The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naïve patients with type 2 diabetes mellitus: a randomized controlled trial

Abstract

Background: The aim of this study was to assess efficacy and safety of saxagliptin monotherapy for up to 76 weeks in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control, with main efficacy assessment at 24 weeks.

Methods: 365 treatment-naïve patients with T2DM (HbA1c 7.0%-10.0%) were treated with saxagliptin 2.5 mg q.A.M., saxagliptin 2.5 mg q.A.M. with possible titration to saxagliptin 5 mg, saxagliptin 5 mg q.A.M., saxagliptin 5 mg q.P.M., or placebo. After week 24, patients in all groups were eligible for titration to saxagliptin 10 mg based on HbA1c ≥7%, and all unrescued placebo patients began blinded metformin 500 mg/day. Rescue with open-label metformin was available for patients with inadequate glycemic control.

Results: At week 24, placebo-subtracted mean HbA1c reduction from baseline (LOCF) was significantly greater in the saxagliptin treatment groups vs placebo, and remained greater through week 76. Serious adverse events (AEs) and discontinuations due to AEs were similar in saxagliptin and control groups; incidence of confirmed hypoglycemia was low across all treatment groups (saxagliptin-treated, 2 [0.7]; control, 1 [1.4]).

Conclusions: In treatment-naïve patients with T2DM, saxagliptin monotherapy demonstrated statistically significant improvement in HbA1c compared with placebo at 24 weeks and was generally well tolerated for up to 76 weeks.

Trial registration: ClinicalTrials.gov Identifier: NCT00316082.

Figure 1

Patient disposition short-term period (week 24) and long-term extension (week 76). Rescued patients include all patients who were rescued in short-term period or long-term extension period. Rescued patients may later have discontinued from the study.*One patient did not enter lead-in period but was directly randomized to double-blind treatment. ^†One patient in the saxagliptin 5 mg q.P.M. group and one patient in the placebo group completed week 24, but discontinued treatment (lost to follow-up and poor compliance, respectively).

Figure 2

Adjusted mean changes from baseline HbA_1c over 76 weeks (repeated-measures analysis). Randomized and treated patients. Patients who received placebo in the short-term period were switched to blinded metformin 500 mg at week 24. Titration of blinded metformin was not allowed. BL: baseline; HbA_1c: glycated hemoglobin; PBO: placebo; SAXA: saxagliptin.