Initial Choice of Oral Glucose-Lowering Medication for Diabetes Mellitus: A Patient-Centered Comparative Effectiveness Study
Berkowitz SA, Krumme AA, Avorn J, et al
JAMA Intern Med. 2014 Oct 27. [Epub ahead of print]
With All the New Classes of Drugs, Is Metformin Still the First Choice?
This observational cohort study sought to determine the effect of initial oral glucose-lowering class on subsequent need for additional anti-hyperglycemia therapy. Participants included 15,516 patients who were not previously treated for diabetes, in whom therapy with metformin, a sulfonylurea (SU), a thiazolidinedione (TZD), or a dipeptidyl peptidase 4-inihibitor (DPP4) was initiated. The primary outcome was time to treatment intensification, defined as initiation of a different class of oral glucose-lowering medication.
Secondary outcomes included time to composite cardiovascular event (coronary heart disease, congestive heart failure, unstable angina, ischemic stroke, acute myocardial infarction, or a revascularization procedure), congestive heart failure alone, an emergency department visit or hospital admission for hypoglycemia, and any other diabetes-related emergency department visit. The analyses used Cox proportional hazards models with a large number of covariates to adjust for differences in demographic characteristics, comorbidities, and medical utilization.
The Winner, and Still Champion: Metformin
Among the initial group of patients, 58% began therapy with metformin, 23% with an SU, 6% with a TZD, and 13% with a DPP4. During similar median follow-up of slightly more than 1 year, subsequent treatment intensification differed significantly by drug class. Of patients prescribed metformin, 25% required a second oral agent, compared with 37% of SU recipients, 40% of TZD recipients, and 36% of patients taking a DPP4. These results held in multivariable analysis.
Relative to metformin users, the risk for treatment intensification was 68% greater among SU users, 61% greater among TZD users, and 62% greater among DPP4 users. Also relative to metformin, SU use was associated with an increased risk for composite cardiovascular events, congestive heart failure, and hypoglycemia.