Use of Add-on Treatment to Metformin Monotherapy for Patients with Type 2 Diabetes and Suboptimal Glycemic Control: A U.S. Database Study

BACKGROUND: The American Diabetes Association (ADA) recommends metformin to treat individuals diagnosed with type 2 diabetes and recommends that hemoglobin A1c (HbA1c) be maintained below or around 7%. If the HbA1c target is not achieved or maintained by metformin monotherapy at maximal tolerated dose over 3 to 6 months, treatment modification with addition of a second oral antihyperglycemic agent or by initiating insulin is recommended. Despite the importance of attaining and maintaining HbA1c goals, actual treatment behavior may not follow ADA guidelines to add a second oral agent or to initiate insulin as expected even considering that individual patient’s needs are taken into account when treatment decisions are made. OBJECTIVE: To evaluate treatment addition for metformin monotherapy users with suboptimal glycemic control and associated factors. METHODS: A retrospective health care claims study identified 7,109 subjects aged 18 to 89 years, treated for type 2 diabetes with an HbA1c > 7% following at least 60 days of continuous metformin monotherapy. Subjects were required to have 12 months continuous enrollment with the health plan before and after the index lab date. Pharmacological treatment additions after the HbA1c lab result and time to treatment addition were evaluated. A logistic regression model was used to evaluate the patient characteristics and comorbidities associated with the treatment addition. RESULTS: Thirty-eight percent of study subjects had evidence of addition of a second antidiabetic medication to primary metformin monotherapy, 57.5% remained on metformin monotherapy, and 4.5% discontinued metformin altogether. A logistic regression model found age inversely related to treatment addition: age 45-64 versus 18-44 (OR = 0.77, 95% CI = 0.59-0.99) and age 65-89 versus 18-44 (OR = 0.57, 95% CI = 0.43-0.74). HbA1c was positively related to treatment addition: > 8%-9% versus > 7%-8% (OR = 2.31, 95% CI = 2.00-2.67); > 9%-10% versus > 7%-8% (OR = 2.88, 95% CI = 2.32-3.58); and > 10% versus > 7%-8% (OR = 3.54, 95% CI = 2.92-4.28). Evidence of ophthalmic disorder was not related to treatment addition (P = 0.056), but evidence of hypertension (OR = 1.56, 95% CI = 1.28-1.89); hyperlipidemia (OR = 1.28, 95% CI = 1.05-1.55); other cardiovascular diseases (OR = 1.30, 95% CI = 1.16-1.45); obesity (OR = 1.21, 95% CI = 1.08-1.36); and renal disease (OR = 1.35, 95% CI = 1.21-1.51) were associated. CONCLUSIONS: The majority of the metformin monotherapy users with suboptimal glycemic control did not initiate add-on therapy as recommended by guidelines, and prolonged time on metformin monotherapy demonstrated clinical inertia in real-world clinical practice. Several factors were associated with this delay including older age, lower index HbA1c, and lack of evidence of certain comorbidities.