• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials
• Hyperglycemia/Hypoglycemia

• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials
• Hyperglycemia/Hypoglycemia
• Endocrinology
• Diabetes & Metabolic Syndrome

Jaret Malloy, PhD, Bristol-Myers Squibb, San Diego, California, USA, reported on the 3-year results of the Efficacy of Exenatide Once-Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea [DURATION-3; NCT00641056] open-label, randomized, controlled trial. Sustained HbA1C, greater weight reduction, and less frequent hypoglycemia were evident up to 3 years in subjects with type 2 diabetes mellitus (T2DM) compared with insulin glargine [Malloy J et al. EASD 2013 (abstr 2)].

Sustained control of glucose levels becomes increasingly difficult in T2DM because of the temporally progressive decline in insulin secretion. Typically, more intensive therapy is needed. The present study compared the abilities of the glucagon-like peptide-1 receptor agonist exenatide and insulin glargine to sustain HbA1C control, defined as achieving and maintaining HbA1C ≤7% (53 mmol/L) after 26 weeks of treatment. Loss of HbA1C control, or failure to achieve control, was evident as HbA1C >7% at two consecutive visits 10 to 12 weeks apart or HbA1C >9% at a single visit after 26 weeks of treatment. Insulin glargine dose was established using the Initiate Insulin by Aggressive Titration and Education (INITIATE) algorithm.

Patients in the intention-to-treat (ITT) group (n=466) who received exenatide (n=233) or insulin glargine (n=223) were followed through a 26-week core phase with an option for continued treatment for up to 156 weeks. At baseline, the exenatide and insulin glargine arms were similar in mean age (57 and 58 years), proportion of males (52% and 55%), mean duration of diabetes (both ∼8 years), and mean HbA1C (both 8.3%). Metformin alone and metformin along with a sulfonylurea was taken by 70% and 30% of patients, respectively, in both study arms. Of the ITT group, 140 exenatide patients and 147 insulin glargine patients continued treatment for the full 3 years.

HbA1C control was achieved and sustained at the last visit by 50% of exenatide patients and 43% of insulin glargine patients in the ITT population. Of the patients treated with exenatide and insulin glargine for 3 years, the rate of HbA1C control was 43% and 33%, respectively. HbA1C control was maintained longer for those receiving exenatide (median 25.0 months) than for insulin glargine patients (median 16.7 months). Of those who displayed HbA1C control until the last visit, a more pronounced reduction of the level of HbA1C was evident in patients receiving exenatide (least squares [LS] mean −1.32%) than in insulin glargine patients (LS mean −1.17%; 95% CI difference, −0.34 to 0.04; p=0.12). Exenatide patients displayed less reduction in fasting serum glucose and greater weight loss (LS mean −2.28 mmol/L and −3.44 kg, respectively) than insulin glargine patients (LS mean −3.07; 95% CI difference, 0.03 to 1.54; p=0.04; and LS mean +0.70 kg; 95% CI difference, 5.71 to −2.56; p<0.0001, respectively). Exenatide patients displayed less hypoglycemia than insulin glargine patients (event rate per year 1.1 vs 3.1), but the rates of nausea (16% and 2%) and diarrhea (14% and 7%) were more common in exenatide patients than insulin glargine patients.

Despite continued uptitration of insulin, patients with T2DM treated with exenatide displayed better HbA1C control, greater weight reduction, and less frequent hypoglycemia than patients treated with insulin glargine.

• © 2013 MD Conference Express®