Impact of a Weekly GLP-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

<b>Objective: </b>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. <p> </p> <p><b>Research Design and Methods</b>: 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).</p> <p> </p> <p><b>Results<a>:</a></b> <a>Mean±SD HbA<sub>1c</sub> 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 <i>P</i><0.0001)</a>. 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; <i>P</i><0.0001) at week 26 in the albiglutide+glargine group <a></a> 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; <i>P</i><0.0001) vs. lispro+glargine. Gastrointestinal adverse events were higher with albiglutide+glargine (26% vs. 13%). </p> <p> </p> <p><b>Conclusions<a>:</a></b> 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. </p>

C‐peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective

“…In particular, C-peptide is inversely related both to glucose variability and to the magnitude of glucose excursion after meals, 12 so that estimates of C-peptide might be useful in determining whether prandial insulins should be considered, or when it might possibly be withdrawn in favour of alternative approaches such as a GLP-1 RA and/or SGLT2 inhibitor. 115,116 Large, prospective randomized clinical studies are needed to evaluate whether a clear cut-off of C-peptide can be established in this regard, towards a precision medicine approach.…”