Four-Year Durability of Initial Combination Therapy with Sitagliptin and Metformin in Patients with Type 2 Diabetes in Clinical Practice; COSMIC Study

OBJECTIVES: We investigated the efficacy of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes for 4 years in clinical practice. METHODS: Between 2009 and 2010, we reviewed 1,178 patients with type 2 diabetes (HbA(1c )≥7.5% or 58 mmol/mol) prescribed initial combination therapy with sitagliptin and metformin. After excluding 288 patients without a second follow-up, 890 individuals (age, 58.0 ± 12.5 years; BMI, 25.4 ± 3.5 kg/m(2); HbA(1c), 8.6 ± 1.1%) were followed up with every 3–6 months for 4 years. Homeostasis model assessments for insulin resistance and β-cell function (HOMA-β) were recorded at baseline. The response criterion was HbA(1c) reduction by ≥0.8% from baseline or attainment of the target HbA(1c) (≤7.0% or 53 mmol/mol). At the end of every year of treatment, changes in HbA(1c) from the baseline were assessed. RESULTS: After 1 year, 72.2% of patients with initial combination therapy had responded, defined as HbA(1c) reduction ≥0.8% or attainment of the target HbA(1c )≤7.0%. After 4 years, 35.4% of the patients still showed a response, with an HbA(1c) level of 7.0 ± 0.9%. A high HbA(1c) level at baseline was the most significant independent predictor of the long-term response (P<0.001). In addition, low HOMA-β was a significant predictor of a greater reduction in HbA(1c). This treatment was generally well tolerated over the 4-year follow-up period, without any serious adverse events. CONCLUSIONS: This real-world follow-up study shows a persistent glucose-reducing effect of initial combination therapy with sitagliptin and metformin for up to 4 years.