International guidelines recommend metformin as initial pharmacotherapy for patients with type 2 diabetes (T2D). Guidelines recommend metformin is up-titrated to a maximally effective (~2000 mg/day) dose based on glycemic control and tolerability; however, the extent to which this dose titration occurs in the real-world setting is unknown. To address this question in a U.S. population, we conducted a retrospective cohort study using the Optum database to evaluate the dose distribution of metformin monotherapy (MM) over 12 months in adult (≥21 years) T2D patients initiating MM during 2013-2016. Of the 30,352 eligible patients, 49% were female and median age was 65 years. The Table describes the distribution of metformin dose over the 12-month follow-up period. The majority (88%) of patients were initiated on MM at ≤1000 mg/day. At 3, 6 and 12 months, 84%, 82% and 80% of MM patients, respectively, were on doses ≤1000 mg/day. At 12 months, only 16% of patients were on a metformin dose >1500 mg/day. Among those who were up-titrated during follow-up (n=5003), the median highest dose of metformin was 1500 mg/d and median time to highest dose was 165 days.
In conclusion, the majority of MM patients were not up-titrated and remained on a sub-maximally effective dose of metformin at 12 months despite international guidelines. Further research will be conducted to examine the relationship between MM dose and glycemic control.
K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. B. Sawhney: Consultant; Self; Merck & Co., Inc. S. Rajpathak: None. M. Crutchlow: Consultant; Spouse/Partner; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Self; Merck & Co., Inc. Research Support; Spouse/Partner; Dexcom, Inc. G. Fernandes: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited.
