Progression through diabetes therapies among new elderly users of metformin: a population-based study.

AIMS: To examine temporal changes in progression to second-line therapies among older patients with diabetes newly treated with metformin. METHODS: We conducted a population-based study among residents of Ontario, Canada aged 66 years and older with diabetes newly treated with metformin monotherapy in 1997, 2000, 2003 or 2006. Each annual cohort was followed until progression to a second oral hypoglycaemic agent, insulin or until 31 December 2010. Time to progression to a second oral hypoglycaemic agent or insulin was compared across the cohorts. RESULTS: In the four annual cohorts, we identified a total of 46 104 people newly treated with metformin monotherapy. The median time to progression to any second diabetes therapy lengthened significantly over time, from 5.0 years in 1997 to 6.1 years in 2003 (P < 0.0001). Similarly, the time to progression to insulin lengthened over the study period (P = 0.03). Furthermore, the choice of second-line therapy changed over time. While 80.7% of new metformin users in 1997 progressed to glyburide therapy as second-line treatment, the corresponding figure by 2006 was only 45.1% as newer treatment options emerged. CONCLUSIONS: Although recent guidelines recommend aggressive intensification of oral therapy for patients with Type 2 diabetes, older Ontarians with diabetes who started metformin in 2006 remained on monotherapy for longer than those who started in 1997. Furthermore, although there is no consensus regarding a preferred second-line therapy, the introduction of new alternatives has led to greater variation in the selection of second-line therapies in this population.

A population-based assessment of the drug interaction between levothyroxine and warfarin.

Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case-control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67-1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine-warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification.