SGLT2 Inhibitor for Cystic Fibrosis-related Diabetes

Overseen By Amir Moheet, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Minnesota

Must be taking: Insulin

Must not be taking: Glucocorticoids

Disqualifiers: Type 1 diabetes, Pregnancy, Chronic liver disease, Chronic kidney disease, others

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: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called empagliflozin (an SGLT2 inhibitor) to determine its safety and tolerability for individuals with cystic fibrosis-related diabetes (CFRD) who are overweight or obese. The study compares the effects of empagliflozin to a placebo, with participants randomly assigned to one or the other for four weeks. It aims to gather early data to support a larger future study. Suitable candidates for this trial include those with CFRD who are on insulin treatment and have a body mass index (BMI) over 25. As a Phase 2 trial, this study measures how well empagliflozin works in an initial, smaller group, offering participants a chance to contribute to important early research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but there is a 4-week washout period (time without taking certain medications) mentioned. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that empagliflozin, an SGLT2 inhibitor, is being tested for safety and effectiveness in people with cystic fibrosis-related diabetes (CFRD). In a small study with eight CFRD patients, some who used SGLT2 inhibitors like empagliflozin along with insulin for one year experienced a decrease in body mass index (BMI), suggesting the treatment was generally well-tolerated during this period.

While detailed safety information specifically for empagliflozin in CFRD is not available from these studies, SGLT2 inhibitors are generally considered safe. The FDA has already approved empagliflozin for treating type 2 diabetes, providing some reassurance about its safety. The current clinical trial is in an advanced stage, indicating that earlier studies have deemed the treatment safe enough for further testing.

As with any medication, side effects can occur, but the trial is designed to closely monitor and evaluate these. Participants in the study will contribute valuable information on how well empagliflozin is tolerated by people with CFRD. ^{1 2 3 4 5}

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

Unlike the standard treatments for cystic fibrosis-related diabetes, which often include insulin therapy to manage blood sugar levels, empagliflozin offers a unique approach by targeting the kidneys. As an SGLT2 inhibitor, empagliflozin works differently by helping the kidneys remove excess glucose from the body through urine, potentially offering better control of blood sugar levels without the need for insulin. Researchers are excited about empagliflozin because it not only provides a novel mechanism of action but also may improve overall metabolic health and reduce the burden of managing diabetes in cystic fibrosis patients.

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

In this trial, participants will be randomized to receive either empagliflozin or a placebo control. Research has shown that empagliflozin, a type of medication, may help control blood sugar levels in people with cystic fibrosis-related diabetes (CFRD). One study found that patients using this medication improved their body mass index (BMI), suggesting it might aid in weight management and diabetes control. While empagliflozin is mainly known for reducing heart risks in type 2 diabetes, it seems promising for CFRD because it helps the kidneys remove extra sugar from the body. Early findings suggest it is safe and well-tolerated in people with CFRD who are overweight or obese. Further research is underway to confirm its effectiveness specifically for CFRD. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for overweight or obese adults (BMI >25) aged 18+ with Cystic Fibrosis-related Diabetes (CFRD) who are on insulin. Participants capable of pregnancy must use effective contraception. Excluded are those with recent severe lung issues, chronic kidney disease, organ transplants, non-English speakers, new CFTR therapy users within 12 weeks, Type 1 diabetes patients, and individuals with a history of certain infections or eating disorders.

Inclusion Criteria

A participant who is capable of becoming pregnant must agree to take precautions that are effective in preventing pregnancy throughout this study. These methods could include one of the following: 1. Complete abstinence from sexual intercourse; 2. Tubal ligation; 3. Use combination of two forms of contraception during the study including, oral, injectable, or implanted hormonal contraceptives, intrauterine device or barrier method.

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

You are allergic to empagliflozin or any ingredients in Jardiance.

You have a history of an eating disorder.

I started a new CFTR therapy less than 12 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either empagliflozin or placebo for 4 weeks

4 weeks

4 visits (in-person)

Washout

Participants undergo a 4-week washout period between treatment phases

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Placebo Control

Trial Overview The study tests the safety and effectiveness of Empagliflozin in CFRD patients compared to a placebo. It's designed as a double-blind crossover study—meaning participants will receive both the drug and placebo at different times without knowing which one they're taking—with a break period between treatments.

How Is the Trial Designed?

Group I: empagliflozin Active Control 1 Intervention

randomized to study medication (empagliflozin) 10 mg taken by mouth daily for 4 weeks

Group II: placebo control Placebo Group 1 Intervention

randomized to placebo control taken by mouth daily for 4 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?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Amir Moheet

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

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]

Empagliflozin (Jardiance) is a new medication classified as an SGLT2 inhibitor, specifically designed to help manage blood sugar levels in individuals with type-2 diabetes.

This medication not only aids in lowering blood glucose but also has potential benefits for heart health, making it a promising option for patients with diabetes at risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. Ndefo, UA., Anidiobi, NO., Basheer, E., et al.[2020]

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 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 (Jardiance) is an effective once-daily treatment for type 2 diabetes that works by inhibiting glucose reabsorption in the kidneys, leading to improved blood sugar control, weight loss, and reduced blood pressure, as shown in phase III trials lasting up to 104 weeks.

In a large trial, empagliflozin was found to be noninferior to glimepiride and even superior at 104 weeks in lowering glycated hemoglobin levels, with a good safety profile and minimal risk of hypoglycemia, especially when not used with insulin or sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: a review of its use in patients with type 2 diabetes mellitus. Scott, LJ.[2021]

Empagliflozin is an effective oral medication for type 2 diabetes that works independently of insulin, showing improvements in blood glucose levels, body weight, and blood pressure across various patient populations.

It has been found to be well tolerated with no increased risk of hypoglycemia compared to placebo, making it a safe option for managing diabetes either alone or in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. White, JR.[2018]

In a 3-year study involving 362 patients with type 2 diabetes, both empagliflozin and dapagliflozin effectively improved glycemic control, with empagliflozin showing a greater reduction in HbA1c (-1.7%) compared to dapagliflozin (-1.1%).

Empagliflozin also led to a more significant weight loss (-4.5 kg) compared to dapagliflozin (-1.0 kg), while both medications had similar safety profiles with no significant differences in adverse events or cardiovascular outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study. Ku, EJ., Lee, DH., Jeon, HJ., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12264597/

SGLT2 inhibitor therapy in overweight and obese patients with ... This case series presents eight CFRD patients treated with SGLT2 inhibitors alongside insulin for one year. Half had BMI reductions (1.33–2.89 kg/m2); others ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06149793

SGLT2 Inhibitor Therapy in Cystic Fibrosis-related Diabetes We hypothesize that empagliflozin will be safe, well tolerated and will improve glycemic control in overweight/obese adult patients with CFRD. Specific Aim 1: ...

3. withpower.com withpower.com/trial/phase-2-and-3-cystic-fibrosis-11-2023-86d3f

SGLT2 Inhibitor for Cystic Fibrosis-related Diabetes Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established ...

4. app.trialscreen.org app.trialscreen.org/trials/phase-2-3-efficacy-safety-sglt2-inhibitor-therapy-overweight-obese-subjects-trial-nct06149793

SGLT2 Inhibitor Therapy in Cystic Fibrosis-related Diabetes A study to evaluate the safety and effectiveness of empagliflozin in overweight/obese adults with cystic fibrosis-related diabetes. Check your eligibility

5. pharmacytimes.com pharmacytimes.com/view/jardiance-reduces-cardiovascular-death-in-type-2-diabetes

Jardiance Reduces Cardiovascular Death in Type 2 Diabetes The FDA recently approved empagliflozin (Jardiance) to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and cardiovascular ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1499267124001783

Cystic Fibrosis–related Diabetes: A First Canadian Clinical ... Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: Results of the cystic fibrosis related diabetes therapy trial.