In patients with
type 2 diabetes mellitus (T2DM), the physiologic
glucagon-like peptide-1 (GLP-1) response, which is involved in
glucose regulation through several mechanisms, is dysfunctional.
GLP-1 receptor agonists can fill an unmet therapeutic need in the treatment of T2DM: improving
glycemic control without increasing the risk of
hypoglycemia (except with concomitant sulfonylureas) and reducing weight in a substantial proportion of patients.
GLP-1 receptor agonists have impacted established disease treatment algorithms for T2DM. For example, in 2009 the American Diabetes Association and European Association for the Study of Diabetes revised their consensus treatment algorithm to incorporate
GLP-1 receptor agonists.
GLP-1 receptor agonists were originally represented by
exenatide BID (ExBID), a short-acting agent requiring twice-daily
injections at mealtime. The longer-acting agent
liraglutide, requiring once-daily
injections, recently received regulatory approval. Several other long-acting agents are in clinical development, one of which is the once-weekly formulation of
exenatide (
exenatide once weekly [ExQW]). This article reviews the clinical development of ExQW in the DURATION program. Patients in theses clinical trials were receiving various background treatments, ranging from lifestyle
therapy to combination oral
therapy, although the majority (68%) received
metformin monotherapy. Specifically, safety,
glycemic control, and weight were compared in patients treated with ExQW versus ExBID,
sitagliptin,
pioglitazone, or
insulin glargine. Moreover, measures of β-cell function, cardiovascular risk,
inflammation, and hepatic health were investigated. During ExQW clinical development, consistent clinical efficacy (
glycosylated hemoglobin, -1.5% to -1.9%; weight, -2 kg to -4 kg) and safety data were observed in patients with T2DM treated with ExQW.