Comparative effectiveness of liraglutide in the treatment of type 2 diabetes

Abstract

Type 2 diabetes is characterized by a progressive decline in beta cell function, with consequent worsening of glycemic control. The ideal antihyperglycemic treatment should achieve good and sustained glycemic control, with a low risk of hypoglycemia and no weight gain. This paper reviews the efficacy and tolerability of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes. Once-daily injection of liraglutide (at doses of 1.2 mg and 1.8 mg), as monotherapy or in combination with one or two oral antihyperglycemic agents, was associated with greater improvements in glycemic control compared with active comparators or placebo in several controlled, randomized Phase III trials, including the six trials of the LEAD (Liraglutide Effect and Action in Diabetes) program. Liraglutide also improved beta cell function, body weight, systolic blood pressure, and lipid profile, thereby achieving many of the goals of ideal antihyperglycemic therapy. Liraglutide was generally well tolerated in the Phase III trials. The most common adverse events were nausea, vomiting, and diarrhea, usually of mild to moderate intensity. The observed rate of pancreatitis was low and comparable with that of the general diabetic population. In conclusion, although most trials were relatively short and focused on surrogate endpoints, liraglutide emerges as an effective and well tolerated treatment for type 2 diabetes, carrying a low risk of hypoglycemia, weight loss, and possible reduction of cardiovascular risk.

Keywords: body weight; cardiovascular; hypoglycemia; incretin.

Figure 1

Summary of the glycemic efficacy of liraglutide in the LEAD program. Notes: Baseline HbA_1c values are shown at the top of each column, with absolute HbA_1c (%) reductions shown at the bottom of each column. *P<0.01 and ***P<0.0001 versus active comparator. Abbreviations: MET, metformin; SU, sulfonylureas; TZD, thiazolidinediones; Sita, sitagliptin; Plb, placebo; HbA_1c, glycosylated hemoglobin; LEAD, Liraglutide Effect and Action in Diabetes program; sita, sitagliptin; Lira, liraglutide; vs, versus; RSG, rosiglitazone.

Figure 2

Schematic representation of the effects of the glucagon-like peptide-1 receptor agonist, liraglutide, in type 2 diabetes. Abbreviation: GI, gastrointestinal.