Effect of Glp-1 and Antidiabetic sgLT2 Agents for myoCardial infarcTion and Ultrasensitive Inflammatory Surveillance (GALACTUS Trial) (GALACTUS)

GLP-1 and Antidiabetic SGLT2 Agents for Myocardial Infarction and Ultrasensitive Inflammatory Surveillance: An Open-Label Pilot Study

The primary risk factor for coronary artery disease is atherosclerosis, with inflammation playing a crucial role in the development and progression of this condition. It has now been proven that inflammation is key in the development of complications after an acute myocardial infarction. These complications can be immediate and mechanical, such as ventricular wall rupture and ventricular arrhythmia, or long-term, presenting as major cardiovascular events like heart failure.

During acute myocardial infarction (AMI), circulating high-sensitivity CRP levels increase approximately 6 hours after the onset of ischemia. CRP levels measured between 24 and 72 hours after symptom onset are a significant prognostic marker for one-year outcomes. Higher high-sensitivity CRP levels at the time of AMI are linked to more severe coronary atherosclerotic lesions seen on angiography and lower LVEF one month after the event. A serum high-sensitivity CRP concentration greater than 10 mg/L after an AMI indicates inflammation, reflecting myocardial necrosis, plaque rupture, and acute thrombosis. In patients with AMI, persistent or increasing CRP levels are strongly associated with a higher risk of all-cause and non-cardiovascular death, especially when inflammation (CRP > 2.0 mg/L) continues for a year.

Aside from reperfusion therapy, very few pharmacological approaches have been used to reduce inflammation after AMI. One such approach was the use of colchicine in the COVERT-MI randomized, double-blind, multicenter trial. This trial compared five days of oral colchicine with a placebo and found no difference in infarct size between the groups at five days or three months, as measured by cardiac magnetic resonance imaging.

SGLT-2 inhibitors are drugs that have revolutionized the management of cardiovascular diseases, offering proven benefits for patients with heart failure and notable nephroprotective effects. However, their use after acute myocardial infarction has not yet been sufficiently established, as the only two published clinical trials so far failed to meet their primary goal of reducing hospitalizations for heart failure. Additionally, evidence of their use in post-AMI inflammation exists only in experimental studies. In experimental studies, SGLT2 global-knockout (KO) mice were used to demonstrate that dapagliflozin significantly influences cardiac fibrosis and inflammation, and markedly alters the gene expression profiles of macrophages and fibroblasts. Moreover, dapagliflozin directly inhibited macrophage-mediated inflammation, thereby suppressing cardiac fibroblast activation.

Similarly, only experimental studies have shown that semaglutide decreases elevated levels of TNF-α, IL-6, ROS, and MDA in the serum and cardiac tissues of obese mice. By lowering the expression of Cxcl2, S100a8, and S100a9 in neutrophils, semaglutide may help reduce cardiac inflammation and oxidative stress.

Therefore, the objective of this study is to compare the effects of dapagliflozin and semaglutide on inflammatory markers (hs-CRP and IL-6) in patients with acute ST-segment elevation myocardial infarction.

Study Overview

• Status: Recruiting
• Conditions: Acute Myocardial Infarction With ST Elevation
• Intervention / Treatment: Drug: Dapagliflozin 10 MG Oral Tablet; Drug: Semaglutide (Rybelsus®)

Detailed Description

This is a small open-label pilot clinical trial to assess the effectiveness of dapagliflozin and semaglutide on inflammatory markers (IL-6 and hs-CRP) in patients with STEMI over 24 weeks. It will include patients over 18 years old with STEMI, with or without a diagnosis of type 2 diabetes, clinical obesity, and an initial serum hs-CRP level greater than 2.0 mg/L.

Inflammation markers will be measured upon patient admission after percutaneous coronary intervention and again after 24 weeks of treatment with the drugs. Patients will be discharged in accordance with STEMI treatment guidelines, and their medication adherence and tolerability will be monitored.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hilda Elizabeth Macías-Cervantes, Ph.D.; Phone Number: 31315 +52 477 7171 4800; Email: hildamacer@gmail.com

Study Locations

• Mexico
  • Guanajuato
    • León, Guanajuato, Mexico, 37320
      • Recruiting
      • Hospital de Especialidades No.1, Centro Médico Nacional del Bajío
      • Contact: Rodolfo Guardado-Mendoza, Ph.D.; Phone Number: 3683 +52 477-2674900; Email: guardamen@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Criteria for the fourth definition of acute myocardial infarction with ST-segment elevation.
• Diagnosed with type 2 diabetes.
• Initial serum high-sensitivity CRP value > 2.0 mg/L.
• Clinically obese.
• LVEF >50%.

Exclusion Criteria:

• Patients who have recently received immunosuppressive therapy
• Patients with a history of ischemic heart disease
• Known allergy to any of the medications used
• Use of any of the study drugs more than 6 months prior to randomization
• Patients experiencing diabetic ketoacidosis
• Patients with hemodynamic instability (mean arterial pressure <60 mmHg while on vasopressors)
• Pregnant women
• Patients with a history or current diagnosis of cancer
• Patients with documented active infections, such as pneumonia or urinary tract infections
• Patients with pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Semaglutide; Semaglutide 3 mg, gradually increasing to 14 mg every 24 hours over 24 weeks.	Drug: Semaglutide (Rybelsus®); Semaglutide 3 mg, gradually increasing to 14 mg every 24 hours over 24 weeks.
Experimental: Dapagliflozin; Dapagliflozin 10 mg daily for 24 weeks	Drug: Dapagliflozin 10 MG Oral Tablet; 10 mg dapagliflozin daily for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers (high-sensitivity PCR)	Patients with hsCRP > 2 mg/L will be included, and a control will be taken to assess the change after 24 weeks of treatment.	24 weeks.
Inflammatory markers (interleukin 6)	Patients with IL-6 > 2 ng/L will be included, and a control will be taken to assess the change after 24 weeks of treatment.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epicardial fat	Epicardial fat will be assessed using non-invasive coronary tomography during hospitalization for STEMI and again after 24 weeks of treatment.	24 weeks
LDL cholesterol	The impact of both interventions on LDL levels will be assessed after 24 weeks of treatment.	24 weeks
Change in glucose and HbA1c	The effect of both interventions on fasting glucose and HbA1c levels will be assessed after 24 weeks of treatment.	24 weeks

Collaborators and Investigators

• Sponsor: Instituto Mexicano del Seguro Social
• Collaborators: Universidad de Guanajuato
• Investigators: Principal Investigator: Rodolfo Guardado-Mendoza, Ph.D., Universidad de Guanajuato

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Estimated): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Dapagliflozin; Semaglutide; STEMI; High-sensitivity PCR
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; ST Elevation Myocardial Infarction; semaglutide; dapagliflozin
• Other Study ID Numbers: F-2024-1001-136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No