Dapagliflozin as Prophylaxis for Glucocorticoid-Induced Hyperglycemia

Phase 2

Active, not recruiting

• Conditions: Dapagliflozin (Forxiga); Hyperglycaemia; Glucocorticoid
• Interventions: Drug: Dapagliflozin (DAPA)

• Registration Number: NCT06748105
• Lead Sponsor: Lauro Fabián Amador Medina

Brief Summary

The goal of this clinical trial is to investigate whether dapagliflozin can help prevent glucocorticoid-induced hyperglycemia (GIH) in hospitalized patients requiring high-dose glucocorticoids (GCs). This trial will also assess the safety of dapagliflozin when used alongside GCs. The main questions the trial aims to answer are:

Does dapagliflozin reduce the incidence of GIH in patients receiving high-dose GCs? What side effects or adverse events occur in patients taking dapagliflozin alongside high-dose GCs? Researchers will compare dapagliflozin to standard glucose monitoring (SGM) to determine if dapagliflozin is effective in preventing GIH in patients receiving high doses of GCs.

Participants will:

Take dapagliflozin (10 mg/day) or undergo standard glucose monitoring during their hospital stay.

Visit the hospital for regular check-ups and glucose testing during their treatment.

Record their glucose levels multiple times a day and report any adverse events they experience.

Detailed Description

This clinical trial aims to evaluate the efficacy and safety of dapagliflozin in preventing glucocorticoid-induced hyperglycemia (GIH) in hospitalized patients who require high-dose glucocorticoid (GC) treatment. GCs are commonly used in clinical practice for their potent anti-inflammatory and immunosuppressive properties, but they are also a major cause of medication-induced hyperglycemia, particularly when administered at high doses.

The hypothesis of this trial is that dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, may reduce the incidence of GIH by counteracting the metabolic disturbances caused by GCs. Dapagliflozin works by inhibiting the SGLT2 protein, which is responsible for glucose reabsorption in the kidneys. By inhibiting this protein, dapagliflozin promotes glucose excretion in the urine, helping to reduce blood glucose levels. This mechanism is particularly relevant in the context of GIH, as GCs can impair insulin secretion, promote hepatic gluconeogenesis, and increase peripheral insulin resistance.

The primary aim of the study is to compare the incidence of GIH in patients receiving dapagliflozin versus those undergoing standard glucose monitoring (SGM) while on high-dose GCs. Secondary objectives include assessing the cumulative incidence of GIH days, the number of hyperglycemic crises, and the need for insulin therapy. The study also evaluates the safety profile of dapagliflozin, particularly focusing on any adverse events associated with its use in this population. The adverse effects of high-dose GCs will also be reported to provide a broader context for understanding the potential risks of treatment.

This randomized, open-label, controlled clinical trial will enroll hospitalized patients aged 18 and older who require high-dose GC therapy (prednisone equivalents \>30 mg/day). The study will be conducted at the High Specialty Medical Unit, Hospital of Specialties No. 1, National Medical Center of Bajío, Mexican Institute of Social Security. Participants will be randomly assigned to one of two groups: the dapagliflozin group (10 mg/day) or the control group receiving standard glucose monitoring (SGM).

Both groups will undergo routine glucose monitoring through capillary glucose checks (three times daily) and fasting central glucose assessments. The study will be conducted during the patients' hospitalization, and participants will be followed until discharge or up to 10 days, whichever occurs first. The dosing schedule for dapagliflozin will ensure it is administered synchronously with the GC dose (within 12 hours of GC administration).

Additionally, data regarding the incidence of insulin therapy use, as well as the incidence and duration of hyperglycemic crises (defined as ≥2 persistent glucose readings ≥180 mg/dL within 24 hours), will be carefully recorded and analyzed. Adverse events will be monitored throughout the study, with particular attention to renal function, as SGLT2 inhibitors have been associated with potential renal side effects in some patient populations.

The statistical analysis will be based on comparing the two treatment arms for the incidence of GIH using appropriate methods, including Chi-square tests for categorical variables and Kaplan-Meier survival analysis for cumulative hyperglycemia-free days. All analyses will be conducted with a significance level set at p \< 0.05, and SPSS v20 will be used for statistical processing.

The findings from this study could provide critical insights into the potential role of dapagliflozin in preventing GIH in high-risk hospitalized patients, improving patient outcomes, and offering a new therapeutic strategy in managing hyperglycemia associated with glucocorticoid therapy.

Study Timeline

• Status Verified: 2024-12
• Study Start: 2024-12-01
• Study First Submitted: 2024-12-17
• Study First Submitted QC: 2024-12-20
• Last Update Submitted: 2024-12-20
• Study First Posted: 2024-12-27
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Patients over 18 years old admitted to the emergency department with a need for hospitalization, under the care of the Internal Medicine and Hemato-Oncology departments, from May to November 2024.
• Patients with a clinical indication for high-dose glucocorticoid use (prednisone bioequivalence >30mg/day).

Exclusion Criteria

• Current treatment with SGLT2 inhibitors, sulfonylureas, or insulin infusion pumps.
• Contraindications for SGLT2 inhibitors: chronic kidney disease (KDIGO stage IV), acute kidney injury or disease, type 1 diabetes, suspected severe acute infection, requirement for surgery, severe urinary tract infection.
• Previous use of high-dose glucocorticoids within the last 30 days. Indication for aggressive fluid resuscitation, use of vasopressors, use of mineralocorticoids, requirement for invasive mechanical ventilation, or classified as critically ill.
• Uncontrolled hyperglycemia (>140mg/dL despite proper treatment) or suspected euglycemic diabetic ketoacidosis.
• Use of glucocorticoids in the past 28 days with doses higher than medium doses (prednisone equivalence >10mg and <30mg/day).
• Inability to take dapagliflozin orally.
• Pregnancy, postpartum, or lactation.
• Patients with incomplete follow-up or inadequate adherence to the intervention protocol, or those who experience adverse effects related to dapagliflozin use.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Monitoring Arm	Dapagliflozin (DAPA)	Participants will undergo standard glycemic monitoring (SGM), including preprandial capillary glucose measurements during three daily shifts and fasting central glucose assessments (6-8 hours fasting).
Dapagliflozin	Dapagliflozin (DAPA)	Participants in this arm will receive dapagliflozin (10 mg/day) administered orally. The dose will be synchronized with glucocorticoid administration, with a maximum allowable time difference of 12 hours. Patients and their families will be trained in self-administration, and adherence will be monitored through nursing service reports.

Primary Outcome Measures

Name	Time	Method
hyperglycemia crisis	until hospital discharge, an avarage of 10 days	Hyperglycemic Crisis (HC): Defined as the persistence of ≥2 events of capillary or central glucose ≥180mg/dL (\>10 mmol/L) within 24 hours.
Incidence of glucocorticoid-induced hyperglycemia	until hospital discharge, an average of 10 days	HIG (Severe Intermittent Hyperglycemia): Defined as the persistence of ≥2 events of capillary or central glucose ≥140mg/dL (7.8 mmol/L) within 24 hours.

Secondary Outcome Measures

Name	Time	Method
incidence of insulin therapy.	until hospital discharge, an average of 10 days	To determine the incidence (%) of insulin therapy use in both study arms.
Report adverse events.	until hospital dischargte, an average of 10 days	Report adverse events associated (%) with dapagliflozin use in the study population

Trial Locations

Locations (1)

Unidad Medica de Alta Especialidad Hospital de Especialidades No. 1 CMN Bajio; 🇲🇽 Leon, Guanajuato, Mexico