Efficacy and safety of autoinjected exenatide once‐weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION‐NEO‐2 randomized clinical study

Abstract

AimsGlucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors treat type 2 diabetes through incretin‐signaling pathways. This study compared the efficacy and safety of the glucagon‐like peptide‐1 receptor agonist exenatide once‐weekly (Miglyol) suspension for autoinjection (QWS‐AI) with the dipeptidyl peptidase‐4 inhibitor sitagliptin or placebo.Materials and methodsIn this open‐label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0 mg QWS‐AI, sitagliptin 100 mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28 weeks.ResultsAt 28 weeks, exenatide QWS‐AI significantly reduced HbA1c from baseline compared to sitagliptin (−1.13% vs −0.75% [baseline values, 8.42% and 8.50%, respectively]; P = .02) and placebo (−0.40% [baseline value, 8.50%]; P = .001). More exenatide QWS‐AI‐treated patients achieved HbA1c <7.0% than did sitagliptin‐ or placebo‐treated patients (43.1% vs 32.0% and 24.6%; both P < .05). Exenatide QWS‐AI and sitagliptin reduced fasting plasma glucose from baseline to 28 weeks (−21.3 and −11.3 mg/dL) vs placebo (+9.6 mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (−1.12 and −1.19 kg), but not with placebo (+0.15 kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS‐AI were gastrointestinal events and injection‐site reactions.ConclusionsThis study demonstrated that exenatide QWS‐AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.

Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension

“…Exenatide QW was available as a vial and syringe (single‐dose tray), or as a single use prefilled pen injector; however, both presentations required patients to mix exenatide‐containing microspheres and aqueous diluent prior to the injection. So as to improve the convenience of use prior to injection, exenatide QW suspension (QWS) was developed for use with an autoinjector device, in which the microspheres are suspended in 0.774 g Miglyol 812, a mixture of medium chain triglycerides (MCTs), in a 2 mg dose of exenatide QWS (Gadde, Vetter, Iqbal, Hardy, & Ohman, ; LaRue & Malloy, ). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFA; Gadde et al, ).…”

“…So as to improve the convenience of use prior to injection, exenatide QW suspension (QWS) was developed for use with an autoinjector device, in which the microspheres are suspended in 0.774 g Miglyol 812, a mixture of medium chain triglycerides (MCTs), in a 2 mg dose of exenatide QWS (Gadde, Vetter, Iqbal, Hardy, & Ohman, ; LaRue & Malloy, ). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFA; Gadde et al, ). The fatty acids in MCTs are caproic acid (C6), caprylic acid (C8), capric acid (C10) and lauric acid (C12).…”

Treatment satisfaction with ITCA 650, a novel drug‐device delivering continuous exenatide, versus twice‐daily injections of exenatide in type 2 diabetics using metformin

“…Among the newer classes of anti‐hyperglycaemic agents approved in the USA is exenatide, the first‐in‐class glucagon‐like peptide 1 (GLP‐1) receptor agonist. Multiple studies have demonstrated the efficacy of exenatide in controlling blood glucose levels and in promoting weight loss, with known side effects of nausea and/or vomiting (N/V) . All currently marketed formulations of exenatide and other GLP‐1 receptor agonists are administered by injection.…”

Corrigendum

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In Gadde et al [1], on page 981, in the section 2.6 Statistical Analysis, second paragraph in second column contained some missing text. The paragraph should have read:

The primary endpoint was assessed using a mixed-effects model repeated measures (MMRM) with change in HbA1c as the dependent variable; treatment, week of visit, treatment-by-week interaction, screening HbA1c stratum and screening HbA1c stratum-by-week interaction as fixed effects; and patient as random effect.

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“…In Gadde et al [1], on page 981, in the section 2.6 Statistical Analysis, second paragraph in second column contained some missing text. The paragraph should have read:…”