Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)

NCT ID: NCT05182970

Last Updated: 2024-04-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 5160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2026-05-31

Brief Summary

Prediabetes is associated to an increased risk of cardiovascular disease and mortality. Although metformin can delay progression to diabetes there is a lack of RCTs evaluating the effect of metformin on cardiovascular outcomes. MIMET aims to investigate if addition of metformin to standard care has effects on the occurrence of cardiovascular events after acute myocardial infarction in patients with newly detected prediabetes (identified by oral glucose tolerance test, HbA1c or fasting glucose levels).

Detailed Description

The study is a national multicenter R-RCT associated to the The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART registry) where participants, after informed consent, will be randomly assigned to either open treatment with standard care + metformin or standard care alone in a 1:1 ratio. Standard care consists of diet and life-style advice according to national guidelines but does not include metformin. Baseline data for individual patients will be collected from the SWEDEHEART registry. Patients will be followed per routine care at 2 and 12 months post index AMI and in addition at a final study visit at 24 months. Laboratory measurements and collection of SAE will be performed yearly. In total n=5150 patients is expected to be followed for major CV event (all-cause mortality, myocardial infarction, heart failure and stroke) by linkage with SWEDEHEART and national health registries.

Conditions

PreDiabetes; Acute Myocardial Infarction; Non ST Elevation Myocardial Infarction; ST Elevation Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Metformin on top of standard care

Metformin will be prescribed by the Investigator at the study site and dispensed at pharmacy of choice by the patient. Metformin will be recommended to be gradually titrated to minimize gastrointestinal side effects with a start dose of 500 mg 1x1 for 1 week and thereafter 500 mg 1x2 with an individualised target dose of 2000 mg daily depending on tolerability. The goal is to a have minimal dose of 500 mg 1x2. Patients will be informed to stop medication in events of sever nausea, vomiting or dehydration according to standard practice. The threshold for metformin titration or adding another drug during follow-up is recommended to be assessed individually by the Investigator at the study site, responsible for the patient. Patients with eGFR \<60 cannot be included in the MIMET study. If GFR is between 30-45 ml/min during the study, metformin should be reduced to 1000 mg daily. Metformin is contraindicated if GFR \<30 ml/min. Standard care will be the same as in the control arm.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Individualised target dose of 2000 mg daily depending on tolerability.

Standard care alone

Standard care according to national guidelines. In Sweden there is no pharmacological intervention recommended for individuals with prediabetes at present. Standard care includes diet and life-style advice, which will be given to both groups in the same manner according to local routines, based on the present guidelines. Secondary preventive treatment includes physical activity, participating in exercise program, dietary habits, BMI and or waist circumference, smoking and EQ-5D will be followed in accordance with the routinely reported SWEDEHEART-SEPHIA variables.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Metformin

Individualised target dose of 2000 mg daily depending on tolerability.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

I. AMI

II. Swedish citizens with a personal ID number ≥18 years and ≤80 years

III. Newly diagnosed prediabetes:

1. HbA1c 42-47 mmol/mol or

2. Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or

3. 2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or

4. 2-h post-load venous plasma glucose concentration 7.8-11.0 mmol/L

5. HbA1c <48 mmol/mol and 2-hour post-load capillary glucose concentration >12.1 mmol/L or 2-h post-load venous plasma glucose concentration >11.0 mmol/L (thus elevated 2-hour glucose levels in the diabetes range but without HbA1c levels diagnostic for diabetes)

IV. Naïve to metformin and other glucose lowering therapy

V. Signed informed consent

Exclusion Criteria

I. Type 1 diabetes

II. Known type 2 diabetes

III. Indication for glucose lowering treatment

IV. Acute condition with high risk for volume depletion, circulatory shock, hypoxia

V. Serious illness, other than cardiovascular, with short life expectancy

VI. Renal failure (eGFR <60ml/min)

VII. Hepatic failure

VIII. Malignancy within the last year

IX. Contraindication or hypersensitivity to the study drug

X. Alcohol or drug abuse

XI. Pregnancy or breastfeeding

XII. Women of childbearing potential without adequate anticonception during any part of the study period

XIII. Previous hospitalisation for lactic acidosis

XIV. Predicted inability to comply with the study protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Capio Sankt Görans Hospital

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: collaborator

The Swedish Research Council

OTHER_GOV

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Anna Norhammar

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anna Norhammar, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Medicinkliniken, Ljungby Hospital

Ljungby, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Anna Norhammar, MD, Prof.

Role: CONTACT

anna.norhammar@ki.se

+46858701568

Viveca Ritsinger, MD, PhD

Role: CONTACT

viveca.ritsinger@ki.se

+46372585000

Facility Contacts

Thomas Aronsson, Head of Clinic

Role: primary

References

Ritsinger V, Hagstrom E, Hambraeus K, James S, Jernberg T, Lagerqvist B, Leosdottir M, Lundman P, Pernow J, Ostlund O, Norhammar A. Design and rationale of the myocardial infarction and new treatment with metformin study (MIMET) - Study protocol for a registry-based randomised clinical trial. J Diabetes Complications. 2023 Oct;37(10):108599. doi: 10.1016/j.jdiacomp.2023.108599. Epub 2023 Aug 30.

Reference Type: DERIVED

PMID: 37683518 (View on PubMed)

Other Identifiers

2019-05382

Identifier Type: -

Identifier Source: org_study_id