Sitagliptin compared with thiazolidinediones as a third-line oral antihyperglycemic agent in type 2 diabetes mellitus

Abstract

Objective: To compare sitagliptin and thiazolidinediones as third-line oral antihyperglycemic agents among ethnic minority patients with poorly controlled type 2 diabetes mellitus.

Methods: In an open-label, single-arm design, we treated type 2 diabetic patients who had suboptimal diabetes control on maximum tolerated dosages of metformin plus sulfonylureas with the addition of sitagliptin, 100 mg daily, and compared their responses with findings from a historical control group of similar patients treated with rosiglitazone, 8 mg daily, or pioglitazone, 45 mg daily, as their third-line oral agent. Patients were assessed bimonthly, and those who achieved hemoglobin A1c levels less than 7.5% at 4 months continued through 1 year of follow-up.

Results: One hundred eight patients were treated with sitagliptin, and 104 patients constituted the historical control group treated with rosiglitazone or pioglitazone. At baseline, sitagliptin- and thiazolidinedione-treated patients had identical hemoglobin A1c levels (mean ± SD) (9.4 ± 1.8% and 9.4 ± 1.9%, respectively) and similar known diabetes duration (6.7 ± 5.0 years and 7.6 ± 5.8 years, respectively). Hemoglobin A1c was reduced in both groups at 4 months (P<.001), but the reduction was greater with thiazolidinediones than with sitagliptin (-2.0 ± 1.7% vs -1.3 ± 1.8%; P = .006), as was the proportion of patients achieving a hemoglobin A1c level less than 7.5% (62% vs 46%; P = .026). Of all patients achieving a hemoglobin A1c level less than 7.5% at 4 months, the same proportions in each group sustained their hemoglobin A1c level less than 7.5% by 12 months (59% vs 58%). Sitagliptin was well tolerated.

Conclusions: Among ethnic minority patients with poorly controlled type 2 diabetes while taking maximum tolerated dosages of metformin and sulfonylureas, third-line add-on therapy with a thiazolidinedione controlled hyperglycemia more effectively than sitagliptin after 4 months.

Trial registration: ClinicalTrials.gov NCT00686634.

Conflict of interest statement

DISCLOSURE

The entire study was investigator initiated, and its concept, design, conduct, analyses, presentation, and manuscript preparation were all under the exclusive control of the authors at all times. Other than supplying sitagliptin, Merck & Co, Inc, had no involvement with the design, conduct, analyses, or manuscript preparation for this study. This study was registered with Clinicaltrials.gov (NCT00686634). The authors have no multiplicity of interest to disclose.

Figures

Fig. 1

Flowchart of all sitagliptin-treated patients. aIncluded 11 patients with last observation at 2 months carried forward (hemoglobin A1c paradoxically increased and patients were given alternative therapy). bIncluded 2 patients with last observation at 10 months carried forward (hemoglobin A1c level sustained at less than 7.5%, but they did not attend the 12-month visit).

Fig. 2

Hemoglobin A1c (HbA1c) responses at 4 months for sitagliptin- and thiazolidinedione (TZD)-treated patients. Dotted line indicates the hemoglobin A1c threshold of 7.5%. Solid dashes indicate the mean HbA1c levels for each group at baseline and 4 months.