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Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION‐7 randomized study
Author(s) -
Guja Cristian,
Frías Juan P.,
Somogyi Aniko,
Jabbour Serge,
Wang Hui,
Hardy Elise,
Rosenstock Julio
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13266
Subject(s) - exenatide , medicine , placebo , postprandial , type 2 diabetes , metformin , insulin glargine , gastroenterology , endocrinology , insulin , clinical endpoint , diabetes mellitus , urology , randomized controlled trial , alternative medicine , pathology
Aims To compare the efficacy and safety of adding the glucagon‐like peptide‐1 receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with type 2 diabetes who were inadequately controlled despite titrated insulin glargine (IG) ± metformin. Methods This multicentre, double‐blind study ( ClinicalTrials.gov identifier: NCT02229383) randomized (1:1) patients with persistent hyperglycaemia after an 8‐week titration phase (glycated haemoglobin [HbA1c] 7.0%‐10.5% [53‐91 mmol/mol]) to exenatide QW or placebo. The primary endpoint was HbA1c change from baseline to week 28. Secondary endpoints included body weight, 2‐hour postprandial glucose, and mean daily IG dose. Results Of 464 randomized patients (mean: age, 58 years; HbA1c, 8.5% [69 mmol/mol]; diabetes duration, 11.3 years), 91% completed 28 weeks. Exenatide QW + IG vs placebo + IG significantly reduced HbA1c (least‐squares mean difference, −0.73% [−8.0 mmol/mol]; 95% confidence interval, −0.93%, −0.53% [−10.2, −5.8 mmol/mol]; P < .001; final HbA1c, 7.55% [59 mmol/mol] and 8.24% [67 mmol/mol], respectively); body weight (−1.50 kg; −2.17, −0.84; P < .001); and 2‐hour postprandial glucose (−1.52 mmol/L [−27.5 mg/dL]; −2.15, −0.90 [−38.7, −16.2]; P < .001). Significantly more exenatide QW + IG‐treated patients vs placebo + IG‐treated patients reached HbA1c <7.0% (<53 mmol/mol) (32.5% vs 7.4%; P < .001); daily IG dose increased by 2 and 4 units, respectively. Gastrointestinal and injection‐site adverse events were more frequent with exenatide QW + IG (15.1% and 7.8%, respectively) than with placebo + IG (10.8% and 3.0%, respectively); hypoglycaemia incidence was similar between the exenatide QW + IG (29.7%) and placebo + IG (29.0%) groups, with no major hypoglycaemic events. Conclusions Among patients with inadequate glycaemic control, exenatide QW significantly improved glucose control and decreased body weight, without increased hypoglycaemia or unexpected safety findings.