Saxagliptin Responder Analysis: A Pooled Analysis of 5 Clinical Trials

Objective: To assess the treatment response of patients with T2DM to saxagliptin at 24 weeks based on their initial response to saxagliptin at 12 weeks. Methods: Data were pooled from five 24-week, randomized, placebo-controlled trials of saxagliptin. Patients (N=1994) were categorized by change in glycated hemoglobin (HbA1c) after 12 weeks of saxagliptin treatment as responders (HbA1c decrease ≥ 0.5%; 61% of saxagliptin-treated patients), intermediate responders (HbA1c decrease ≥ 0.2% and <0.5%; 14% of patients), and nonresponders (HbA1c decrease <0.2%; 25% of patients). Results: The adjusted mean change [95% CI] from baseline to week 24 in HbA1c with saxagliptin was greatest in responders (–1.05% [–1.11%, – 0.99%]) followed by intermediate responders (–0.32% [–0.43%, –0.22%]) and nonresponders (0.27% [0.18%, 0.36%]). The proportion of patients achieving HbA1c<7% after 24 weeks was greater in responders (48%) and intermediate responders (41%) versus nonresponders (22%, P<0.0001 for each). The adjusted mean increase from baseline to week 24 in HOMA-2%β was greatest in the responder group (16.9% [13.5%, 20.2%]) compared with the other groups (intermediate responders, 11.7% [5.9%, 17.5%]; nonresponders, 0.4% [–4.8%, 5.6%]). Baseline characteristics that were associated with glycemic response to saxagliptin included higher baseline HbA1c (P<0.0001), higher HOMA-2%β (P<0.0001), lower fasting insulin (P=0.0006), shorter T2DM duration (P=0.033), and male sex (P=0.031). Conclusion: Responders, who comprised 61% of saxagliptin-treated patients analyzed, derived significant benefit from saxagliptin, with a ~1% decline in HbA1c and increased β-cell function at 24 weeks compared with nonresponders.