Empagliflozin Adjunctive Therapy in Bipolar Depression (EMPA-BD)

March 11, 2026 updated by: Beny Lafer, University of Sao Paulo

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • São Paulo
      • São Paulo, São Paulo, Brazil, 05403-903
        • Institute of Psychiatry, University of São Paulo Medical School (IPq-FMUSP)
        • Contact:
        • Principal Investigator:
          • Eliana Landivar, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Empagliflozin Adjunctive Therapy in Bipolar Depression
Participants will receive empagliflozin orally once daily as an adjunct to their usual psychiatric treatment. The dose will start at 10 mg/day for the first 2 weeks and increase to 25 mg/day for the following 10 weeks, totaling a 12-week intervention period. The study will evaluate changes in depressive symptoms, insulin resistance, and metabolic parameters in adults with bipolar depression and insulin resistance. All participants will continue their standard psychiatric medications under medical supervision throughout the study.
Drug: Empagliflozin (EMPA)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 12 weeks after treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 12 weeks after treatment initiation
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).
Throughout the 12-week study period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Medical school of the University of São Paulo (FMUSP)

Investigators

  • Principal Investigator: Beny Lafer, MD, PhD, Institute of Psychiatry, University of São Paulo Medical School (IPq-FMUSP)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 9, 2026

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 5, 2026

First Submitted That Met QC Criteria

March 11, 2026

First Posted (Actual)

March 16, 2026

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 86886125

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The individual participant data (IPD) will not be shared because this is a small, proof-of-concept, single-site study. The dataset includes sensitive clinical information that could potentially identify participants. Only aggregated and anonymized results will be shared in future scientific publications or presentations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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