Anti-GCG monoclonal antibody, clone 430DU47.20.20

Background: The global incidence of type 2 diabetes (T2D) continues to increase annually, and persons with T2D typically require regular changes in pharmacologic invention for achieving glycemic targets. Healthcare providers must consider multiple factors when selecting a 2nd line. This retrospective cohort study evaluates impact of two common anti-diabetes medication classes (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) on the well-known composite 3-point major cardiovascular events outcome (3P-MACE, comprised of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). No significant impact was found. Persons with T2D face increased risks of many adverse cardiovascular outcomes. This study duplicated common inclusion and exclusion criteria to create an observational cohort from a large healthcare system's electronic health records for testing DPP-4i and GLP-1RA against each other to evaluate impact on likelihood to develop 3P-MACE. Methods: The statistical model and analyses were based on a cohort of 5,518 adult patients with T2D who were prescribed metformin and either DPP-4i or GLP-1RA to control glycemia during clinic visits between January 2005 and September 2019. A Cox proportional hazards model was developed from the cohort to predict the 3P-MACE endpoint. Results: The model did not show a meaningful difference in likelihood of developing the 3P-MACE outcome between patients treated with DPP-4i compared to patients treated with GLP-1RA. Conclusions: Prior history of cardiovascular disease (CVD) did not impact this small difference between the two classes of drug.

Objective Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been reported to have therapeutic effects on diabetes and various diseases. Precise detection of GLP-1 receptor (GLP-1R) can be useful to diagnose and elucidate the mechanism of such diseases. Here we aimed to develop an imaging probe based on GLP-1RA that has high molar activity and sensitivity for detection of low-level GLP-1R expression in non-pancreatic diseases. Methods We selected the agonist exenatide (Ex4) as the parent peptide of a GLP-1R targeting probe and prepared Cys-Ex4 by addition of an N-terminal Cys residue and labeling with the prosthetic agentN-(3-[I-125]iodophenyl)maleimide ([I-125]IPM) to generate [I-125]Ex4(ipm.)We evaluated the affinity of [I-125]Ex4(ipm)for GLP-1R, as well as cellular binding profiles in insulinoma and prostate cancer cell lines, and in vivo biodistributions in normal and tumor-bearing mice to assess GLP-1R-dependent accumulation of radioactivity in tissues. Results [I-125]Ex4(ipm)was easily synthesized with high radiochemical yield (73%), radiochemical purity (> 99%), and molar activity (81 GBq/mu mol) via a thiol/maleimide reaction. Following administration to mice, [I-125]Ex4(ipm)accumulated to high levels in the pancreas (23.3% ID/g), with radioactivity co-localizing in areas having insulin-positive beta cells. High amounts of radioactivity also accumulated in insulinomas that overexpressed GLP-1R (27.5% ID/g). In contrast, low amounts of [I-125]Ex4(ipm)accumulation, corresponding to low expression levels of GLP-1R, were observed in prostate cancer cells and xenografts used as a model of non-pancreatic applications. Conclusion Our results suggested that [I-123]Ex4(ipm)could be valuable for GLP-1R imaging in diabetes, insulinomas, and various diseases related to GLP-1R.