We report our discovery of a novel series of potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from a lead identified by scaffold-hopping approach, our discovery and development efforts were focused on exploring structure−activity relationships, optimizing pharmacokinetic profile, improving in vitro and in vivo efficacy, and evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial.
Background: In light of clinical trials comparing different doses of tirzepatide with selective glucagon-like peptide-1 receptor agonist (GLP1-RA) or insulin analogue, a bayesian network meta-analysis was conducted to investigate the efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus (T2DM).Methods: We systematically searched PubMed, Embase, Web of science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to 2 May 2022. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 15.1 software. Each outcome was presented as a mean difference or an odds ratio, and the surface under the cumulative ranking curve value (SCURA).Results: Ultimately, eight eligible RCTs involving 7245 patients were included. Generally speaking, compared with basal insulin (glargine or degludec); selective GLP1-RA (dulaglutide or semaglutide once weekly), 10 and 15 mg of tirzepatide exhibited better antidiabetic and weight-loss effect, especially, 15 mg of tirzepatide was dominant on reducing glycated hemoglobin (SCURA probability: 93.5%), body weight (99.7%), and fasting serum glucose (86.6%). As for safety, insulin caused less gastrointestinal events (93.5%), and there was no statistical difference between GLP1-RA and tirzepatide.Conclusion: Compare with insulin and GLP1-RA, tirzepatide display favorable efficacy and acceptable safety for T2DM patients. More well-designed RCTs are needed to evaluate its clinical performance with higher doses of GLP1-RA and determine its potential cardiovascular benefits.
Introduction: The coronavirus disease 2019 (COVID-19) pandemic has spread globally since it outbroke in December 2019. The urgent pandemic presents an unprecedented challenge to develop and identify effective medication therapy strategies to combat the COVID-19. Areas covered: Here, we summarized and evaluated the current treatment drugs and regimens, and put forward the treatment recommendations, including using the potential repurposed or experimental drugs against COVID-19, e.g. chloroquine (CQ), hydroxychloroquine (HCQ), lopinavir/ritonavir (LPV/r), remdesivir (RDV), and favipiravir (FPV). We also analyzed the specific drugs and vaccines against SARS-CoV-2 ongoing development and formulated the comprehensive treatment regimens based on condition of patients, diseases and drugs as well as concomitant medications. Expert opinion: No drugs and vaccines have been proven to be particularly effective against SARS-CoV-2 up to now. The recommended comprehensive medication therapy strategies have already displayed favorable effect in the fight against COVID-19. Research should be focused on the development of anti-SARS-CoV-2 drugs and vaccines based on high-quality clinical trial evidence, treatment guidelines and expert consensus.
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