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

• Published in: Diabetes care Vol. 43; no. 10; pp. 2509 - 2518
• Main Authors: Rosenstock, Julio, Nino, Antonio, Soffer, Joseph, Erskine, Lois, Acusta, Andre, Dole, Jo, Carr, Molly C, Mallory, Jason, Home, Philip
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-10-2020
• Subjects: Adult; Aged; Agonists; Blood Glucose - drug effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Emerging Therapies: Drugs and Regimens; Female; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - adverse effects; Glucagon-Like Peptide 1 - analogs & derivatives; Glycated Hemoglobin A - analysis; Glycemic Control - methods; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Insulin; Insulin - administration & dosage; Insulin - adverse effects; Insulin Glargine - administration & dosage; Insulin Lispro - administration & dosage; Male; Meals; Middle Aged; Peptides; Randomization; Receptors; Research design; Treatment Failure; Weight loss; Young Adult
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc19-2316

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.
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) (
= 402) or to continued optimized lispro plus optimized glargine (
= 412).
Mean ± SD HbA
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]; noninferiority
< 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;
< 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;
< 0.0001) vs. lispro + glargine. Gastrointestinal adverse events were higher with albiglutide + glargine (26% vs. 13%).
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.