Liraglutide (Victoza): A GLP-1 analog approved for the treatment of type 2 diabetes

Liraglutide is the second glucagon-like peptide-1 (GLP-1) analog to gain FDA-marketing approval (January 25, 2010), and is indicated as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus. Exenatide was FDA approved in 2005 and is administered subcutaneously twice daily. A time-released, once-weekly formulation of exenatide is currently under investigation. Current American Diabetes Association (ADA) treatment guidelines list GLP-1 analogs as "Tier 2" agents following metformin, sulfonylureas, and insulin. Thus, GLP-1 analogs such as liraglutide are not recommended as first-line therapy for patients who have inadequate blood sugar control on diet and exercise alone.

Efficacy. Liraglutide was evaluated in The Liraglutide Effect and Action in Diabetes (LEAD) phase 3 trials, one of which was 52 weeks in duration, and the other four lasting 26 weeks. These multinational trials evaluated liraglutide as monotherapy or in combination with 1 or 2 oral hypoglycemic medications. In these trials, liraglutide was found to result in superior lowering of blood glucose than active comparators such as sulfonylureas and thiazolidinediones. Hemoglobin A_1c (HbA_1c) reductions for liraglutide 1.8 mg/d, as monotherapy or in combination with other oral hypoglycemics, ranged from 1.0% to 1.5% across the LEAD trials with baseline HbA_1c values ranging from 8.2% to 8.6%. Liraglutide 1.8 mg/d plus metformin reduced HbA_1c by 1.0% and reduced weight by approximately 6 lbs. Currently, no studies have provided conclusive evidence that liraglutide can reduce the incidence of macrovascular complications (ie, heart attacks).

Safety. The most common adverse reactions reported in patients treated with liraglutide are headache, nausea, diarrhea, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were also more common among liraglutide-treated patients in clinical trials. When liraglutide is used with an insulin secretagogue (eg, a sulfonylurea or glinide) serious hypoglycemia can occur. Healthcare providers should consider lowering the dose of the insulin secretagogue when prescribed concomitantly with liraglutide to reduce the risk of hypoglycemia. Animal studies suggest that liraglutide can cause a dose- and treatment-duration-dependent increase in thyroid C-cell tumors at clinically relevant exposures. Since this increased risk of thyroid cancer could not be ruled out in clinical trials, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with Multiple Endocrine Neoplasia syndrome type 2. Furthermore, patients should be counseled regarding the risk and symptoms of thyroid tumors before receiving liraglutide. In clinical trials, there were more cases of pancreatitis among liraglutide-treated patients than among comparator-treated patients; therefore, it should be used with caution in patients with a history of pancreatitis. If pancreatitis is suspected in patients receiving liraglutide, it should be discontinued. If pancreatitis is confirmed, liraglutide should not be re-initiated.