Heart failure (HF) is a common complication of type 2 diabetes. Unfortunately, there are limited treatment options for glycemic control in patients with HF and diabetes. Although metformin is considered a safe and effective medication, it is currently not recommended in patients who have HF due to a perceived increased risk of lactic acidosis, although there is limited evidence linking metformin to lactic acidosis. Indeed, the near-absence of any cases of lactic acidosis suggests that metformin may be “an innocent bystander” in sick patients rather than a causal agent. We recently completed a large observational study that suggested metformin therapy is associated with lower morbidity and mortality and appears to be safe in this population.

It is important to consider, however, that the currently available evidence supporting the use of metformin in patients with heart failure is based solely on observational data. As a result, we have designed the PHANTOM Study to rigorously assess the safety and efficacy of metformin in a blinded randomized placebo controlled trial (RCT). We are conducting a PHANTOM Pilot Study to evaluate the feasibility of a large RCT in this population and to generate initial morbidity and mortality estimates. The pilot study is being completed a part of a component of Dean Eurich’s PhD dissertation research.

We are aiming for 100 subjects (i.e., approximately 10% of the anticipated number of subjects for a full RCT) who will be randomly assigned to either metformin or matching placebo therapy and followed for 6 months. The primary outcome of the study is a combined endpoint of all-cause mortality and all cause-hospitalization. Secondary endpoints include the individualized components of the primary outcome, development of lactic acid, change in A1c, change in six-minute walk, and change in health related quality of life measures.  We are currently enrolling subjects into the study at the University of Alberta Hospital. It is anticipated that enrollment at the Misericordia Community Hospital and several emergency departments within the Capital Health Region will be commencing within the near future. The results of this pilot study will be used to assess the feasibility of conducting a large multicentre study and to secure funding through various funding agencies, including CIHR and the Heart & Stroke Foundation.

Research Team

Dean Eurich, Richard Lewanczuk, Sumit Majumdar, Finlay McAlister, Ross Tsuyuki, Jeff Johnson

Side Bar comment:
Metformin may be “an innocent bystander” in sicker patients rather than an agent that causes lactic acidosis.