Clinical trial NCT05182970: Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)
Official title: The Myocardial Infarction and New Treatment With Metformin Study (MIMET) - a R-RCT to Study Metformin and the Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Newly Detected Prediabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: PreDiabetes
Acute Myocardial Infarction
Non ST Elevation Myocardial Infarction
ST Elevation Myocardial Infarction
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Capio Sankt Görans Hospital
name: Uppsala University
name: The Swedish Research Council
First posted: 2022-01-10
Enrollment: 5160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Time to major CV event
timeFrame: Estimated follow-up for each patient is 1-4 years
Secondary outcomes:
measure: Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke.
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: 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).
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: All-cause death
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: CV death
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Hospitalisation with MI
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Hospitalisation with stroke
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Hospitalisation with heart failure
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: New cancer diagnosis
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Initiation of any glucose lowering therapy
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Diabetes diagnosis
timeFrame: Estimated follow-up for each patient is 1-4 years
Other outcomes:
measure: Serious Adverse Events
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Lactic acidosis (E11.1D)
timeFrame: Estimated follow-up for each patient is 1-4 years
measure: Hypoglycaemia
timeFrame: Estimated follow-up for each patient is 1-4 years
Locations:
city: Ljungby
country: Sweden
facility: Medicinkliniken, Ljungby Hospital
Study officials:
affiliation: Karolinska Institutet
name: Anna Norhammar, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References: