SGLT2 Inhibitor for Type 1 Diabetes

(ACT T1D Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Insulin

Must not be taking: Antioxidants, Antipsychotics, Beta blockers, others

Disqualifiers: Severe hypoglycemia, Hypertension, Kidney disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

Duration: 5 hours

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including antioxidant vitamins, systemic glucocorticoids, antipsychotics, specific beta-blockers, niacin, thiazide diuretics, certain oral contraceptives, growth hormone, immunosuppressants, antihypertensives, and antihyperlipidemics. If you are taking any of these, you may need to stop before joining the trial.

What data supports the effectiveness of the drug SGLT2 Inhibitor for Type 1 Diabetes?

Research shows that SGLT2 inhibitors, when used alongside insulin, can help manage blood sugar levels in people with type 1 diabetes, although their safety and effectiveness can vary. ^{1 2 3 4 5}

What is known about the safety of SGLT2 inhibitors in humans?

SGLT2 inhibitors have been studied for safety in both type 1 and type 2 diabetes. They can cause side effects like ketoacidosis (a serious condition where the body produces too many acids), genital infections, and dehydration, but they are generally considered safe for many people. ^{1 6 7 8 9}

How is the SGLT2 inhibitor drug different for treating type 1 diabetes?

SGLT2 inhibitors are unique because they help lower blood sugar by preventing the kidneys from reabsorbing glucose, which is different from most other diabetes treatments that focus on insulin. This makes them potentially useful for type 1 diabetes, even though they were originally developed for type 2 diabetes. ^{6 8 10 11 12}

What is the purpose of this trial?

This study aims to understand the heart and blood sugar health benefits of using an adjunctive therapy to lower high insulin levels in people with type 1 diabetes. The investigators will also look at people with a specific type of diabetes called Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY) and those without diabetes to help interpret the results. The investigators will use a medication that helps the body get rid of sugar, called and SGLT2 inhibitor, with the goal to reduce the body's insulin requirements. The investigators believe this could lead to better heart and blood sugar health, including a better response to insulin and more available nitric oxide, a gas that helps blood vessels function well. The investigators will compare heart and blood sugar health risk factors in participants with type 1 diabetes, participants with Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), and non-diabetic healthy volunteers under two conditions: high insulin levels typical of type 1 diabetes and normal insulin levels typical of the other two groups.

Eligibility Criteria

This trial is for people with type 1 diabetes to explore the benefits of reducing high insulin levels using an SGLT2 inhibitor, a drug that helps eliminate sugar from the body. It also includes individuals with GCK-MODY and healthy subjects to compare results.

Inclusion Criteria

I weigh 50 kg or more.

My HbA1c levels are between 5.7% and 7.5%.

BMI: 18-28 kg/m²

Exclusion Criteria

My blood pressure is higher than 140/100 mmHg.

I have not been hospitalized for diabetic ketoacidosis in the last 6 months.

I am currently taking Niacin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a high insulin infusion or a normal insulin infusion to assess insulin resistance and endothelial function

5 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

Trial Overview The study tests if an SGLT2 inhibitor can improve heart health and blood sugar management in type 1 diabetics by lowering their need for insulin. Participants will be compared under conditions of high and normal insulin levels.

Participant Groups

Group I: High insulin Experimental Treatment 3 Interventions

Participants will receive a "high insulin infusion" (Hi-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to patients with type 1 diabetes for five hours.

Group II: Normal insulin Active Control 4 Interventions

Participants will receive a "normal insulin infusion" (Eu-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to people without diabetes and people with GCK-MODY for five hours.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

SGLT2 inhibitors significantly lower key diabetes markers in type 1 diabetes patients, including glycated hemoglobin (HbA1c) and fasting plasma glucose, while also reducing body weight and total insulin dosage, based on a meta-analysis of 16 randomized controlled trials involving 7192 patients.

Importantly, the use of SGLT2 inhibitors does not increase the risk of hypoglycemia, urinary tract infections, or diarrhea, suggesting they can be safely integrated into treatment regimens for type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials. Nan, J., Wang, D., Zhong, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials. [2023]

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

SGLT-2 Inhibitors: Is There a Role in Type 1 Diabetes Mellitus Management? [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Sodium-glucose cotransporter 2 inhibitors as an add-on therapy to insulin for type 1 diabetes mellitus: Meta-analysis of randomized controlled trials. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Safety and efficacy of sodium glucose co-transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta-analysis of randomized controlled trials. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of sodium-glucose co-transporter-2 inhibitors for treating patients with type 1 diabetes. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 1 diabetes: A systematic review and meta-analysis. [2022]

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

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. [2023]

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

Elements for Success in Managing Type 2 Diabetes With SGLT-2 Inhibitors: Overview of the Efficacy and Safety of SGLT-2 Inhibitors in Type 2 Diabetes Mellitus. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. [2013]

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

The potential role of sodium glucose co-transporter 2 inhibitors in combination therapy for type 2 diabetes mellitus. [2022]

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

Benefits of SGLT2 Inhibitors Beyond Glycemic Control - A Focus on Metabolic, Cardiovascular and Renal Outcomes. [2022]