The study will investigate metformin and the prevention of cardiovascular events in patients with acute myocardial infarction and newly detected prediabetes.
Conditions
Interventions
Trade Name: Metformin
Pharmaceutical Form: Coated tablet
INN or Proposed INN: METFORMIN
CAS Number: 657-24-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2000-
Sponsors
Karolinska Institutet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I. AMI II. Swedish citizens with a personal ID number =18 years and =80 years III. Newly diagnosed prediabetes: a. HbA1c 42-47 mmol/mol or b. Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or c. 2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or d. 2-hour post-load venous plasma glucose concentration 7.8-11.0 mmol/L e. HbA1c 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, only revealed by OGTT) IV. Naïve to metformin and other glucose lowering therapy V. Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3160
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate if metformin compared to standard care has beneficial effects on the occurrence of a composite CV endpoint (all-cause mortality, MI, heart failure or stroke) in patients with AMI and newly detected prediabetes or isolated post-load glucose diabetes levels (identified by oral glucose tolerance test [OGTT], HbA1c or fasting glucose levels).;Secondary Objective: To determine if metformin compared to standard care has beneficial effects on the occurrence of specific CV and non-CV events in patients with AMI and newly detected prediabetes. Safety objectives To assess the safety in using metformin by registering number of SAEs with at least a possible relationship to the study medication, and to collect all registered cases of hospitalisation for lactic acidosis and hospitalisation for severe hypoglycaemia. ;Primary end point(s): Time to major CV event defined as a composite endpoint of first of all-cause mortality or main diagnosis of MI, heart failure or stroke (reported in SWEDEHEART, the National Patient Register and the Cause of Death Register).;Timepoint(s) of evaluation of this end point: Each patient will be followed until the 24 month visit, data on events will continuously be collected during this time and at the patient´s end of study, no data on events after the patient’s end of study will be collected. The primary and secondary endpoints will be collected from SWEDEHEART (RIKSHIA and SEPHIA) and national registries (the National Patient Register, the Cause of Death Register and the Prescribed Drug Register). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to first event included in the composite endpoint of CV mortality, main diagnosis of MI, heart failure or stroke. CV mortality is defined as underlying CV cause of death in the cause of death register (I00-I99). MI, heart failure and stroke as defined in the primary endpoint detailed in 6.1. 2. Time to first event included in the composite endpoint of all-cause mortality, main diagnosis of MI, stroke and revascularisation (CABG or PCI >4 months after the index AMI). Coronary revascularisation is defined as CABG or PCI in the national patient register (Z95, FNA-FNE, FNG). 3. Time to all-cause mortality 4. Time to CV mortality 5. Time to hospitalisation with MI 6. Time to hospitalisation with stroke 7. Time to hospitalisation with heart failure. 8. Time to new cancer diagnosis. Cancer is defined as the first occurrence of any cancer in the National Patient Register (C00-97). 9. Time to initiation of any glucose lowering therapy, ATC code A10 in the Prescribed Drug Register, excluding randomisation to metformin (ATC code A10BA02) in the active treatment arm. 10. Time to diabetes diagnosis. Defined as ICD code E10-E11 in National Patient Register and/or ATC code A10 in the Prescribed Drug Register excluding randomisation to metformin (ATC code A10BA02) in the active treatment arm. 11. Analyses of primary and secondary endpoints including all available registry follow-up for all patients at end of trial. These analyses will include about 2-4 years of follow-up for each patient, where the first two years are under protocol-guided treatment within the trial. Safety endpoints 1. Serious Adverse Events with at least a possible relationship to the study medication 2. Lactic acidosis (E11.1D). 3. Hypoglycaemia (E11.0C, E11.6A, E15.9, E16.0-E16.2). Lactic acidosis and hypoglycaemia are collected from the National Patient Register and eCRF Long term follow up Analyses of primary and secondary endpoints in | — |
Countries
Sweden
Contacts
Public ContactDepartment of medicine
Karolinska Institute
Outcome results
None listed