Empagliflozin for Type 1 Diabetes

Recruiting at 1 trial location

Overseen By Adelyn Moore

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must be taking: Insulin

Must not be taking: GLP1 agonists, Glucocorticoids

Disqualifiers: Pregnancy, Breastfeeding, Severe hypoglycemia, 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: 26 weeks

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether daily empagliflozin can help individuals with type 1 diabetes better control their blood sugar when used with an automated insulin delivery (AID) system. The main goal is to determine if this combination allows more time with blood sugar in a healthy range compared to a placebo. Individuals who have had type 1 diabetes for at least a year, use an AID system, and still struggle to maintain their blood sugar in the recommended range might be suitable for this trial. Participants will take either empagliflozin or a placebo for 26 weeks. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how it can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that participants do not use any anti-hyperglycemic agents other than insulin within 2 weeks before starting, and no GLP1-Receptor Agonists or high doses of glucocorticoids within 1 month before starting. If you are on these medications, you may need to stop them before joining the trial.

What is the safety track record for empagliflozin?

Research shows that empagliflozin is generally safe for people. Studies have found it does not increase the risk of severe low blood sugar, bone fractures, or lower limb amputations. When added to insulin treatment for type 1 diabetes, empagliflozin helped control blood sugar and manage weight without raising the risk of low blood sugar.

However, the risk of ketoacidosis (a condition where acids build up in the blood) remains similar whether or not empagliflozin is taken. While empagliflozin is safe for most people, it is important to be aware of potential risks and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for Type 1 diabetes focus on insulin replacement or injection. However, empagliflozin works differently by targeting the kidneys. It is a sodium/glucose cotransporter 2 inhibitor (SGLT2i) that helps prevent glucose from being reabsorbed in the kidneys, which can help lower blood sugar levels. Researchers are excited about this treatment because it offers a new approach to managing blood sugar levels, potentially improving overall glucose control when used alongside insulin therapy.

What evidence suggests that empagliflozin might be an effective treatment for type 1 diabetes?

Research has shown that empagliflozin can help people with type 1 diabetes manage their blood sugar levels more effectively. In earlier studies, patients using empagliflozin with insulin achieved better blood sugar control and required less insulin. These studies also found no increased risk of low blood sugar with empagliflozin. Although typically used for type 2 diabetes, its potential benefits for type 1 diabetes are under investigation in this trial. Participants will receive either empagliflozin or a placebo to evaluate its effectiveness in managing blood sugar. ^{2 4 6 7 8}

Who Is on the Research Team?

Melissa-Rosina Pasqua, MD

Principal Investigator

Research Institute of the McGill University Health Centre

Are You a Good Fit for This Trial?

Adults over 18 with type 1 diabetes for at least a year, using an automated insulin delivery system for 3+ months but not meeting glucose control targets. They must agree to effective birth control if of child-bearing age.

Inclusion Criteria

I agree to use effective birth control and avoid pregnancy during the trial.

I have used an advanced AID system for at least 3 months.

Time in range (3.9 to 10.0 mmol/L) < 70% on their personal AID system in the 30 days prior to screening (with minimum 70% time spent in closed-loop mode)

Exclusion Criteria

Breastfeeding

I have been taking high doses of steroids for the last month or less.

I have had a severe low blood sugar episode that caused a seizure, unconsciousness, or an ER visit in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 2.5 mg of empagliflozin or a placebo daily for 26 weeks while using their automated insulin delivery system

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The trial is testing whether adding Empagliflozin (2.5 mg daily) to current AID systems helps adults with type 1 diabetes stay within their target blood sugar range better than a placebo does over a period of 26 weeks.

How Is the Trial Designed?

Group I: Empagliflozin 2.5 mg daily Experimental Treatment 1 Intervention

Empagliflozin is a sodium/glucose cotransporter 2 inhibitor (SGLT2i) that inhibits glucose reabsorption in the kidney. In this study, a capsule of empagliflozin 2.5 mg will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.

Group II: Placebo Active Control 1 Intervention

As a control, a placebo capsule will be taken daily in conjunction with the participant's personal automated insulin delivery system for 26 weeks.

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Diabetes Canada

Collaborator

Trials

13

Recruited

1,200+

Published Research Related to This Trial

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

Empagliflozin, an SGLT2 inhibitor, is effective in managing blood glucose levels and reducing cardiovascular risks in patients with type 2 diabetes, but it can also lead to euglycemic diabetic ketoacidosis under certain conditions, such as acute illness or reduced carbohydrate intake.

A case study of a 23-year-old female with poorly controlled diabetes on empagliflozin revealed severe euglycemic metabolic acidosis and elevated urine ketones during a COVID-19 infection, highlighting the need for careful monitoring in patients using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Severe Metabolic Acidosis due to Jardiance-Induced Euglycemic Diabetic Ketoacidosis. Dyatlova, N., Omotosho, YB., Sherchan, R., et al.[2021]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

Empagliflozin, an SGLT2 inhibitor, is effective in improving blood sugar control in adults with type 2 diabetes, especially when metformin is not suitable.

In addition to managing diabetes, empagliflozin also aims to reduce cardiovascular risks associated with the condition, highlighting its dual role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873775/

The effects of empagliflozin in patients with type 1 diabetes In this trial, empagliflozin 10 mg treatment for 12 weeks improved glycemic control and reduced total daily insulin doses and BMI in patients with T1D. The ...

2. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/t2d/efficacy

T2D Efficacy Data | Jardiance® (empagliflozin) tablets JARDIANCE is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase their risk of diabetic ketoacidosis.

3. diabetesjournals.org diabetesjournals.org/care/article/41/12/2560/36495/Empagliflozin-as-Adjunctive-to-Insulin-Therapy-in

Empagliflozin as Adjunctive to Insulin Therapy in Type 1 ... Empagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6709813/

Empagliflozin in type 1 diabetes - PMC In addition, treatment with empagliflozin resulted in a placebo-corrected reduction in body weight (up to −3.4 kg), systolic blood pressure (up ...

5. journals.lww.com journals.lww.com/cjasn/fulltext/2021/11000/kidney_effects_of_empagliflozin_in_people_with.14.aspx

Kidney Effects of Empagliflozin in People with Type 1... Similar to observations in type 2 diabetes, in the pooled analysis in participants with baseline UACR ≥30 mg/g, UACR decreased by 55% with empagliflozin 25 mg ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213770/

Safety of Empagliflozin: An Individual Participant-Level ... Empagliflozin was not associated with an increased incidence of severe hypoglycemia, bone fractures, or lower limb amputations. Empagliflozin is ...

7. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/jardiance-empagliflozin-analysis-reinforces-established-safety-profile

Jardiance® (empagliflozin) T2D Analysis on Safety Profile The landmark EMPA-REG OUTCOME trial demonstrated that Jardiance reduced the risk of cardiovascular death by 38 percent versus placebo in people ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/jcpt.13521

Efficacy and safety of empagliflozin at different doses in ... High-daily doses (10, 25, 50 mg) had better efficacy than low doses (1, 2.5, 5 mg). When considering HbA1c, FPG and total AEs, 25 mg performed best among the ...