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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether empagliflozin, a medication typically used for diabetes, can reduce symptoms of depression. The focus is on individuals with Major Depressive Disorder (MDD) to determine if empagliflozin, which alters energy sources in the brain, improves mood. Participants will take the medication daily for six weeks. Those experiencing moderate to severe depression who have not tried more than two unsuccessful antidepressant treatments might be suitable for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research has shown that empagliflozin, a type of medication, is generally well-tolerated. In one study, patients taking empagliflozin for depression felt much better compared to those who took a placebo, a pill with no active medicine. This suggests the treatment might not only be effective but also easy for patients to handle.

Furthermore, a survey found that about one-third of people taking empagliflozin reported feeling better, and only a few mentioned any negative effects. Since empagliflozin is already approved for treating diabetes, this provides additional evidence of its general safety.

Overall, past studies and its approval for other uses indicate that empagliflozin is safe and well-tolerated, with few side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Most treatments for depression, like SSRIs and SNRIs, work by altering neurotransmitter levels in the brain. But empagliflozin works differently, targeting the way the body handles glucose. Originally used for diabetes by inhibiting the SGLT2 protein responsible for glucose reabsorption in the kidneys, empagliflozin may also influence mood by affecting brain energy metabolism and inflammation. Researchers are excited because this novel mechanism could offer relief for patients who haven't responded to traditional antidepressants.

What evidence suggests that empagliflozin might be an effective treatment for depression?

Research has shown that empagliflozin, a drug typically used to lower blood sugar, might help reduce depression symptoms. One study found that people taking empagliflozin experienced a noticeable improvement in their depression compared to those taking a placebo, which contains no active medicine. Another study discovered that combining empagliflozin with citalopram, a common antidepressant, further reduced depression symptoms. The drug may help by providing the brain with a different energy source, potentially improving mood. These findings suggest that empagliflozin could be a promising option for treating depression. Participants in this trial will receive empagliflozin to evaluate its effectiveness in reducing symptoms of major depressive disorder. ^{1 2 6 7 8}

Who Is on the Research Team?

Dan Iosifescu, MD, MSc

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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 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 (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/PMC10895773/

a randomized double-blind, placebo-controlled clinical trial This treatment showed significant improvement in depressive symptoms as compared to placebo. In this clinical trial, a group of 20 patients with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38408937/

a randomized double-blind, placebo-controlled clinical trial We studied the effectiveness of empagliflozin, a blood sugar-lowering drug, as an adjunctive therapy to reduce the severity of depression symptoms.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05757791

NCT05757791 | Sodium-Glucose Cotransporter-2 Inhibitor ... The primary purpose of this study is to determine whether empagliflozin, a medication in a class known as sodium-glucose cotransporter-2 inhibitors (SGLT2) ...

4. 2minutemedicine.com 2minutemedicine.com/empagliflozin-shows-promise-as-an-adjunct-to-selective-serotonin-reuptake-inhibitors-in-reducing-symptom-severity-in-major-depressive-disorder/

Empagliflozin Shows Promise As An Adjunct To Selective ... Combination therapy of empagliflozin and citalopram reduced symptom severity in patients with major depressive disorder.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299925002791

The potential neuroprotective effect of empagliflozin ... In addition, EMPA treatment decreased blood glucose levels by 39 %, decreased serum insulin levels by 60.6 %, decreased HOMA-IR by 76.5 % and ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601683/

Clinical Review - Empagliflozin (Jardiance) - NCBI - NIH According to the HeartLife Foundation survey (N = 12), approximately 33.3% of respondents felt better after taking empagliflozin, while 8.3% reported they felt ...

7. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/2114/pilot-phase-ii-open-label/

A Pilot Phase II Open-Label Single-Center Study of Sodium ... This is an open-label, single arm clinical trial preliminarily testing the antidepressant effects of empagliflozin in patients with major depressive disorder ( ...

8. mdpi.com mdpi.com/2077-0383/13/4/1172

Efficacy and Safety of Antidiabetic Agents for Major ... This meta-analysis aimed to determine the efficacy and safety of antidiabetic agents in the treatment of major depressive disorder and bipolar depression.