D.M.N. has received a research grant for investigator-initiated research from sanofi aventis and support for educational programs from GlaxoSmithKline. J.B.B. has conducted research and/or served on advisory boards under contract between the University of North Carolina and Amylin, Becton Dickinson, Bristol-Myers Squibb, Hoffman-LaRoche, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Merck, Novartis, Pfizer, and sanofi aventis. M.B.D. has received research support from Eli Lilly, Merck, and Pfizer; has served on advisory boards for Amylin, GlaxoSmithKline, Merck, and sanofi aventis; and has been on speakers bureaus for Amylin, Eli Lilly, GlaxoSmithKline, and Pfizer. E.F. has received research support from Astra Zeneca, Merck Sharpe & Dohme, and Novartis and serves on scientific advisory boards for Amylin, AstraZeneca, GlaxoSmithKline, Roche, Merck Sharpe & Dohme, Novartis, Servier, sanofi aventis, Boehringer Ingelheim, and Takeda. R.R.H. has received research support from Bristol-Myers Squibb, GlaxoSmithKline, Merck Sante, Novo Nordisk, Pfizer, and Pronova and has served on advisory boards and/or received honoraria for speaking engagements from Amylin, GlaxoSmithKline, Lilly, Merck Sharp & Dohme, Novartis, and sanofi aventis. R.S. has served on advisory boards for Amylin, Astra Zeneca, Boehringer Ingelheim, DiObex, Eli Lilly, Insulet, Merck, MannKind, and Novartis. B.Z. has received research support from GlaxoSmithKline, Merck, Novartis, and Novo Nordisk and has been a member of scientific advisory boards and/or received honoraria for speaking engagements from Amylin, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, sanofi aventis, and Servier.
TITRATION OF METFORMIN
1. Begin with low-dose metformin (500 mg) taken once or twice per day with meals (breakfast and/or dinner) or 850 mg once per day.
2. After 5–7 days, if gastrointestinal side effects have not occurred, advance dose to 850, or two 500 mg tablets, twice per day (medication to be taken before breakfast and/or dinner).
3. If gastrointestinal side effects appear as doses advanced, decrease to previous lower dose and try to advance the dose at a later time.
4. The maximum effective dose can be up to 1,000 mg twice per day but is often 850 mg twice per day. Modestly greater effectiveness has been observed with doses up to about 2,500 mg/day. Gastrointestinal side effects may limit the dose that can be used.
5. Based on cost considerations, generic metformin is the first choice of therapy. A longer-acting formulation is available in some countries and can be given once per day.