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Long-term exenatide once weekly shows efficacy, tolerability in type 2 diabetes
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Adults with type 2 diabetes initially assigned to the glucagon-like peptide-1 receptor agonist exenatide for 30 weeks saw sustained improvements from baseline levels in HbA1c, fasting plasma glucose and body weight at 6 years, according to findings from an extension of the DURATION-1 study.
“Results of this analysis show that, over 6 years of treatment, patients treated with exenatide [once per week] who remained on therapy demonstrated sustained improvements from baseline in clinical parameters relating to glycemic control, measures of beta-cell function and insulin sensitivity, and cardiovascular risk factors,” Robert R. Henry, MD, of the VA San Diego Healthcare System and the University of California, San Diego, and colleagues wrote. “In addition, a considerable proportion of these patients consistently achieved HbA1c goals, satisfying therapeutic guidelines. These data also showed no new pattern or increased incidence of adverse events over time on therapy.”
Henry and colleagues analyzed data from 136 adults with type 2 diabetes initially assigned to one of two doses of exenatide (Byetta/Bydureon, AstraZeneca) for 30 weeks, followed by an open-ended, open-label extension; original intention-to-treat population included 295 patients. All patients in the extension study were treated with exenatide once weekly, either continuing from the controlled period or switching from exenatide twice daily. Patients returned for follow-up assessments weekly during weeks 31 to 34, again at week 36, at 4-week intervals during weeks 40 to 76 and subsequently at 8-week intervals until study end.
Among 6-year completers, researchers observed improvements in HbA1c from baseline at each annual time point (least squares mean change, –1.6%; 95% CI, –1.8 to –1.4), and with FPG (least squares mean change, –28 mg/dL; 95% CI, –37 to –18). Body weight also improved from baseline at each annual time point and after 6 years (least squares mean change, –4.2 kg; 95% CI, –5.8 to –2.6), as did multiple measures of dyslipidemia, including total cholesterol, LDL, HDL and triglycerides.
Among the 6-year completers who received no additional glucose-lowering medications (n = 78; 57%), reductions in body weight were greater than in the overall cohort (least squares mean change at 6 years, –6.1 kg; 95% CI, –7.5 to –4.6) and more stable over time, according to researchers.
Mild nausea, the most common adverse event reported during the controlled period with weekly exenatide, decreased from 0.846 to 0.076 events per year during the extension period. There were no reported events of major hypoglycemia; most minor hypoglycemia events over 6 years occurred with concomitant sulfonylurea.
“Given the progressive nature of [type 2 diabetes], it would be expected to see indications of disease progression during a study of this duration,” the researchers wrote. “Initial mean improvements in [homeostasis model assessment of beta-cell function] were attenuated over the course of the study, although improvement was still observed with exenatide [once per week] at 6 years. Similarly, increases were observed following the initial mean reduction in FPG, suggesting gradual loss of glycemic control. Although the patients remaining on treatment for 6 years still had progressive [type 2 diabetes], most managed their hyperglycemia without insulin.” – by Regina Schaffer
Disclosure: Amylin Pharmaceuticals initiated this study; AstraZeneca and Bristol-Myers Squibb provided support. Henry reports receiving research grants from and serving as a consultant or scientific advisory board member for Abbott, AbbVie and Eli Lilly Pharmaceuticals, and receiving honoraria from Amgen Pharmaceuticals, Boehringer Ingelheim, Eli Lilly Pharmaceuticals, Intarcia, Ionis Pharmaceuticals, Ligand, Merck, Novo Nordisk and Sanofi-Aventis. Please see the full study for the other authors’ relevant financial disclosures.
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