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

Phase 3RecruitingNCT05182970

Karolinska Institutet5,160 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

5,160

Conditions

PreDiabetes

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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).