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Observational Study
. 2015 Jun 12;10(6):e0129477.
doi: 10.1371/journal.pone.0129477. eCollection 2015.

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

Eu Jeong Ku  1 , Kyong Yeon Jung  2 , Yoon Ji Kim  2 , Kyoung Min Kim  2 , Jae Hoon Moon  2 , Sung Hee Choi  2 , Young Min Cho  3 , Kyong Soo Park  3 , Hak Chul Jang  2 , Soo Lim  2 , Bo Ahrén  4
Affiliations
Observational Study

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

Eu Jeong Ku et al. PLoS One. .

Abstract

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 (HbA1c ≥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/m2; HbA1c, 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 HbA1c reduction by ≥0.8% from baseline or attainment of the target HbA1c (≤7.0% or 53 mmol/mol). At the end of every year of treatment, changes in HbA1c from the baseline were assessed.

Results: After 1 year, 72.2% of patients with initial combination therapy had responded, defined as HbA1c reduction ≥0.8% or attainment of the target HbA1c ≤7.0%. After 4 years, 35.4% of the patients still showed a response, with an HbA1c level of 7.0 ± 0.9%. A high HbA1c 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 HbA1c. 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.

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Conflict of interest statement

Competing Interests: B.A. has consulted for and/or received lecture fees from Novartis A/S, GlaxoSmithKline, Merck, Sanofi, Boehringer Ingelheim, Bristol-Myers Squibb/AstraZeneca, Takeda, and Novo Nordisk. Y.M.C. received a lecture fee or consultation fee from MSD, Lilly, Novartis, AstraZeneca, and Boehringer Ingelheim. Other authors have no conflicts of interests to disclose. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Study disposition.
FU; follow-up.
Fig 2
Fig 2. Comparison of HbA1c levels for 48 months between responders (n = 315) and nonresponders (n = 42) when response was defined as ≥0.8% of HbA1c reduction from baseline or attainment of target HbA1c (≤7.0%) at the end of 4 years’ follow-up.
* P < 0.001 for responder vs. nonresponder group.
Fig 3
Fig 3. Reduction in HbA1c (%) after 3 months in long-term responders and early nonresponders.
Fig 4
Fig 4. Changes in HbA1c (%) after initial combination therapy with sitagliptin and metformin according to the tertiles (T) of HOMA-IR and HOMA-β at baseline.
HOMA-IR and HOMA-β; homeostasis model assessment of insulin resistance and β-cell function. Logarithmically transformed values of HOMA-IR and HOMA-β were used for analyses. Log (HOMA-β) tertiles; T1 ≤3.65, 3.66 ≤T2 ≤4.17, T3 ≥4.18. * P<0.001, † P<0.05.
See this image and copyright information in PMC

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