By: Miriam Maltz, PharmD Candidate c/o 2013, AMSCOP, Long Island University
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia that is pursuant to insulin resistance, defects in insulin secretion, or both1. Chronic hyperglycemia is associated with detrimental effects on various organ systems that can increase mortality and impact the patient’s quality of life; it is therefore crucial to manage these patients appropriately by delaying disease progression and the associated complications of T2DM. Various pharmacotherapeutic options and treatment algorithms are available for the management of T2DM, but each patient needs to receive a regimen that is tailored to their specific glucose goals by examining glucose trends, behavior, risk factors, and much more. A glucose lowering agent that seems promising for the management of T2DM in patients who are obese or at an increased risk of hypoglycemia is liraglutide (Victoza).
Liraglutide is a long acting glucagon-like-peptide-1 (GLP-1) receptor analogue that can be used to improve glycemic control in patients with type 2 diabetes. GLP-1 agonists work at lowering blood glucose by stimulating the release of incretins from the gut. Incretins are hormones that are released from the gut after the ingestion of food; they cause an increase in cAMP and thus a subsequent increase in insulin release from pancreatic beta cells. GLP-1 agonists also contribute to glucose lowering by suppressing glucagon secretion, slowing gastric emptying, and promoting satiety. Conversely, GLP-1 receptor binding is associated with adverse events such as nausea and vomiting which can be avoided if the dose is titrated gradually. The dose of liraglutide is 0.6 mg SC once daily for 1 week which is then increased to 1.2 mg/day. If optimal glucose lowering is not achieved with 1.2 mg/day then the dose can be titrated up to 1.8 mg/day. The 0.6 mg dose does not have glucose lowering effects, rather it is meant to decrease GI symptoms during the initial titration period. The benefits of liraglutide include once daily dosing, weight loss and a low risk of hypoglycemia since liraglutide works on post prandial glucose elevations. Safety concerns include increased risk of pancreatitis and data from studies in rodents found that liraglutide was associated with an increased risk of thyroid C-cell focal hyperplasia and C-cell tumors.
The safety and efficacy of liraglutide was evaluated by the Liraglutide Effect and Action in Diabetes-3 (LEAD-3-Mono) study2 which was a 52 week double-blind, double-dummy, active control trial. According to the results of the study, a greater HbA1c reduction was noted after 52 weeks with liraglutide monotherapy compared to that of glimepiride in patients with T2DM. Glimepiride 8 mg reduced the HbA1c by 0.51% from baseline whereas liraglutide 1.2 mg and 1.8 mg reduced the HbA1c by 0.84% (P= 0.0014) and 1.1% (P < 0.0001) respectively. Investigators also found that patients receiving liraglutide1.8 mg lost on average 3.4 kg after 52 weeks (p<0.0001) compared to patients on glimepiride who conversely gained approximately 1.2 kg (P<0.0001). Additionally, according to the results of a 14 week double-blind, randomized, placebo-controlled trial3 liraglutide at doses of 0.65mg, 1.25 mg. and 1.9 mg was found was more effective at lowering the HbA1c compared to placebo with reductions of 1.74%, 1.69%, and 1.27% respectively (p<0.0001). They also found that in all the treatment groups there was a reduction in body weight; however, weight reduction was only statistically significant in the patients receiving 1.9 mg of liraglutide and they lost an average of 3 kg (P=0.0390).
When comparing liraglutide to traditional first line therapy, such as metformin or sulfonylureas, it is advantageous in respect to its effect on weight loss, low hypoglycemia risk, and its ability to be used in patients with renal dysfunction. However, despite liraglutide’s beneficial effects, current practice guidelines 1-4 do not recommend its use as a first line agent for initial management of T2DM. The downside of liraglutide use is its high cost, unknown long term safety, and its formulation as an injection which requires a patient’s willingness to self-inject. Clinicians need to assess which patients may benefit from liraglutide monotherapy; major considerations include obese patients and patients who are prone to hypoglycemia and cannot tolerate sulfonylureas.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(Suppl 1):S62–S69.
- Garber A, Henry R, Ratner R et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomized, 52 week, phase III, double-blind, parallel-treatment trial. The Lancet. 2009: 373; 473-481.
- Vilsboll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007: 30 (6);1608-10.
- Rodbard HW, Jellinger PS, Davidson JA et al. Statement by AACE/ACE consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocrine Practice. 2009: 15 (6) 1-20.
- Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696–1705.
- Micromedex® Healthcare Series. Greenwood Village, CO. Truven Health Analytics. Accessed December 27, 2012