Empagliflozin Adjunctive Therapy in Bipolar Depression

NCT07472920 | Not Yet Recruiting

• 1 other identifier: 86886125
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder; Bipolar Depression; Insulin Resistance

Keywords

Bipolar Disorder; Bipolar Depression; Insulin Resistance; Empagliflozin; SGLT2 Inhibitors; Metabolic Psychiatry

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptom severity (MADRS total score)

  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 Outcomes (2)

• Change in insulin resistance (HOMA-IR)

  Baseline and 12 weeks after treatment initiation

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

  Throughout the 12-week study period

Study Arms (1)

Empagliflozin Adjunctive Therapy in Bipolar Depression

EXPERIMENTAL

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)

Interventions

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.

Also known as: Jardiance

Empagliflozin Adjunctive Therapy in Bipolar Depression

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Sao Paulo: lead
• Medical school of the University of São Paulo (FMUSP): collaborator

Study Sites (1)

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

São Paulo, São Paulo, 05403-903, Brazil

Location

MeSH Terms

Conditions

Bipolar Disorder; Insulin Resistance

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Beny Lafer, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eliana Landivar, MD

CONTACT

+55 11 2661 7890; eliana.landivar@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study; no masking will be used.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Model Details: Open-label, single-arm, proof-of-concept trial evaluating the effects of empagliflozin as an adjunctive treatment for bipolar depression.

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 16, 2026
• Study Start: March 9, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)