SGLT2 Inhibitor for Depression

Overseen By David T Liebers, MD, MPhil, MPP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Psychotropics, SGLT2 inhibitors

Disqualifiers: Bipolar, Schizophrenia, Substance use, 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: 6 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether empagliflozin, a medication that helps produce ketone bodies, can reduce depression symptoms. It targets people with depression by providing an alternative energy source for the brain, potentially improving their mood.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain antidepressants like SSRIs, NDRIs, SNRIs, or mirtazapine. However, if you are on other psychotropic medications, you may need to stop them to participate.

Is empagliflozin (Jardiance) safe for humans?

Empagliflozin (Jardiance) is generally safe for humans, but it can cause some side effects like genital infections, especially in women, and a slight increase in mild urinary tract infections. It may also lead to low blood pressure and fluid loss, so monitoring is important, especially for those at risk. ^{1 2 3 4 5}

How does the drug Empagliflozin differ from other treatments for depression?

Empagliflozin is unique because it is primarily used to treat type 2 diabetes by preventing glucose reabsorption in the kidneys, which is different from typical depression treatments that usually target brain chemicals. This novel approach could offer a new pathway for managing depression, especially for those who also have diabetes. ^{2 3 4 6 7}

What data supports the effectiveness of the drug empagliflozin (Jardiance) for treating depression?

Empagliflozin (Jardiance) is primarily used to treat type 2 diabetes by lowering blood sugar levels and has shown benefits like weight loss and reduced blood pressure. It also demonstrated cardiovascular protection in patients with diabetes, which might indirectly suggest potential benefits for mood and mental health, although direct evidence for treating depression is not provided. ^{2 3 4 6 8}

Research Team

Dan Iosifescu, MD, MSc

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for adults aged 18-65 with a current diagnosis of Major Depressive Disorder (MDD), who can provide written consent. It's not suitable for those with personality disorders, liver or kidney disease, hypersensitivity to empagliflozin, history of diabetic ketoacidosis, multiple anti-depressant treatment failures, neurologic/seizure disorders, or psychotic conditions.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder recently.

I have signed the consent form approved by the NYU IRB.

I have been diagnosed with Major Depressive Disorder recently.

Exclusion Criteria

You are allergic to empagliflozin or any of the ingredients in JARDIANCE.

I have had diabetic ketoacidosis in the past.

I've had two or more unsuccessful treatments for my current depression episode.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin 10mg daily for two weeks and then 25mg for four weeks, for a total treatment duration of 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin

Trial Overview The study tests if empagliflozin (an SGLT2 inhibitor) reduces depression symptoms by making ketone bodies as alternative brain fuel. Participants will receive this medication and their mood changes will be observed.

Participant Groups

Group I: Participants with Major Depressive Disorder (MDD) Experimental Treatment 1 Intervention

Patients will receive empagliflozin 10mg daily for two weeks and then empagliflozin 25mg for four weeks, for a total treatment duration of 6 weeks. Patients will be instructed to take the medication each morning, daily, with or without food. The number of doses given may be increased to a small degree to allow for flexibility in the scheduling of follow-up visits.

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?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

American Society of Clinical Psychopharmacology

Collaborator

Trials

1

Recruited

20+

Findings from Research

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]

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 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 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 (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 (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, 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 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]

References

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

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

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

SGLT2 inhibitors: new reports. [2019]

3. Belgium pubmed.ncbi.nlm.nih.gov

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

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

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Diabetes Drug Now Approved for Heart Failure. [2023]

7. England pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

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