Impact Of A Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, On Glycemic Control And On Reducing Prandial Insulin Use In Type 2 Diabetes Inadequately Controlled On Multiple Insulin Therapy: A Randomized Trial

OBJECTIVE The principle of replacing prandial insulin lispro with a once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) for type 2 diabetes inadequately controlled on a multiple daily insulin injections regimen was tested with albiglutide. RESEARCH DESIGN AND METHODS In this treat-to-target study, basal plus prandial insulin was optimized over 4 weeks before participants were randomized (1:1) to albiglutide plus optimized basal insulin glargine and lispro (dose reduced by 50% at randomization; subsequently, lispro injections were fully discontinued 4 weeks later) (n= 402) or to continued optimized lispro plus optimized glargine (n= 412). RESULTS Mean +/- SD HbA(1c)at baseline, 7.8 +/- 0.6% (61 +/- 7 mmol/mol) in the albiglutide + glargine group and 7.7 +/- 0.6% (60 +/- 7 mmol/mol) in the lispro + glargine group, was reduced at week 26 to 6.7 +/- 0.8% (49 +/- 8 mmol/mol) and 6.6 +/- 0.8% (48 +/- 8 mmol/mol), respectively (least squares [LS] difference 0.06% [95% CI -0.05 to 0.17]; noninferiorityP< 0.0001). In the albiglutide + glargine group, 218 participants (54%) replaced all prandial insulin without reintroducing lispro up to week 26. Total daily prandial insulin dose was similar at baseline but was lower by 62 units/day (95% CI -65.9 to -57.8;P< 0.0001) at week 26 in the albiglutide + glargine group, and the total number of weekly injections was also reduced from 29 to 13 per week. Less severe/documented symptomatic hypoglycemia (57.2% vs. 75.0%) occurred in the albiglutide + glargine group with meaningful weight differences (LS mean +/- SE -2.0 +/- 0.2 vs. +2.4 +/- 0.2 kg;P< 0.0001) vs. lispro + glargine. Gastrointestinal adverse events were higher with albiglutide + glargine (26% vs. 13%). CONCLUSIONS A once-weekly GLP-1RA was able to substitute for prandial insulin in 54% of people, substantially reducing the number of prandial insulin injections; glycemic control improved, with the added benefits of weight loss and less hypoglycemia in the GLP-1RA arm. Replacing prandial insulin with a weekly GLP-1RA can simplify basal plus prandial insulin treatments and achieve better outcomes in type 2 diabetes.