Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07472920

Empagliflozin Adjunctive Therapy in Bipolar Depression

Bipolar disorder is a long-term mental health condition that causes mood changes, with depressive episodes being the most frequent and disabling. Many people do not fully recover with current treatments, showing the need for new therapeutic options.

Recent research shows that insulin resistance (IR), a condition in which the body does not respond well to insulin, is common in people with bipolar disorder. It is linked to more severe mood symptoms, poorer treatment response, and higher risk of heart disease. IR may raise inflammation and affect how the brain uses energy, which can influence mood regulation.

Empagliflozin is a medicine approved for type 2 diabetes. In addition to its metabolic and heart benefits, studies suggest that it may also protect the brain and reduce inflammation, possibly helping to improve mood.

This open-label, proof-of-concept clinical trial will test how well empagliflozin works and how safe it is as an add-on treatment for people with bipolar depression and insulin resistance. A total of 20 adults with bipolar disorder type I or II, currently in a depressive episode, will take part in the study over a 12-week period.

The main goal is to see whether empagliflozin can lower depressive symptoms, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Other measures include changes in insulin resistance and incidence of adverse events.

The study aims to explore whether improving insulin resistance can help both mood and metabolic health in people with bipolar disorder, guiding future clinical research.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Bipolar Disorder Bipolar Depression Bipolar and Related Disorders Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Mental Disorders Metabolic Diseases Mood Disorders Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Institute of Psychiatry, University of São Paulo Medical School (IPq-FMUSP)

São Paulo, 05403-903, Brazil

Location contact

Eliana Landivar

CONTACT

[email protected]

+55 11 2661 7890

Eliana Landivar, MD

PRINCIPAL_INVESTIGATOR

About this study

This study is an open-label, single-arm, proof-of-concept clinical trial evaluating empagliflozin as an adjunctive treatment for bipolar depression in individuals with insulin resistance. Adults with bipolar disorder type I or II who are currently experiencing a depressive episode and receiving stable pharmacological treatment will receive empagliflozin for 12 weeks.

Depressive symptom severity will be assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Insulin resistance will be evaluated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and safety will be monitored through assessment of treatment-emergent adverse events throughout the study period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults aged 18 to 65 years.
  • Diagnosis of Bipolar Disorder type I or II according to DSM-5 criteria, confirmed by the MINI International Neuropsychiatric Interview.
  • Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 15 at screening.
  • Currently receiving stable pharmacological treatment for bipolar disorder, with no medication changes (addition or withdrawal) in the past 4 weeks.
  • Ability to provide informed consent.
  • Insulin resistance, defined as HOMA-IR ≥ 1.8.

Exclusion criteria

  • History of hypersensitivity to empagliflozin or any SGLT2 inhibitor.
  • Type 1 or type 2 diabetes mellitus or HbA1c ≥ 6.5% at screening.
  • Known pancreatic disease (pancreatitis or pancreatic surgery).
  • Chronic kidney disease (eGFR < 30 mL/min/1.73m²).
  • Recurrent genital fungal infections.
  • Pregnant or breastfeeding.
  • Alcohol abuse or dependence within the past 12 months.
  • YMRS score ≥ 12 (presence of manic or hypomanic symptoms).

Treatment and study plan

Empagliflozin (EMPA)

Drug

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor administered orally once daily. Participants will start with 10 mg/day for the first 2 weeks, followed by 25 mg/day for the next 10 weeks, completing a 12-week intervention period. The drug will be used as an adjunctive treatment to standard psychiatric therapy in adults with bipolar depression and insulin resistance. Safety and tolerability will be monitored throughout the study.

Other names: Jardiance

Primary outcomes

  1. Change in depressive symptom severity (MADRS total score)

    Time frame: Baseline and 12 weeks after treatment initiation

    The Montgomery-Åsberg Depression Rating Scale (MADRS) will be used to assess depressive symptom severity. The scale includes 10 clinician-rated items, with higher scores indicating more severe depression. The primary outcome is the change in total MADRS score from baseline to week 12 of treatment with empagliflozin.

Secondary outcomes

  1. Change in insulin resistance (HOMA-IR)

    Time frame: Baseline and 12 weeks after treatment initiation

    Insulin resistance will be assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting glucose and insulin levels. The outcome will be the change in HOMA-IR from baseline to week 12.

  2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

    Time frame: Throughout the 12-week study period

    Adverse events will be recorded throughout the 12-week study period. Safety will be assessed through adverse event monitoring, clinical evaluation, and laboratory tests (including renal function and electrolytes).

Study contacts

Contact information is provided by the study sponsor or research team.

Eliana Landivar, MD

CONTACT

[email protected]

+55 11 2661 7890

Sponsors and collaborators

Lead sponsor

University of Sao Paulo

Other

Collaborators

  • Medical school of the University of São Paulo (FMUSP)

Registry information

Official study title

Empagliflozin as an Adjunctive Strategy for Treating Bipolar Depression in Patients With Insulin Resistance: A Proof-of-Concept Study (EMPA-BD)

Acronym: EMPA-BD

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
Mar 16, 2026
Registry last updated
Mar 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.