Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With a Thiazolidinedione Alone or in Combination With Metformin for 2 Years

• Published in: Clinical therapeutics 2012-10, Vol.34 (10), p.2082-2090
• Main Authors: Norwood, Paul, MD, FACP, Liutkus, Joanne F., MSW, MD, FRCP, Haber, Harry, MPH, Pintilei, Ella, MD, Boardman, Marilyn K., PharmD, Trautmann, Michael E., MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Clinical trials; Consciousness; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; exenatide; Female; GLP-1 receptor agonist; Glucagon-Like Peptide-1 Receptor; Glucose; glucose control; Glycated Hemoglobin A - metabolism; HbA1c; Heart attacks; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Internal Medicine; Male; Medical Education; Medical sciences; metformin; Metformin - administration & dosage; Metformin - adverse effects; Metformin - therapeutic use; Middle Aged; Peptides - administration & dosage; Peptides - adverse effects; Peptides - therapeutic use; Pharmacology. Drug treatments; Receptors, Glucagon - agonists; Statistical methods; Thiazolidinediones - administration & dosage; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use; type 2 diabetes mellitus; TZD; Venoms - administration & dosage; Venoms - adverse effects; Venoms - therapeutic use
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2012.09.007

Abstract Background Patients with type 2 diabetes mellitus are routinely treated with combinations of glucose-lowering agents. The adverse event (AE) profile and effects on glycemic control have not been assessed for the glucagon-like peptide-1 receptor agonist exenatide once weekly in combination with a thiazolidinedione (TZD) with or without metformin. Objective This study was conducted to examine the long-term safety profile and changes in glycemic control and weight for exenatide once weekly with TZD with or without metformin in patients with type 2 diabetes mellitus over 2 years. Methods In this single-arm, open-label trial with treatment up to 104 or 117 weeks, patients received 2 mg exenatide once weekly while continuing treatment with a TZD with or without metformin. Patients were either exenatide-naïve before this study or had previously received exenatide twice daily, which was discontinued on initiating exenatide once weekly. Patients were on a stable dosage of TZD (rosiglitazone or pioglitazone) and, if applicable, metformin. Treatment-emergent AEs were defined as those first occurring or worsening post baseline. Descriptive statistics were used for absolute and change-from-baseline data, and a one-sample t test for within-group change in glycosylated hemoglobin (HbA1c ). Results Of 134 patients in the intent-to-treat population (baseline mean [SD] HbA1c ,7.2% [1.0%]), 44 were exenatide-naïve (baseline HbA1c , 7.8% [1.0%]) and 90 switched from exenatide twice daily (baseline HbA1c , 7.0% [0.8%]). Of intent-to-treat patients, 106 (79%) completed the final treatment visit (week 104 or week 117). The most common AEs were nausea (17% of patients) and injection-site nodule (12% of patients). Serious AEs were reported in 14% of patients and 5% withdrew because of a treatment-emergent AE. No identifiable pattern of serious AEs was observed. There were 4 reports of edema and no reports of heart failure. No major hypoglycemia was reported; minor hypoglycemia was reported in 4% of patients. Exenatide-naïve patients experienced mean (SE) HbA1c reductions of −0.7% (0.2%) and weight reductions of −2.7 (0.8) kg, whereas patients with prior exposure to exenatide twice daily experienced a reduction of −0.4% (0.1%) in HbA1c and no change in weight. Conclusions Adverse events over 2 years were consistent with the reported safety profiles of exenatide once weekly and TZDs. Exenatide-naïve patients experienced improvements in HbA1c and weight, while patients with