Exenatide extended release in patients with type 1 diabetes with and without residual insulin production

Abstract

Aims: To test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function. Methods: We performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug. Results: At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production.

Breaking and restoring immune tolerance to pancreatic beta-cells in type 1 diabetes

“…In clinical trials with albiglutide [65] and rapamycin and vildagliptin [66], restoration of the betacell function was not observed. However, using vildagliptin, liraglutide or exenatide, the exogenous insulin requirement of patients was reduced [66][67][68].…”

New advances in type 1 diabetes

“…4950 Liraglutide 1.8 mg in people with type 1 diabetes and higher body mass index decreased HbA 1c , weight, and insulin requirements with no increased hypoglycemia risk 94. However, on the basis of results from a study of weekly exenatide that showed similar results, these effects may not be sustained 51. A meta-analysis of 24 studies including 3377 participants showed that the average HbA 1c decrease from GLP-1 receptor agonists compared with placebo was highest for liraglutide 1.8 mg daily (−0.28%, 95% confidence interval −0.38% to−0.19%) and exenatide (−0.17%, −0.28% to 0.02%).…”

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics

“…Glucagon-like peptide-1 receptor (GLP-1R) agonists as adjunctive therapies have been tested in T1D patients (6), and some individuals who are overweight or have detectable levels of C-peptide might benefit from those medications (6). GLP-1R agonists also exert protective effects on bone tissue in vitro and in vivo (7)(8)(9). Some clinical studies have found neutral effects of liragutide on bone, but there was also a few meta-analysis of 16-59 randomized controlled trials with 11,206-49,602 patients with T2DM which showed that compared with placebo and other antidiabetic drugs, liraglutide was associated with a significant reduction in the risk of bone fractures (10)(11)(12)(13).…”