title: 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.
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 (HbA(1c)).
  
  
  RESULTS
  Of 134 patients in the intent-to-treat population (baseline mean [SD] HbA(1c),7.2% [1.0%]), 44 were exenatide-naïve (baseline HbA(1c), 7.8% [1.0%]) and 90 switched from exenatide twice daily (baseline HbA(1c), 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) HbA(1c) 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 HbA(1c) 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 HbA(1c) and weight, while patients with the benefit of prior exenatide therapy experienced an additional reduction from baseline in HbA(1c) and no additional change in weight after 2 years. ClinicalTrials.gov identifier: NCT00753896.
authors.affiliation: University of California at San Francisco, Fresno, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Norwood
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Liutkus
authors.forename: Harry
authors.initials: H
authors.lastname: Haber
authors.forename: Ella
authors.initials: E
authors.lastname: Pintilei
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Boardman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Trautmann
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077205:Pioglitazone; D018027:Receptors, Glucagon / Q000819:agonists; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D000077205:Pioglitazone; D018027:Receptors, Glucagon; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014688:Venoms; C000593833:GLP1R protein, human