Insights from the Liraglutide Clinical Development Program—the Liraglutide Effect and Action in Diabetes (LEAD) Studies

Standard therapies for type 2 diabetes often fail to maintain glycemic control over the long term, in part because they do not target the underlying cause. Current treatments may also be associated with weight gain, hypoglycemia, and other adverse effects, and can be difficult to use. Disease progression is accompanied by a progressive decline in beta-cell function, which begins early in the disease course, and an impaired incretin response. The recently developed glucagon-like peptide-1 (GLP-1) receptor agonists overcome some of the limitations of conventional treatments. This article summarizes the key results of the new GLP-1 receptor agonist (liraglutide) phase 3 Liraglutide Effect and Action in Diabetes (LEAD) studies. This series of 6 randomized controlled studies involved > 4400 patients with type 2 diabetes who were unable to maintain glycemic control with diet and exercise alone or with oral treatment, approximately 2700 of whom received liraglutide. The studies demonstrated the efficacy and safety of liraglutide both as monotherapy and as combination therapy with 1 or 2 oral agents. In addition to providing robust glycemic control in these studies, liraglutide reduced weight in most patients, improved beta-cell function, lowered blood pressure and triglycerides, and was well tolerated with minimal risk of hypoglycemia.