Critical appraisal of once-weekly formulation of exenatide in the control of type 2 diabetes mellitus

Abstract

Exenatide (also known as exendin-4) is a glucagon-like peptide-1 mimetic, which is indicated for the treatment of type 2 diabetes mellitus. The currently available formulation of this drug is a twice-daily exenatide (exenatide BID) injection that should be administered within 60 minutes of food. Once-weekly exenatide (exenatide QW) formulation is now being assessed in a clinical trial program. Exenatide QW has been shown to be the only noninsulin monotherapy to achieve glycosylated hemoglobin levels of <7% in >75% of treated patients. It has also demonstrated potential cardiovascular benefits by lowering total and low-density lipoprotein cholesterol concentrations, triglyceride levels, and both systolic and diastolic blood pressure. In addition, patients treated with exenatide QW achieved significant weight loss, which may also lead to significant cardiovascular risk reduction. Exenatide QW is associated with a lower incidence of gastrointestinal adverse effects compared with exenatide BID, and no patients treated with exenatide QW monotherapy experienced a confirmed hypoglycemic event. Exenatide QW results in 24-hour coverage with exenatide concentrations that are known to improve glycemic control and remain well tolerated in patients with type 2 diabetes mellitus. This review defines the state of play with exenatide QW by critically appraising its role in clinical practice.

Efficacy and tolerability of exenatide twice daily and exenatide once weekly in Asian versus White patients with type 2 diabetes mellitus: A pooled analysis

“…Selected exenatide BID studies included those with a minimum treatment duration of 12 weeks, whereas for exenatide QW, the minimum duration was 24 weeks. Because of the immediate onset of drug action with exenatide BID, a minimum study duration of 12 weeks was considered sufficient for HbA1c changes to be detected [43]. With exenatide QW, however, steady-state drug concentration is not reached until 6 to 8 weeks after initiation, thus longer times on therapy were considered necessary to achieve detectable reductions in HbA1c [44].…”

Emerging utility of once-weekly exenatide in patients with type 2 diabetes

“… 4 Exenatide is a 39-amino acid peptide that shares 53% of its amino acid sequence identity with human GLP-1, and both have common glucoregulatory actions. 5 Due to its pharmacological resemblance to native GLP-1, exenatide binds to and activates GLP-1 receptors, resulting in actions similar to native GLP-1 and reduces both fasting and prandial glucose levels. 5 The pharmacokinetics of exenatide, although longer than native GLP-1, still requires twice-daily dosing.…”

“… 5 Due to its pharmacological resemblance to native GLP-1, exenatide binds to and activates GLP-1 receptors, resulting in actions similar to native GLP-1 and reduces both fasting and prandial glucose levels. 5 The pharmacokinetics of exenatide, although longer than native GLP-1, still requires twice-daily dosing. To overcome this short half-life, a long-acting depot formulation of exenatide was developed in 2003.…”