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

NCT05182970 | Recruiting Phase 3

• 1 other identifier: 2019-05382
• Study Type: interventional
• Target: 5,160
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Time to major CV event

  Major CV event; a composite endpoint of first of all-cause death or main diagnosis of MI, heart failure or stroke (reported in SWEDEHEART, the National Patient Register and the Cause of Death Register).

  Estimated follow-up for each patient is 1-4 years

Secondary Outcomes (10)

• Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.

  Estimated follow-up for each patient is 1-4 years

• Time to the composite endpoint of all-cause death, main diagnosis of MI, stroke and revascularisation (CABG or PCI >4 months after the index AMI).

  Estimated follow-up for each patient is 1-4 years

• All-cause death

  Estimated follow-up for each patient is 1-4 years

• CV death

  Estimated follow-up for each patient is 1-4 years

• Hospitalisation with MI

  Estimated follow-up for each patient is 1-4 years

Other Outcomes (3)

• Serious Adverse Events

  Estimated follow-up for each patient is 1-4 years

• Lactic acidosis (E11.1D)

  Estimated follow-up for each patient is 1-4 years

• Hypoglycaemia

  Estimated follow-up for each patient is 1-4 years

Study Arms (2)

Metformin on top of standard care

ACTIVE COMPARATOR

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.

Drug: Metformin

Standard care alone

NO INTERVENTION

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.

Interventions

Metformin DRUG

Individualised target dose of 2000 mg daily depending on tolerability.

Metformin on top of standard care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I. AMI
• II. Swedish citizens with a personal ID number ≥18 years and ≤80 years
• III. Newly diagnosed prediabetes:
• HbA1c 42-47 mmol/mol or
• Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or
• hour post-load capillary glucose concentration 8.9-12.1 mmol/L or
• h post-load venous plasma glucose concentration 7.8-11.0 mmol/L
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Capio Sankt Görans Hospital: collaborator
• Uppsala University: collaborator
• The Swedish Research Council: collaborator

Study Sites (1)

Medicinkliniken, Ljungby Hospital

Ljungby, 341 35, Sweden

RECRUITING

Related Publications (1)

• 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.

  PMID: 37683518 DERIVED

MeSH Terms

Conditions

Prediabetic State; Non-ST Elevated Myocardial Infarction; ST Elevation Myocardial Infarction

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Anna Norhammar, MD, Prof.

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Norhammar, MD, Prof.

CONTACT

+46858701568; anna.norhammar@ki.se

Viveca Ritsinger, MD, PhD

CONTACT

+46372585000; viveca.ritsinger@ki.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 10, 2022
• Study Start: December 2, 2021
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)