Outcomes and Treatment Patterns of Adding a Third Agent to 2 OADs in Patients with Type 2 Diabetes

BACKGROUND: Patients with uncontrolled type 2 diabetes mellitus (T2DM), despite therapy with 2 oral antidiabetic drugs (OADs), may add a third OAD or a glucagon-like peptide-1 receptor agonist (GLP-1) or initiate insulin therapy. The transition to insulin has been shown to be delayed in current practice, potentially through clinical inertia—the failure of health care providers to initiate or advance therapy when indicated. Patients and physicians may be resistant to insulin therapy because of beliefs about side effects and limitations to patients’ lifestyle, while patients may consider that starting injectable therapy signifies a considerable worsening of their disease and may feel they have “failed” to manage it effectively. OBJECTIVES: To describe current treatment patterns and outcomes among adult patients with T2DM in the United States who were treated with 2 OADs and added a third antidiabetic drug. METHODS: This retrospective study followed patients with T2DM who added a third OAD (the “3OAD” cohort), insulin (“+Insulin”), or a GLP-1 (“+GLP-1”) between July 2000 and March 2009. Patients were followed for up to 2 years. Baseline characteristics and follow-up outcomes—including blood glucose level (HbA1c), hypoglycemia, and health care costs—were examined. Treatment persistence was assessed to determine how long patients continued with their prescribed medications without discontinuing or switching. RESULTS: A total of 51,771 patients adding a third agent to their 2OAD regimen were included in this study. Most patients added a third OAD (n = 41,052) over insulin (n = 6,904) or GLP-1 (n = 3,815). At baseline, +Insulin patients were older, with higher comorbidity burden and higher HbA1c. During follow-up, 3OAD patients were more likely to be persistent with their treatment than +Insulin or +GLP-1 patients, but +Insulin patients had the greatest HbA1c reduction from baseline, while continuing with insulin treatment was associated with higher HbA1c reduction. Among 3OAD patients, most of those who switched a third agent initiated insulin, and those who switched early during the follow-up period had greater HbA1c reduction than those who continued with the 3OAD treatment regimen. Average annual health care costs declined in +Insulin patients but increased among 3OAD and +GLP-1 patients. Treatment persistence and HbA1c reduction in +GLP-1 patients were low. CONCLUSIONS: This study found that in current practice, physicians seem to be reluctant to prescribe injectable agents for patients with uncontrolled T2DM despite combination OAD therapy. Despite higher treatment persistence among patients adding a third OAD, this persistence did not translate into better glycemic control and may not necessarily be a long-term cost-saving solution. These data indicate a need for more evidence-based and patient-centered treatment decisions for patients unable to achieve and maintain glycemic targets on multiple OADs.