Effect of Empagliflozin on Metabolic Outcomes in Adults Living With HIV Receiving Dolutegravir-Based Therapy

January 2, 2026 updated by: Abdelrahman Mahmoud

Role of Empagliflozin in Metabolic Changes Associated With Antiretroviral Therapy in Human Immunodeficiency Virus

We investigate the role of empagliflozin in the treatment of obesity in PLWH.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

HIV remains a major global public health concern. In 2024, approximately 40.8 million people were living with HIV worldwide. Around 630,000 deaths occurred due to AIDS-related illnesses. The preferred first-line ART regimen includes: Tenofovir disoproxil fumarate (TDF)+Emtricitabine (FTC) or Lamivudine (3TC)+Dolutegravir (DTG).

The introduction of highly active antiretroviral therapy transformed HIV from a fatal disease into a manageable chronic condition, significantly reducing morbidity and mortality.

Integrase strand transfer inhibitors (INSTIs), particularly dolutegravir (DTG), have been associated with greater weight gain compared with non-INSTI antiretroviral regimens.

The observed weight gain is strongly linked to adverse metabolic outcomes, including increased incidence of metabolic syndrome, higher rates of insulin resistance, and dyslipidemia.

Individuals living with HIV receiving antiretroviral therapy (ART) have been shown to have approximately 1.5-fold higher odds of developing metabolic syndrome (MetS).

Over the long term, these alterations contribute to a significantly elevated risk of cardiovascular disease, including myocardial infarction and stroke.

Evidence from biopsy-based studies further demonstrates a substantial burden of (NAFLD), (NASH), and liver fibrosis among people living with HIV (PLWH).

On the other hand, Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated:

Cardiovascular benefits: Reduction in major adverse cardiovascular events in patients with atherosclerotic disease, including those with hypertension, dyslipidemia, and obesity.

Metabolic control: Improved glycemia via renal glucose reabsorption inhibition, lowering hyperglycemia with minimal hypoglycemic risk.

Weight and metabolic effects: Reduced body weight, BMI, SBP, visceral adiposity, insulin resistance, improved oral glucose tolerance test (OGTT) values and fasting insulin, even in non-diabetic individuals.

Hepatic outcomes: Significant reduction in liver fat content in metabolic disorders, mediated by improved lipid metabolism, insulin sensitivity, and reduced hepatic inflammation, supporting metabolic dysfunction-associated steatotic liver disease (MASLD) management.

These combined effects make SGLT2 inhibitors a promising therapeutic option for addressing the multiple facets of metabolic syndrome.

Study Type

Interventional

Enrollment (Estimated)

66

Phase

  • Phase 2

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 Contact Backup

Study Locations

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:

  • Age >18 years up to 65 years old.
  • Body Mass Index (BMI) > 30 kg/m^2.
  • Currently receiving an integrase strand transfer inhibitor (INSTI)-based regimen (dolutegravir-based ART).
  • Sustained virologic suppression, defined as HIV-1 RNA < 200 copies/mL for at least 6 months.
  • Current CD4 count > 250 cells/mL.
  • Ability and willingness to provide written informed consent.

Exclusion Criteria:

  • Diagnosis of Diabetes Mellitus, defined as a fasting blood glucose level > 126 mg/dL or glycated hemoglobin (HbA1c) > 6.5% (or per ADA definition).
  • Renal impairment (e.g., eGFR < 60 ml/min/1.73m^2).
  • Active viral hepatitis B or C.
  • Hypersensitivity to empagliflozin or any of its excipients.
  • Pregnancy or breastfeeding.
  • Current use of other SGLT-2 inhibitors.
  • Drugs that may interact with empagliflozin (e.g., rifampin or phenytoin) or dolutegravir (e.g., antacids, carbamazepine, or phenytoin).
  • Current or recent use of medications known to be associated with significant weight gain (e.g., systemic corticosteroids, antipsychotics, mood stabilizers, or other agents with established weight-promoting effects).
  • Known thyroid disease, defined as TSH > 6.0 mIU/L or < 0.35 mIU/L

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control Group
Patients in the control group will receive an identical placebo and Standard Antiretroviral Therapy (ART)
Drug: Placebo
TDF/FTC+DLG
Other Names:
  • Group A
  • Inactive Substance
Experimental: EMPA Group + SOC
Patients in the intervention arm will receive Empagliflozin 10 mg once daily for 6 months in addition to the standard DTG-based antiretroviral therapy.
Drug: Empagliflozin (oral)

Empagliflozin is an oral medication used primarily to treat type 2 diabetes. It belongs to a class of drugs called SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors). Empagliflozin blocks SGLT2 proteins in the kidneys.

This prevents glucose reabsorption, causing excess sugar to be excreted in urine.

It helps lower blood sugar levels and can also reduce body weight and blood pressure.

Other Names:
  • Mellitofix 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight change
Time Frame: 6 months
Weight will be measured in kilograms using a calibrated scale from baseline to 6 months in PLWH on dolutegravir-based antiretroviral therapy.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Total Cholesterol
Time Frame: 6 months
Effects of empagliflozin versus placebo on Concentration of total cholesterol in serum, measured in mg/dL.
6 months
Change in Fasting Blood Glucose
Time Frame: 6 months
Concentration of glucose in blood plasma, measured in mg/dL after a minimum 8-hour overnight fast.
6 months
Change in Glycated Hemoglobin (HbA1c)
Time Frame: 6 months
The percentage of glycated hemoglobin in the blood, used as an indicator of long-term glycemic control.
6 months
Change in Serum Creatinine
Time Frame: 6 months
Concentration of creatinine in the blood, measured in mg/dL
6 months
Change in Systolic and Diastolic Blood Pressure
Time Frame: 6 months
Measured in millimeters of mercury (mmHg) while the participant is in a seated position. at baseline, 3 and 6 months.
6 months
Change in Body Mass Index (BMI)
Time Frame: Baseline and 6 months
BMI is a calculation of body weight relative to height. It will be calculated as weight in kilograms divided by the square of height in meters (kg/m^2).
Baseline and 6 months
Change in Waist Circumference
Time Frame: Baseline, 3 and 6 months
Waist circumference will be measured using a non-stretchable flexible tape measure. The measurement will be taken at the midpoint between the lowest rib and the iliac crest (top of the hip bone) while the participant is standing and at the end of a normal expiration. Measurements will be recorded in centimeters.
Baseline, 3 and 6 months
Change in Absolute CD4+ T-cell Count
Time Frame: baseline and 6 months
The absolute number of CD4+ T-lymphocytes will be measured in peripheral blood using flow cytometry. Results will be reported in cells per cubic millimeter (cells/mm³).
baseline and 6 months
Change in Plasma HIV-1 RNA Viral Load
Time Frame: baseline and 6 months
Viral load will be quantified using a Real-Time Polymerase Chain Reaction (RT-PCR) assay. Results will be reported in copies per milliliter (copies/mL).
baseline and 6 months

Collaborators and Investigators

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

Sponsor

Abdelrahman Mahmoud

Investigators

  • Study Director: Maggie Abbassi, Prof., Cairo University
  • Principal Investigator: Abedalrahman Dosoky, Cairo University
  • Study Director: Ahmed Kamel, Cairo University

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 (Actual)

September 1, 2025

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

January 2, 2026

First Posted (Actual)

January 13, 2026

Study Record Updates

Last Update Posted (Actual)

January 13, 2026

Last Update Submitted That Met QC Criteria

January 2, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL(3828)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

6 months

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

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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