The Pattern of Metformin Discontinuation and Reinitiation in US adults with Prediabetes

BackgroundThe American Diabetes Association recommends that metformin may be considered for patients with prediabetes. However, evidence on discontinuation and reinitiation patterns of metformin use in patients with prediabetes remains limited ObjectiveTo describe the rates and specific patient characteristics associated with metformin discontinuation and reinitiation in patients with prediabetes. MethodWe conducted a retrospective observational study using longitudinal electronic health record data from the Truveta database. We identified a total of 23,911 new metformin users with a baseline A1C between 5.7% and less than 6.5% in an incident cohort of prediabetes from January 1, 2019, to May 31, 2025. The pattern of metformin utilization was calculated using linked medication dispensing records within the Truveta network. Treatment discontinuation and reinitiation following the first discontinuation were estimated using the Kaplan-Meier model. Cox proportional hazards regression models were applied to evaluate the association between patient characteristics and treatment discontinuation. ResultIn this retrospective cohort, 14,857 patients (62.13%) discontinued metformin during a maximum follow-up of 6 years. Compared with those who continued treatment, patients who discontinued were more likely to be female (10,137 [68.23%] vs 5,642 [62.31%]), have baseline A1C <6% (5,455[36.72%] vs 2,892 [31.94%]), 60 years or younger (5,190 [57.32%] vs 5,190 [57.32%] ), have baseline class 3 obesity (4,434 [26.7%] vs 2,029 [20.6%]). The median time to discontinuation was 0.82 years (95% CI, 0.79-0.85), with 27.15% of patients discontinuing in 90 days after initiation. The cumulative proportion of discontinuation at 1 year and 2 years was 54.45% (95% CI, 53.77-55.13%) and 69.48% (95% CI, 68.77-70.91%), respectively. The proportion of patients reinitiating metformin after the first discontinuation at 1 year and 2 years was 32.44% (95% CI, 31.64-33.25%) and 41.81% (95% CI, 40.89-42.75%), respectively. The median time to reinitiation was 3.81 years (95% CI, 3.44-4.08) ConclusionMost patients with prediabetes discontinued metformin within the first year, and reinitiation was limited, highlighting gaps in adherence and the need for strategies to optimize metformin use in this population.