Ertugliflozin for Sleep Apnea

(ADIPOSA Trial)

Recruiting at 1 trial location

Overseen By Henry K Yaggi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must not be taking: Sleep-inducing, SGLT2i, GLP-1 agonists, UGT inducers

Disqualifiers: Type 1 diabetes, Severe liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug ertugliflozin (Steglatro) can reduce the severity of sleep apnea in overweight or obese individuals with moderate to severe obstructive sleep apnea (OSA). Participants will receive either the drug or a placebo (a non-active look-alike substance) for six months, alongside their regular care. The trial aims to determine if improvements in sleep apnea symptoms correlate with changes in body traits and functions. Individuals who are overweight or obese and have been diagnosed with OSA might be suitable candidates for this trial. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take sleep-inducing medications, SGLT2 inhibitors, GLP-1 receptor agonists, or UGT inducers during the study.

What is the safety track record for these treatments?

Research has shown that bexagliflozin is generally safe and effective for treating type 2 diabetes. It might also help with other conditions, such as sleep apnea, which is currently under study. Studies have found that bexagliflozin is well-tolerated when used alone or with other diabetes treatments, and no major safety concerns have been reported.

Most side effects were mild. Common ones included urinary tract infections and increased urination, as the drug helps remove extra sugar through urine. Since bexagliflozin is in the late stages of research, strong evidence supports its safety. However, its safety for sleep apnea remains under investigation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for sleep apnea, which often involve devices like CPAP machines or lifestyle changes, Ertugliflozin is an oral medication that targets the condition in a new way. It works as a sodium-glucose co-transporter 2 (SGLT2) inhibitor, which is typically used to manage blood sugar levels in diabetes. Researchers are excited because Ertugliflozin could offer a simpler, pill-based option for sleep apnea, potentially improving symptoms by addressing underlying metabolic factors. This approach is particularly promising for patients who have difficulty adhering to current device-based treatments.

What evidence suggests that this trial's treatments could be effective for sleep apnea?

Research has shown that ertugliflozin might reduce the risk of developing obstructive sleep apnea (OSA). In the VERTIS CV study, participants taking ertugliflozin experienced about half as many new OSA cases compared to those not taking the drug. This finding suggests that ertugliflozin could alleviate some sleep apnea symptoms. The drug aids the body in eliminating excess sugar through urine, leading to weight loss, which might contribute to the improvement in sleep apnea symptoms. Although ertugliflozin primarily manages blood sugar in people with type 2 diabetes, it shows promise for OSA. Participants in this trial will receive either Bexagliflozin or a placebo to further investigate these effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Henry K Yaggi, M.D.

Principal Investigator

Yale University

Ian J Neeland, M.D.

Principal Investigator

Case Western Reserve University School of Medicine

Are You a Good Fit for This Trial?

The ADIPOSA study is for overweight or obese adults with moderate to severe obstructive sleep apnea (OSA). Participants must be able to consent, follow the study plan for 6 months, and have a confirmed OSA diagnosis. Excluded are those planning certain weight loss treatments, with hypersensitivity to the drug tested, pregnant women, users of sleep-inducing meds, and individuals with specific medical conditions or inability to undergo MRI.

Inclusion Criteria

Overweight or obese (body mass index 25-40 kg/m2)

I have been diagnosed with obstructive sleep apnea with an AHI or REI of 15 or more.

Able to provide informed consent and stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Currently or planning to follow a ketogenic diet pattern ('keto diet') prior to or during enrollment in the study

I have Type 1 diabetes.

I am not pregnant, breastfeeding, or planning to become pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either bexagliflozin or placebo once daily for 6 months, with routine clinical care

6 months

Baseline, 3 months, and 6 months visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ertugliflozin
• Placebo

Trial Overview This trial tests if Ertugliflozin can reduce the severity of sleep apnea in comparison to a placebo. It examines whether improvements in clinical measures of OSA result from changes in anatomic and physiologic traits. Participants will receive either the drug or placebo alongside routine care for six months while undergoing various clinical measurements.

How Is the Trial Designed?

Group I: Bexagliflozin Experimental Treatment 1 Intervention

Bexagliflozin once daily for 6 months

Group II: Placebo Placebo Group 1 Intervention

Placebo once daily for 6 months

Ertugliflozin is already approved in United States, European Union for the following indications:

Approved in United States as Steglatro for:

• Type 2 diabetes mellitus

Approved in European Union as Steglatro for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Published Research Related to This Trial

Dapagliflozin has been found to reduce the occurrence of central sleep apnea in patients diagnosed with this condition, which is significant as it may help avoid the need for more invasive ventilatory therapies.

This finding suggests that dapagliflozin could be a beneficial treatment option for managing central sleep apnea, potentially improving patient outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin initiation in chronic heart failure patients improves central sleep apnoea. Jaffuel, D., Bouchaut, Y., Mallet, JP., et al.[2023]

In a phase II study involving 328 patients with type 2 diabetes, ertugliflozin significantly reduced HbA1c levels, fasting plasma glucose, and body weight compared to placebo, demonstrating its efficacy in improving glycemic control.

Ertugliflozin was well tolerated with a low incidence of adverse events, including only 1.5% experiencing hypoglycemia, and showed no dose-related increase in adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin. Amin, NB., Wang, X., Jain, SM., et al.[2022]

In a 26-week phase III study involving 291 patients with type 2 diabetes, co-initiation of ertugliflozin and sitagliptin significantly reduced HbA1c levels compared to placebo, with reductions of -1.6% and -1.7% for the respective doses of ertugliflozin.

The combination treatment also led to significant improvements in fasting plasma glucose, body weight, and systolic blood pressure, while the safety profile was similar across all groups, with low incidences of specific adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study. Miller, S., Krumins, T., Zhou, H., et al.[2020]

In a study involving 8246 patients with type 2 diabetes and cardiovascular disease, the SGLT2 inhibitor ertugliflozin significantly reduced the incidence of obstructive sleep apnea (OSA) by 48% compared to placebo, with an incidence rate of 1.44 vs. 2.61 per 1000 person-years.

This exploratory analysis suggests that SGLT2 inhibitors like ertugliflozin may provide additional benefits beyond glucose control, potentially improving sleep-related health in patients with diabetes and cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial. Wojeck, BS., Inzucchi, SE., Neeland, IJ., et al.[2023]

Ertugliflozin effectively reduced HbA1c levels and improved fasting plasma glucose, body weight, and systolic blood pressure in adults with type 2 diabetes over a 104-week study, demonstrating sustained efficacy.

While ertugliflozin was well tolerated, it was associated with a higher incidence of female genital mycotic infections, but it also resulted in fewer cases of symptomatic hypoglycemia compared to placebo or glimepiride.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial. Gallo, S., Charbonnel, B., Goldman, A., et al.[2022]

Ertugliflozin, a sodium glucose co-transporter type 2 inhibitor, has shown significant improvements in glycaemic control in type 2 diabetes patients during the VERTIS phase III clinical trial program.

Ertugliflozin, both as a standalone treatment and in combination with other medications like metformin and sitagliptin, has been approved by the US FDA and received positive feedback from the EU for its effectiveness in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ertugliflozin: First Global Approval. Markham, A.[2019]

Steglatro (ertugliflozin) has been shown to effectively improve glycemic control in adults with type-2 diabetes mellitus, making it a valuable option for managing this condition.

The efficacy of Steglatro was evaluated through clinical trials, demonstrating its ability to lower blood sugar levels in patients, which is crucial for preventing complications associated with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ertugliflozin (Steglatro): A New Option for SGLT2 Inhibition. Kovacich, N., Chavez, B.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10212814/

Ertugliflozin and incident obstructive sleep apnea: an analysis ... Conclusions. In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35596030/

Ertugliflozin and incident obstructive sleep apnea - PubMed Conclusions: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to ...

3. uhhospitals.org uhhospitals.org/for-clinicians/articles-and-news/articles/2022/11/collab-between-uhhvi-and-yale-university-studies-pharmacologic-treatment-for-obstructive-sleep-apnea

Collab Between UHHVI and Yale University Studies ... Study participants will wear a biosensing wrist device that gathers data on sleep duration and efficiency, receive 24-hour home blood pressure ...

4. utsouthwestern.elsevierpure.com utsouthwestern.elsevierpure.com/en/publications/ertugliflozin-and-incident-obstructive-sleep-apnea-an-analysis-fr

Ertugliflozin and incident obstructive sleep apnea Conclusions: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature ...

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11682

Evaluating the potential of metabolic drugs in obstructive ... Remarkably, among the patients without OSA at baseline, empagliflozin treatment was associated with a 52% lower incidence of new-onset OSA compared with placebo ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05612594

Study Details | NCT05612594 | Adipose Dysfunction, ... The primary objective of this study is to determine whether bexagliflozin 20 mg once daily compared with placebo reduces the apnea hypopnea index (AHI) in ...

7. jmsnew.ump.edu.pl jmsnew.ump.edu.pl/index.php/JMS/article/download/1226/1169

Bexagliflozin – evaluation of the clinical efficacy, safety ... In 2027, a trial is scheduled to be completed to evalu- ate the impact of bexagliflozin on the severity of sleep apnoea in overweight or obese adults, compared ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37568270/

A Review of the Safety and Efficacy of Bexagliflozin for ... Bexagliflozin appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2D.

9. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05612594/adipose-dysfunction-imaging-physiology-and-outcomes-with-sodium-glucose-cotransporter-2-inhibitor-sglt2i-for-sleep-apnea-the-adiposa-study

The ADIPOSA Study | Clinical Research Trial Listing The primary objective of this study is to determine whether bexagliflozin 20 mg once daily compared with placebo reduces the apnea hypopnea ...

10. researchgate.net researchgate.net/publication/392955778_Bexagliflozin_-_evaluation_of_the_clinical_efficacy_safety_profile_and_potential_new_applications_of_the_SGLT2_inhibitor_a_review_of_the_literature

(PDF) Bexagliflozin - evaluation of the clinical efficacy ... Its efficacy, safety, and potential benefits of new uses are analyzed. Material and methods. Sources were obtained using PubMed and Google ...