Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study

Abstract

Background: Long-term treatment is necessary to slow the progression of type 2 diabetes (T2D). Here, we examined the safety and efficacy of 6 years of treatment with exenatide once weekly (QW) among patients with T2D in the DURATION-1 trial.

Methods: The study enrolled patients aged ≥16 years with T2D treated primarily with metformin and sulfonylureas. Following 30 weeks of randomized treatment with exenatide QW 2 mg or exenatide twice daily 10 μg, patients entered an uncontrolled, open-label, open-ended study phase in which all patients received exenatide QW 2 mg. Restrictions on concomitant medication use were eased over time.

Results: Of the original 295 patients in the intent-to-treat population, 136 (46%) completed 6 years of treatment. Six-year completers had sustained significant improvements from baseline in glycated hemoglobin (HbA1c; least-squares mean [LSM] change, -1.6%), with 46.3% achieving HbA1c <7.0%, 33.1% achieving HbA1c ≤6.5%, and significant improvements from baseline in fasting plasma glucose (-28 mg/dL) and body weight (-4.2 kg) at 6 years. The 78 completers who added no glucose-lowering medications had numerically greater body weight reductions than the overall cohort (6-year LSM change, -6.1 kg) with more stability over time. No unexpected adverse events were observed during 1202.4 patient-years of exposure. Most minor hypoglycemia events occurred with concomitant sulfonylurea use.

Conclusions: Exenatide QW was associated with clinically significant, sustained improvements in glycemic control and weight in patients who continued therapy for up to 6 years, without unexpected safety findings. ClinicalTrials.gov registration: NCT00308139.

Conflict of interest statement

Author Disclosure Statement R.R.H. has received research grants from Abbott, AbbVie, and Eli Lilly Pharmaceuticals, has served as a consultant or scientific advisory board member, and received honoraria from Amgen Pharmaceuticals, Boehringer Ingelheim, Eli Lilly Pharmaceuticals, Intarcia, Isis Pharmaceuticals, Ligand, Merck, Novo Nordisk, and Sanofi-Aventis. E.J.K. has received research support from Antares Pharma, Asahi Kasei, AstraZeneca, Bristol-Myers Squibb, Catabasis Pharmaceuticals, and Novo Nordisk, and has served on the speaker's bureau for AstraZeneca and Janssen Pharmaceuticals. J.H. is an employee of Pharmapace, Inc. and was an employee of Bristol-Myers Squibb at the time of data collection. N.I. is an employee of AstraZeneca.

Figures

FIG. 1.

(A) Patient disposition. (B) Kaplan–Meier plot of time to withdrawal and estimates of proportion of patients remaining in study. (C) Kaplan–Meier plot of time to addition of new glucose-lowering medication. (D) Time course of use of the most common concomitant glucose-lowering therapies in 6-year completers (n = 136). Point estimates and 95% confidence intervals for Kaplan–Meier plots were calculated for the time the first event was observed in each year. BID, twice daily; ITT, intent-to-treat; LCL, lower confidence limit; QW, once weekly; UCL, upper confidence limit.

FIG. 1.

(A) Patient disposition. (B) Kaplan–Meier plot of time to withdrawal and estimates of proportion of patients remaining in study. (C) Kaplan–Meier plot of time to addition of new glucose-lowering medication. (D) Time course of use of the most common concomitant glucose-lowering therapies in 6-year completers (n = 136). Point estimates and 95% confidence intervals for Kaplan–Meier plots were calculated for the time the first event was observed in each year. BID, twice daily; ITT, intent-to-treat; LCL, lower confidence limit; QW, once weekly; UCL, upper confidence limit.

FIG. 2.

Key efficacy parameters in all 6-year completers (n = 136) and those not on additional glucose-lowering medications (n = 78). LSM ± SE changes from baseline in (A) HbA1c by ANOVA, (B) FPG, and (C) body weight. *P < 0.05 for change from baseline. ANOVA, analysis of variance; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; LSM, least-squares mean; SE, standard error.

FIG. 2.

Key efficacy parameters in all 6-year completers (n = 136) and those not on additional glucose-lowering medications (n = 78). LSM ± SE changes from baseline in (A) HbA1c by ANOVA, (B) FPG, and (C) body weight. *P < 0.05 for change from baseline. ANOVA, analysis of variance; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; LSM, least-squares mean; SE, standard error.