Glucagon-like peptide-1 receptor agonists provide good glycemic control and weight loss in patients with type 2 diabetes mellitus. Because of its large molecular weight, it has low permeability in the gastrointestinal tract and is liable to enzymatic degradation in the stomach. As a result, only an injectable formulation was developed and launched into the market. In recent years, however, an oral formulation of a glucagon-like peptide-1 receptor agonist, semaglutide, was developed by utilizing absorption enhancers. Nevertheless, a strict patient adherence to medication and proper drug management is required owing to a lower absorption with food, the stability and hygroscopicity of the oral formulation. To our knowledge, there are few case reports on the effects of differences in medication and drug management on therapeutic efficacy of the oral formulation of semaglutide. In this report, we present two patients who lost clinical efficacy of the drug due to different mechanisms of medication and drug management after switching from the injectable formulation to oral formulation of the drug. The patient with reliable medication and drug management maintained blood glucose levels similar to those noted treatment with the injectable formulation and lost weight. In contrast, in the poor medication and drug management patient, blood glucose levels and body weight deteriorated to those at the beginning of diabetes treatment; this was noted after 8 months of therapy with the oral formulation. Therefore, oral formulations requiring strict medication and drug management should thoroughly be monitored by pharmacists. In addition, it was also considered necessary to select an injectable drug not solely based on the method of management but also on factors such as the convenience of weekly management to ensure treatment.
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