Injection-Site Nodules Associated With Once-Weekly Subcutaneous Administration of Semaglutide

Glucagon-like peptide 1 (GLP-1) receptor agonists are a safe and effective treatment option for patients with type 2 diabetes (1). Selective activation of the GLP-1 receptor causes glucose-dependent insulin secretion, resulting in a very low risk of hypoglycemia (2). The additional mechanism of slowing gastric emptying has resulted in reliable weight loss with this class of antihyperglycemic medications (3). In addition, multiple agents in this drug class (semaglutide, liraglutide, and dulaglutide) have been proven to reduce the risk of cardiovascular events (4).

Furthermore, the possibility of once-weekly dosing for glycemic control in type 2 diabetes has been realized with some GLP-1 receptor agonists (semaglutide, exenatide extended-release, and dulaglutide) as a result of albumin binding that decreases renal clearance and protects against metabolic degradation by the dipeptidyl peptidase-4 enzyme (2). Poor adherence to pharmacologic therapy is well documented in patients with type 2 diabetes and is linked to inadequate glycemic control (based on the American Diabetes Association’s general A1C goal of <7%), and once-weekly dosing has been shown to improve adherence rates (5,6).

The use of GLP-1 receptor agonists in practice has become more prominent in recent years, and adverse reactions are generally benign. Most commonly, patients have reported gastrointestinal upset (>10%) and injection-site reactions (>1%) (1,7).

General injection-site reactions (e.g., erythema, pain, or rash) have been reported with all of the commercially available GLP-1 receptor agonists (i.e., exenatide, lixisenatide, liraglutide, dulaglutide, and semaglutide) (8–13). However, post-marketing reports have revealed that exenatide extended-release, specifically, may cause more alarming injection-site …