Efficacy and safety of exenatide once-weekly vs exenatide twice-daily in Asian patients with type 2 diabetes mellitus

Linong Ji, Yukiko Onishi, Chul Woo Ahn, Pankaj Agarwal, Chien-Wen Chou, Harry Haber, Kelly Guerrettaz, Marilyn K Boardman, Linong Ji, Yukiko Onishi, Chul Woo Ahn, Pankaj Agarwal, Chien-Wen Chou, Harry Haber, Kelly Guerrettaz, Marilyn K Boardman

Abstract

Aims/introduction: To compare safety and efficacy of the extended-release formulation exenatide once weekly (EQW) vs exenatide twice daily (EBID) for 26 weeks in type 2 diabetes patients from China, India, Japan, South Korea and Taiwan.

Materials and methods: A randomized, comparator-controlled, open-label study included 681 patients with type 2 diabetes inadequately controlled (hemoglobin A1c [HbA1c] ≥7 and ≤11%) with oral antihyperglycemic medications (OAMs). Patients added 2 mg EQW or 10 μg EBID to current OAMs. Safety was re-evaluated 10 weeks after last treatment.

Results: EQW was superior to EBID on HbA1c measures at week 26 (Least-squares mean treatment difference: -0.31% [95% confidence interval -0.49, -0.14%]). More EQW-treated patients achieved target HbA1c ≤7.0% (P = 0.003), ≤6.5% (P < 0.001), or ≤6.0% (P = 0.003). Fasting serum glucose reductions were greater among EQW-treated patients (P < 0.001). Blood glucose profiles improved in both treatment groups (P < 0.001). Weight loss occurred with both treatments, but was greater with EBID. Adverse events (≥10%, either group) were nausea, injection-site induration, dyslipidemia and vomiting. Injection-site induration was more frequent with EQW, whereas nausea, vomiting and hypoglycemia were less frequent. One episode each of major hypoglycemia (EBID) and pancreatitis (EQW) were reported.

Conclusion: In this population, EQW and EBID showed efficacious glucose and weight control; safety and tolerability were consistent with observations in non-Asian patients. This trial was registered with ClinicalTrials.gov (no. NCT00917267).

Keywords: Asian; Exenatide; Type 2 diabetes.

Figures

Figure 1
Figure 1
Patient disposition and baseline characteristics. Data are mean ± standard deviation, unless otherwise noted. BMI, body mass index; EBID, exenatide twice daily; EQW, exenatide once‐weekly; FSG, fasting serum glucose; HbA1c, hemoglobin A1c; MET, metformin; SU, sulfonylurea; T2D, type 2 diabetes; TZD, thiazolidinedione.
Figure 2
Figure 2
Glycemic parameters in patients treated with oral antihyperglycemic medications plus exenatide once‐weekly (EQW) or exenatide twice daily (EBID). (a) Change in hemoglobin A1c (HbA1c) from baseline at week 26. *P < 0.001, EQW vs EBID. (b) HbA1c values over the course of the study. *P < 0.001, EQW vs EBID. (c) Percentage of patients reaching target HbA1c at week 26. *P = 0.003; **P < 0.001, EQW vs EBID. (d) Change in fasting serum glucose (FSG) from baseline at week 26. (e) Changes from baseline to end‐point on 6‐point self‐monitoring blood glucose profiles. *P < 0.001, EQW vs EBID. LS, least squares; PP, postprandial.
Figure 3
Figure 3
(a) Effects of exenatide once‐weekly (EQW) or exenatide twice daily (EBID) on bodyweight over the 26‐week treatment period. *P < 0.05; *P < 0.001, EQW vs EBID. (b) Scatterplot of change in hemoglobin A1c (HbA1c) vs change in bodyweight from baseline to week 26. LS, least squares.

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