Up-titration and distribution of dose of metformin monotherapy in the real-world

Date of ISAC Approval: 
Lay Summary: 
Metformin is often the first medication prescribed for managing patients with type 2 diabetes mellitus (T2DM). After treatment initiation, clinical guidelines recommend increasing the dose of metformin over a couple of months to the highest tolerable dose. However, there are limited data available on how the dose of metformin is modified in the real world and the distribution of dose among patients on metformin therapy. The current study will examine the dose of metformin prescribed to patients with T2DM, determine whether the initial dose of metformin is increased, and assess how long it takes patients to reach their highest dose of metformin.
Technical Summary: 
In order to assess metformin dose and up-titration patterns, the current study will identify T2DM patients >/=21 years from the CPRD database with a prescription for metformin monotherapy between Jan-2017 and Dec-2017 for prevalent users and Jan-2013 to Dec-2016 for new users. The index date for prevalent users is the last metformin prescription during the period and for new users it is the first prescription. All users need to have continuous enrolment in the database one year prior to the index date. New users need continuous enrolment in the database for 15 months following the index date. This study will investigate the distribution of metformin dose in the real world among prevalent users. Among new users, it will describe the distribution of dose at initiation, 3, 6 and 12 months, the proportion of patients who up-titrate therapy at each time point, and the time to highest dose of metformin among those who up-titrate. Data will be censored if patients discontinue metformin or add another diabetes medication during follow-up. Measures of central tendency and dispersion for continuous variables and frequency/percentages for categorical variables will be reported. Cumulative incidence function will be used to estimate time to up-titration for new users
Health Outcomes to be Measured: 
- Metformin dose distribution - Goal attainment - Time to add-on therapy - Up-titration of metformin dose - Sociodemographic and clinical factors associated with up-titration - Time to highest dose of metformin - Treatment intensification (i.e., add-on therapy)

Kristy Iglay - Chief Investigator - Merck & Co., Inc.
Alex Z. Fu - Collaborator - CHEORS
Baanie Sawhney - Collaborator - CHEORS
Gail Fernandes - Collaborator - Merck & Co., Inc.
Professor Kamlesh Khunti - Collaborator - University Of Leicester
Kristy Iglay - Corresponding Applicant - Merck & Co., Inc.
Michael Crutchlow - Collaborator - Merck & Co., Inc.
Swapnil Rajpathak - Collaborator - Merck & Co., Inc.