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Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

ABSTRACT: AIMS/INTRODUCTION:Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy. GLP-1R-targeted imaging has recently emerged to visualize and quantify ?-cells. We investigated whether GLP-1R-targeted imaging can predict the efficacy of GLP-1RA treatment. MATERIALS AND METHODS:We developed 111 Indium-labeled exendin-4 derivative (111 In-Ex4) as a GLP-1R-targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11% fat chow. After 3-week administration of dulaglutide as GLP-1RA therapy, mice with non-fasting blood glucose levels <300 mg/dL and >300 mg/dL were defined as responders and non-responders, respectively. In addition, ex vivo 111 In-Ex4 pancreatic accumulations (111 In-Ex4 pancreatic values) were examined. RESULTS:The non-fasting blood glucose levels after treatment were 172.5 ± 42.4 mg/dL in responders (n = 4) and 330.8 ± 20.7 mg/dL in non-responders (n = 5), respectively. Ex vivo 111 In-Ex4 pancreatic values showed significant correlations with post-treatment glycohemoglobin and glucose area under curve during an oral glucose tolerance test (R2 = 0.76 and 0.80; P < 0.01 and <0.01, respectively). The receiver operating characteristic area under curve for identifying responders by ex vivo 111 In-Ex4 pancreatic values was 1.00 (P < 0.01). CONCLUSION:Ex vivo 111 In-Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP-1R-targeted imaging applications.

SUBMITTER: Murakami T

PROVIDER: S-EPMC7610126 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

Murakami Takaaki T Fujimoto Hiroyuki H Fujita Naotaka N Hamamatsu Keita K Yabe Daisuke D Inagaki Nobuya N

Journal of diabetes investigation 20200601 6

<h4>Aims/introduction</h4>Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy. GLP-1R-targeted imaging has recently emerged to visualize and quantify β-cells. We investigated whether GLP-1R-targeted ...[more]

PMID: 32323451

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Project description:BACKGROUND:Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS:MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. RESULTS:Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%; sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%) than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. CONCLUSION:Dulaglutide is effective in the treatment of patients with type 2 diabetes but we need long follow-up data for safety concerns.

Dataset Information

Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

Publications

Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

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