Online-Only Supplementary Material_RosenstockJuly2020.pdf (1.2 MB)

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

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posted on 21.09.2020 by Julio Rosenstock, Antonio Nino, Joseph Soffer, Lois Erskine, Andre Acusta, Jo Dole, Molly C. Carr, Jason Mallory, Philip Home
Objective: The principle of replacing prandial insulin lispro with a once-weekly GLP-1 receptor agonist (GLP-1RA) in 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+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 HbA1c 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, were reduced at week 26 to 6.7±0.8% (49±8 mmol/mol) and 6.6±0.8% (48±8 mmol/mol); respectively (LS difference 0.06% [95% CI, −0.05 to 0.17]; noninferiority P<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 62U/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 GLP1RA arm. Replacing prandial insulin with a weekly GLP-1RA can simplify basal+prandial insulin treatments and achieve better outcomes in type 2 diabetes.

Funding

This study (NCT02229227) was funded by GlaxoSmithKline.

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