Can metformin be safely used in patients with heart failure?

Metformin hydrochloride (oral tablet immediate release formulation). This study is both observational and interventional. The observational segment (Study A and Study B) will provide a platform for the safe intervention in Study C. Study A and Study B: Firstly, Study A, a cross-sectional survey will be conducted of patients with T2DM and heart failure, already on metformin. If the patient consents (patient information and consent form), one whole blood sample (4 mL) will be collected at the screening visit. This will be used to test for metformin concentrations, lactate concentrations, NT-ProBNP, biochemical parameters and genetic polymorphisms of transporters involved in the uptake and secretion of metformin. Secondly, Study B, a cross-sectional survey will be conducted of patients without T2DM and heart failure, not on metformin. If the patient consents (patient information and consent form), one whole blood sample (4 mL) will be collected at the screening visit to analyse only NT-ProBNP and lactate concentrations. In both Study A and B the patients will be recruited at the time of a clinic visit, for one visit only. Study C - This section involves a larger interventional clinical trial dosing metformin in patients with heart failure, no T2DM and not already taking metformin. At the screening visit the patient’s demographics, medical conditions and current treatments will be recorded. The patients will also undergo a medical examination and blood collection for the determination of baseline plasma metformin concentrations to check that the patient is not currently taking metformin. Additionally, if the patient consents (separate patient information and consent form), one whole blood sample (4 mL) will be collected at the screening visit. This will be used to test for genetic polymorphisms of transporters involved in the uptake and secretion of metformin. Patients will start a low dose of metformin (500 mg once daily). The dose of metformin will be increased after 3 days to 1000 mg per day (500 mg twice daily) for 12 weeks. A patient diary will also be given to patients to record the times of drug administration for the entire study period. Patients will attend study visits (for blood collection) at week 2, 4, 6, 8 and 12 after initiation of metformin dosing to monitor their on-going safety whilst on metformin. Blood collected at each of the study visits will be used to determine the same parameters as listed above. In addition, HbA1c will be assessed at weeks 8 and 12. The study doctors will review and sign off on all blood results from each patient. Any abnormal blood results will be followed up at an additional study visit in order to more closely monitor the patient’s safety. Patients will also have an opportunity to report any adverse effects they may be experiencing and/or any other concerns they may have at each study visit. The procedures for the exit visit are the same for the screening visit as described above (with the exclusion of the metformin prescription). Patients will be asked to return any remaining tablets of metformin as well as their study diary at the exit visit.