks) and have a low incidence of hypoglycemia compared to insulin therapy, but gastrointestinal side effects like nausea may limit their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 Agonists in Type 1 Diabetes Mellitus. Janzen, KM., Steuber, TD., Nisly, SA.[2022]

In a study of 11 patients with type 1 diabetes using liraglutide, significant improvements were observed after 10 weeks, including a 4.2% reduction in body weight and a 19.2% decrease in total daily insulin dose, alongside a reduction in Hemoglobin A1c levels from 7.4% to 7.0%.

The addition of liraglutide to insulin therapy did not increase the risk of hypoglycemia, although nausea was a common side effect, leading to discontinuation in 4 out of 11 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs. Harrison, LB., Mora, PF., Clark, GO., et al.[2016]

Incretin mimetics, particularly GLP-1 receptor agonists, are a promising new treatment for type 2 diabetes, leveraging the natural hormone GLP-1 to improve glycemic control and counteract diabetes-related issues.

Currently marketed GLP-1 analogues like exenatide and liraglutide require daily dosing, but new formulations in development aim for once-weekly dosing, potentially enhancing patient compliance and overall treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly GLP-1 agonists: How do they differ from exenatide and liraglutide? Christensen, M., Knop, FK.[2022]

GLP-1 is an important hormone for managing type 2 diabetes because it lowers blood sugar, reduces glucagon secretion, and slows down how quickly food leaves the stomach.

New GLP-1 agonists are being developed that not only improve blood sugar control but also aim for greater weight loss, combining GLP-1 receptor activation with other innovative mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Type 2 Diabetes Mellitus: What's Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline? Elder, MJ., Ashjian, EJ.[2023]

GLP-1 receptor agonists, such as liraglutide and dulaglutide, effectively lower blood sugar levels in type 2 diabetes patients, reducing A1C by approximately 0.8-1.6% and promoting weight loss of about 1-3 kg.

These medications have a low risk of causing hypoglycemia and primarily lead to gastrointestinal side effects, making them a safe option when patients are properly selected and educated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes. Hinnen, D.[2023]

A review of 120 cases of adverse drug reactions (ADRs) associated with GLP-1 agonists in type 2 diabetes patients revealed that gastrointestinal disorders, especially pancreatitis, were the most frequently reported issues.

Liraglutide and exenatide were found to be the GLP-1 agonists most commonly linked to these adverse reactions, highlighting the need for careful monitoring of patients using these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of GLP-1 agonists: A systematic review of case reports. Shetty, R., Basheer, FT., Poojari, PG., et al.[2022]

GLP-1 receptor agonists, while raising safety concerns about potential links to pancreatitis and tumors, have not shown a significant association with these risks in clinical studies, which often have biases.

Regulatory bodies like the FDA and EMA suggest that current safety concerns should not hinder the use of GLP-1Rx agonists, as they provide important benefits for many patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential side effects to GLP-1 agonists: understanding their safety and tolerability. Consoli, A., Formoso, G.[2018]

Liraglutide, a GLP-1 analog, effectively reduces hemoglobin A1c levels and body weight in patients with type 2 diabetes, with a low risk of hypoglycemia when used alone, based on data from large clinical trials.

The once-daily dosing of liraglutide may offer advantages over other treatments like exenatide, as it maintains similar efficacy while being more convenient for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus. Neumiller, JJ., Campbell, RK.[2022]

GLP-1 receptor agonists (GLP-1ra) effectively lower blood sugar levels with a low risk of hypoglycemia, making them a safe option for diabetes management.

The most common side effect is transient nausea, affecting 20-60% of patients at the beginning of treatment, while concerns about potential links to pancreatitis and cancer are still under investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of GLP-1 receptor agonists]. Soldevila, B., Puig-Domingo, M.[2018]

GLP-1 receptor agonists (GLP-1ra) effectively lower blood sugar levels with a low risk of hypoglycemia, making them a safe option for diabetes treatment.

The most common side effect is transient nausea, affecting 20-60% of patients at the beginning of treatment, while concerns about potential links to pancreatitis and cancer are still debated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of GLP-1 receptor agonists]. Soldevila, B., Puig-Domingo, M.[2015]

Exenatide, a GLP-1 receptor agonist, effectively improved glycemic control and reduced body mass in rat models of obesity induced by both hypothalamic injury and high-calorie diet, demonstrating its potential as an antidiabetogenic treatment.

While exenatide showed benefits in managing diabetes in both models, it was specifically anti-obesogenic and hypolipidemic only in the diet-induced obesity model, suggesting its effectiveness may depend on the underlying cause of obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-obesogenic and hypolipidemic effects of a glucagon-like peptide-1 receptor agonist derived from the saliva of the Gila monster. Alves, PL., Abdalla, FMF., Alponti, RF., et al.[2018]

GLP-1 analogues, such as exenatide and liraglutide, significantly improve glycemic control in type 2 diabetes patients, reducing HbA1c levels by about 1% compared to placebo, based on a review of 17 trials with 6899 participants.

These medications also promote weight loss and improve beta-cell function, although gastrointestinal side effects like nausea are common, particularly at the start of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus. Shyangdan, DS., Royle, P., Clar, C., et al.[2023]

GLP-1 mimetics are promising alternatives to insulin for diabetes treatment, as they do not cause hypoglycemia and can help prevent weight gain, making them valuable in therapy development.

Recent advancements focus on creating non-fusion GLP-1 analogues with longer half-lives that are more suitable for oral administration, addressing the challenge of the short half-lives of traditional GLP-1 treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in GLP-1 Receptor Agonists for Use in Diabetes Mellitus. McBrayer, DN., Tal-Gan, Y.[2018]

GLP-1 is a powerful hormone that lowers blood glucose levels by stimulating insulin production and secretion from pancreatic beta-cells, making it a promising treatment for type 2 diabetes.

Synthetic analogs of GLP-1, such as NN2211 and Exendin-4, have been developed to enhance its therapeutic effects by prolonging its action and improving its stability in the body, which could lead to better management of diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus. Holz, GG., Chepurny, OG.[2019]

References

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

GLP-1 Agonists in Type 1 Diabetes Mellitus. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs. [2016]

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

Once-weekly GLP-1 agonists: How do they differ from exenatide and liraglutide? [2022]

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

Pharmacotherapy for Type 2 Diabetes Mellitus: What's Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline? [2023]

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

Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of GLP-1 agonists: A systematic review of case reports. [2022]

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

Potential side effects to GLP-1 agonists: understanding their safety and tolerability. [2018]

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

Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of GLP-1 receptor agonists]. [2018]

10. Spain pubmed.ncbi.nlm.nih.gov

[Safety and tolerability of GLP-1 receptor agonists]. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Anti-obesogenic and hypolipidemic effects of a glucagon-like peptide-1 receptor agonist derived from the saliva of the Gila monster. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus. [2023]

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

Recent Advances in GLP-1 Receptor Agonists for Use in Diabetes Mellitus. [2018]

14. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus. [2019]