Metformin and insulin: Is there a role for combination therapy?

OBJECTIVE: TO review the literature on concomitant insulin and metformin therapy in patients with type 1 diabetes to determine the potential for combination therapy. DATA SOURCES: A MEDLINE and bibliographic search (1966-1996) of the literature pertaining to metformin and phenformin and their combined use with insulin in the treatment of patients with type 1 diabetes mellitus was performed. STUDY SELECTION: All human studies using metformin with insulin were included in the analysis. Studies using phenformin with insulin were also included due to its similarities to metformin. DATA SYNTHESIS: The recent availability of metformin provides some new options for treating diabetes mellitus. One possibility is the use of this medication in conjunction with insulin in patients with type 1 diabetes. Although this seems like a potentially beneficial combination, there is currently no recommendation for use in this manner. Experience with combination metformin and insulin therapy has consistently demonstrated a reduction in insulin requirements. Studies have not been of necessary size or duration to definitively prove the benefits of this insulin dose reduction or any other benefits of combination therapy. CONCLUSIONS: When metformin is added to insulin therapy, insulin requirements are likely to decrease. Although one would anticipate benefits from reduction in circulating insulin concentrations, the studies do not provide data to determine if benefits of combination therapy outweigh risks. Further studies of larger size and longer duration are needed before the use of metformin with insulin can be routinely recommended in patients with type 1 diabetes.