What side effects are associated with this type of intervention?

SGLT2 inhibitors, such as empagliflozin, primarily used for diabetes management, have been studied for their potential benefits in depression due to their ability to increase ketone bodies, which may serve as an alternative energy source for the brain. Common side effects of SGLT2 inhibitors include urinary tract infections, genital mycotic infections, and a potential risk of diabetic ketoacidosis. For broader depression treatments, common side effects of antidepressants like SSRIs and SNRIs include nausea, weight gain, sexual dysfunction, insomnia, and dry mouth.

What prior FDA approvals exist?

The FDA has approved several classes of medications for the treatment of depression, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine, and atypical antidepressants like bupropion. While SGLT2 inhibitors like empagliflozin are being studied for their potential benefits in depression due to their ability to increase ketone bodies as an alternative energy source for the brain, they are not yet approved for this indication. Current FDA-approved treatments focus on modulating neurotransmitter levels to alleviate depressive symptoms.

What other types of research exist?

Promising alternatives to Empagliflozin for depression treatment in 2024 include: 1) Ketogenic diets, which naturally increase ketone body production and have shown potential benefits for mood disorders. 2) Exogenous ketone supplements, which directly provide ketone bodies as an energy source. 3) GLP-1 receptor agonists like liraglutide and semaglutide, which have shown potential benefits for mood and cognitive function. 4) Novel antidepressants targeting different pathways, such as NMDA receptor antagonists (e.g., esketamine) and neurosteroid modulators (e.g., brexanolone).

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SGLT2 Inhibitor

SGLT2 Inhibitor for Depression

Phase 2

Recruiting

Led By Dan V Iosifescu, MD, MMSc

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Current/acute Major Depressive Disorder (MDD) diagnosis, per MINI psychiatric interview;

Provide written informed consent, as approved by the NYU Institutional Research Ethic Board (IRB)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 6

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Empagliflozin may cause urinary tract infections, dehydration leading to low blood pressure, genital yeast infections in women and men, increased cholesterol levels and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with Major Depressive Disorder recently.

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

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I am between 18 and 65 years old.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 6

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 6

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 6 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score

Secondary study objectives

Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score

Change from Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Score

Side effects data

From 2021 Phase 3 trial • 5988 Patients • NCT03057951

15%

Cardiac failure

Hypertension

Hypotension

Urinary tract infection

Renal impairment

Hyperkalaemia

Fall

Atrial fibrillation

Diabetes mellitus

Hyperuricaemia

Anaemia

Acute kidney injury

Pneumonia

COVID-19

Death

Acute myocardial infarction

Cardiac failure congestive

Basal cell carcinoma

Cardiac failure chronic

Cellulitis

Syncope

Chronic kidney disease

COVID-19 pneumonia

Ischaemic stroke

Coronary artery disease

Chronic obstructive pulmonary disease

Myocardial infarction

Sepsis

Transient ischaemic attack

Angina unstable

Cerebrovascular accident

Angina pectoris

Ventricular tachycardia

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

10 mg Empagliflozin

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Participants with Major Depressive Disorder (MDD)Experimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Empagliflozin

2017

Completed Phase 4

~181750

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for depression include selective serotonin reuptake inhibitors (SSRIs), which increase serotonin levels in the brain, and serotonin-norepinephrine reuptake inhibitors (SNRIs), which boost both serotonin and norepinephrine. These neurotransmitters are crucial for mood regulation. Another class, tricyclic antidepressants (TCAs), also increase neurotransmitter levels but with more side effects. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of neurotransmitters, increasing their availability. These mechanisms are vital as they help correct the chemical imbalances thought to underlie depression. Recently, SGLT2 inhibitors like empagliflozin are being studied for their potential to reduce depressive symptoms by increasing ketone bodies, providing an alternative energy source for the brain, which may be beneficial in energy metabolism disturbances seen in depression.

Fluoxetine induces glucose uptake and modifies glucose transporter palmitoylation in human peripheral blood mononuclear cells.Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders?Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation.