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

Abstract

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 5 402) or to continued optimized lispro plus optimized glargine (n 5 412). RESULTS Mean 6 SD HbA 1c at baseline, 7.8 6 0.6% (61 6 7 mmol/mol) in the albiglutide 1 glargine group and 7.7 6 0.6% (60 6 7 mmol/mol) in the lispro 1 glargine group, was reduced at week 26 to 6.7 6 0.8% (49 6 8 mmol/mol) and 6.6 6 0.8% (48 6 8 mmol/mol), respectively (least squares [LS] difference 0.06% [95% CI 20.05 to 0.17]; noninferiority P < 0.0001). In the albiglutide 1 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 265.9 to 257.8; P < 0.0001) at week 26 in the albiglutide 1 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 1 glargine group with meaningful weight differences (LS mean 6 SE 22.0 6 0.2 vs. 12.4 6 0.2 kg; P < 0.0001) vs. lispro 1 glargine. Gastrointestinal adverse events were higher with albiglutide 1 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.

Feasibility of Simplification From a Basal-Bolus Insulin Regimen to a Fixed-Ratio Formulation of Basal Insulin Plus a GLP-1RA or to Basal Insulin Plus an SGLT2 Inhibitor: BEYOND, a Randomized, Pragmatic Trial

“…Although this may be considered not optimal in term of target achievement, nonetheless, it represents the result of a simple therapeutic algorithm to be used in clinical practice both in outpatient or inpatient departments, beyond the complexity of somewhat discouraging titration protocols. In one recent randomized trial ( 21 ), the once-weekly GLP-1RA albiglutide was able to be substituted for prandial insulin in about one-half of people with type 2 diabetes inadequately controlled with a multiple daily insulin injections regimen. However, the change needed a somewhat complex protocol lasting 8 weeks, including starting with halving of the regular insulin dose, discontinuation of regular insulin at 4 weeks, and eventual reintroduction of regular insulin at 8 weeks in case of inefficacy of treatment.…”

“…Besides their practical utilization in the real life of type 2 diabetes, these studies ( 21 and the current study) represent a step toward simplification of complex insulin regimen by substituting all prandial insulin with a daily or weekly GLP-1RA. Of note, the DUAL VII randomized controlled trial has demonstrated that, in patients with uncontrolled type 2 diabetes on basal insulin and metformin, the fixed-combo IDegLira produced HbA 1c reductions comparable to BBI therapy, with lower hypoglycemia rates and weight loss ( 22 ).…”

Therapie des Typ-2-Diabetes

“…In einer kürzlich erschienenen Publikation berichteten die Autoren, dass Albiglutid bei Patienten mit Typ-2-Diabetes unter einer Basis-Bolus-Insulintherapie in 54 % der Studienteilnehmer Albiglutid prandiales Insulin vollständig ersetzen konnte mit gleichzeitiger Verbesserung der Stoffwechseleinstellung, Reduktion von Hypoglykämien und des Körpergewichts [184].…”

Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes

“…Recent advancements focus on development of GLP-1 agonists which needs less frequent dosing (once weekly) to improve patient adherence and to reduce the treatment burden [13]. Only three GLP-1 agonists-exenatide extended release, semaglutide and dulaglutide (as albiglutide is withdrawn in 2018) are currently approved for once-weekly dosing [14]. Both the subcutaneous as well as oral dosage form of semaglutide have been shown to achieve significant cardiovascular improvements in clinical studies.…”