SGLT2 Inhibitor for Type 1 Diabetes

(ACT T1D Trial)

Recruiting at 1 trial location

Overseen By Justin Gregory, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how an SGLT2 inhibitor, a medication that lowers blood sugar, can assist people with type 1 diabetes in managing insulin levels and improving heart and blood sugar health. The study also includes individuals with a rare form of diabetes known as GCK-MODY and healthy volunteers to enhance understanding of the results. Participants will receive varying insulin levels to simulate conditions for those with and without diabetes. Ideal participants are those who have had type 1 diabetes for 1 to 30 years and use automated insulin delivery systems. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

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

Research has shown that SGLT2 inhibitors, which help the body eliminate excess sugar through urine, have been studied for their safety. They are known to reduce the risk of serious heart problems, such as heart attacks and strokes. Studies also suggest that these drugs might benefit people with kidney issues and have a good safety record.

However, there is a risk of diabetic ketoacidosis (DKA), a serious condition where the body produces too much acid in the blood. This risk increases for people using SGLT2 inhibitors, especially those with type 1 diabetes. Monitoring for any unusual symptoms is important.

Overall, many people tolerate these drugs well, but they come with some risks that require careful management. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Type 1 Diabetes focus on managing blood sugar levels through insulin therapy. However, the SGLT2 inhibitor offers a different approach by targeting the kidneys to prevent glucose reabsorption, thus lowering blood sugar levels without relying solely on insulin. Researchers are excited about this treatment because it has the potential to improve blood sugar control and reduce the risk of complications linked to insulin resistance. Additionally, it may offer benefits for cardiovascular health, which is a major concern for people with diabetes.

What evidence suggests that this SGLT2 inhibitor might be an effective treatment for type 1 diabetes?

Studies have shown that SGLT2 inhibitors effectively lower blood sugar levels by helping the body remove excess sugar through urine. Research indicates these medications also benefit heart health by reducing the risk of heart problems. In people with diabetes, evidence suggests SGLT2 inhibitors can lower the risk of worsening kidney disease. Although limited data exist on SGLT2 inhibitors for type 1 diabetes, they have shown promise in managing insulin levels and improving heart health. This trial will explore the effects of SGLT2 inhibitors on insulin management and cardiovascular health in type 1 diabetes. Early findings suggest these drugs may reduce the body's need for insulin, potentially improving heart and blood vessel function. ^{1 4 6 7 8}

Who Is on the Research Team?

Justin Gregory, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK576405/

Sodium-Glucose Transport 2 (SGLT2) Inhibitors - NCBI - NIH Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, have transformed ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/article-abstract/2829196

Comparative Effectiveness of Individual Sodium-Glucose ... This study found that individual SGLT-2 inhibitors demonstrated comparable cardiovascular effectiveness at clinically effective doses.

3. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(22)02074-8/fulltext

collaborative meta-analysis of large placebo-controlled trials Overall, SGLT2 inhibitors reduced the risk of kidney disease progression and the composite of cardiovascular death or hospitalisation for heart ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.031805

A Network Meta‐Analysis of Randomized Controlled Trials In the overall cohort, there were no significant differences in the primary efficacy outcome among the SGLT2 inhibitors, while empagliflozin ( ...

5. diabetesjournals.org diabetesjournals.org/care/article/43/1/90/35940/Use-of-Sodium-Glucose-Cotransporter-2-Inhibitors

Use of Sodium–Glucose Cotransporter 2 Inhibitors in Patients ... Among 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in ...

6. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16385

A review of the safety of sodium‐glucose co‐transporter‐2 ... SGLT2 inhibitors reduce the risk of major adverse cardiovascular events (MACE; consisting of cardiovascular death, nonfatal stroke or nonfatal myocardial ...

7. nature.com nature.com/articles/s41598-025-86172-y

Real-world effectiveness and safety of sodium-glucose co ... These findings suggest SGLT2i therapy might reduce adverse kidney outcomes in CKD patients, regardless of diabetic status, with a favorable safety profile.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39602586/

A Systematic Review and Meta-analysis on the Safety and ... SGLT2 inhibitor use among hospitalized patients was associated with numerically higher rates of ketoacidosis, although further studies are required.