Glucagon-like peptide-1 receptor agonists (GLP-1RA) are powerful second-line agents for the treatment of type 2 diabetes. GLP-1RA have bene marketed in 2010 in Italy and years of experience have accumulated for the treatment with this class of drugs. Cardiovascular outcome trials have shown that type 2 diabetic patients with established cardiovascular disease treated with GLP-1RA have a lower risk of future cardiovascular events.
In this real world study, we wish to evaluate retrospectively the effectiveness and persistence on treatment of GLP-1RA therapy in patients with type 2 diabetes from 2010 to 2018.
Effectiveness endpoints will be glycemic (fasting plasma glucose and HbA1c) and extra-glycemic (body weight and blood pressure). Data from diabetes outpatient clinics in North East Italy will be automatically extracted from electronic chart records and collected into a unique database.
Different groups of GLP-1RA therapies will be compared:
Long-acting (e.g. dulaglutide and exenatide once weekly) versus short acting (exenatide, liraglutide and lixisenatide)
Fixed versus flexible combinations of GLP-1RA and basal insulin.
GLP-1RA with similarities to human GLP-1 (e.g. liraglutide) versus exendin-based GLP-1RA (e.g. exenatide).

Start Date19 Dec 2018

Sponsor / Collaborator

University of Padua

100 Clinical Results associated with Recombinant glucagon-like peptide-1 receptor agonist(Chengdu Zhitian Biological Engineering Co Ltd)

100 Translational Medicine associated with Recombinant glucagon-like peptide-1 receptor agonist(Chengdu Zhitian Biological Engineering Co Ltd)

100 Patents (Medical) associated with Recombinant glucagon-like peptide-1 receptor agonist(Chengdu Zhitian Biological Engineering Co Ltd)

Literatures (Medical) associated with Recombinant glucagon-like peptide-1 receptor agonist(Chengdu Zhitian Biological Engineering Co Ltd)

10 Jan 2019·Circulation reports

Anti-Diabetic Agents and Heart Failure　― Response to the CARMELINA Study ―

Review

Author: Sano, Motoaki

According to cardiovascular outcome trials, some anti-diabetic drugs can improve cardiovascular outcomes in patients with type 2 diabetes. Sodium glucose cotransporter 2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) have a strong preventive effect on both hospitalization for heart failure and the decline in kidney function in patients with type 2 diabetes, while glucagon-like peptide-1 receptor agonists, especially human glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and albiglutide), suppress arteriosclerotic diseases (stroke and myocardial infarction). Using these medications in combination could possibly prevent both hospitalization for heart failure and arteriosclerotic events. Dipeptidyl peptidase 4 (DPP-4) inhibitors are preferentially used as add-on therapy for type 2 diabetes. Cardiovascular outcome trials conducted so far suggest that DPP-4 inhibitors (sitagliptin, alogliptin, and saxagliptin) do not promote arteriosclerotic disease, but there may be a difference between these drugs with regard to safety for heart failure. Previous cardiovascular outcome trials have mainly focused on type 2 diabetes patients with established cardiovascular disease. In contrast, the CARMELINA study investigated the cardiovascular safety of linagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes and kidney dysfunction.

01 Dec 2017·Clinical drug investigationQ4 · MEDICINE

Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus

Q4 · MEDICINE

Article

Author: Chen, Yingli ; Zhao, Xia ; Fang, Yi ; Cui, Yimin ; Zhu, Lixia ; Guo, Xiaohui ; Wang, Yitong ; Ji, Linong ; Wang, Qian ; Xu, Bingfeng ; Xu, Ling ; Lou, Kun

BACKGROUND AND OBJECTIVES:

Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM).

DESIGN AND METHODS:

In the randomized, open-label study, Chinese patients with T2DM (n = 36) were randomly assigned to three groups of rE-4 (n = 12), rE-4 with metformin (n = 12) and exenatide (n = 12, as the control group) for 12 weeks. rE-4 and exenatide were administered by subcutaneous injection in the abdomen, and metformin was given by oral administration. Patients received rE-4 or exenatide 5 μg twice a day for the first 4 weeks and adjusted the dose of rE-4 or exenatide to 10 μg twice a day at day 29 for the following 8 weeks, if their glycated albumin (GA) values were still greater than 17%. We evaluated pharmacokinetic parameters of rE-4 and exenatide, fasting plasma glucose (FPG), 2-h postprandial blood glucose (PG2 h), glycosylated hemoglobin (HbA1c) and body weight at designated time points.

RESULTS:

Thirty-six patients were enrolled, and 29 subjects finished the study. rE-4 was absorbed quickly with a median peak-reaching time (t _max) of 0.8-1.5 h and eliminated rapidly with a median terminal half-life (t _1/2z) of 1.6-1.9 h. The exposure of rE-4 increased in an approximately dose-proportional method without accumulation. rE-4 10 μg twice a day could reduce FPG (~2.29 mmol/L), PG2 h (~6.00 mmol/L), HbA1c (~1.19%) and body weight (~0.48 kg) from baseline to 12 weeks, with no statistical significance compared with exenatide (FPG: ~1.88 mmol/L; PG2 h: ~6.66 mmol/L; HbA1c: ~1.13%; body weight: ~0.47 kg) and rE-4 with metformin (FPG: ~2.33 mmol/L; PG2 h: ~6.51 mmol/L; HbA1c: ~0.84%; body weight: ~1.16 kg) (p > 0.05).

CONCLUSIONS:

rE-4 twice a day has a pharmacokinetic profile similar to exenatide and rE-4 with metformin after single and multiple doses in Chinese patients with T2DM. Also, rE-4 could improve glycemic control effectively. CLINICALTRIALS.

GOV IDENTIFIER:

NCT01342042.

01 Aug 2017·International journal of clinical pharmacology and therapeuticsQ4 · MEDICINE

Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2 diabetes mellitus

Q4 · MEDICINE

Article

Author: Zheng, Qing-Shan ; Zhang, Min-Jie ; Wang, Chen ; Fang, Yi ; Ji, Li-Nong ; Wang, Qian ; Wang, Yi-Tong ; Guo, Wei ; Zang, Yan-Nan

OBJECTIVE:

To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment.

METHODS:

Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%. The population pharmacokinetic model was developed in the nonlinear mixed-effects modeling software NONMEM.

RESULTS:

The data were best described by a two-compartment model with first-order absorption and elimination. The outcome parameters were as follows: apparent clearance (CL/F) 6.67 L/h, apparent distribution volume of central compartment (V_c/F) 19.4 L, absorption rate constant (K_a) 1.39 h^-1, apparent distribution volume of peripheral compartment (V_p/F) 22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual variabilities for CL/F, V_c/F, K_a, and Q/F were 64.4%, 57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of proportional error model was 41.7%. No covariate was screened out that showed significant influence on the model parameters.

CONCLUSIONS:

The established two-compartment model with first-order absorption and elimination successfully described the pharmacokinetic characteristics of rE-4 in Chinese patients with T2DM. .

100 Deals associated with Recombinant glucagon-like peptide-1 receptor agonist(Chengdu Zhitian Biological Engineering Co Ltd)

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 1	CN	Chengdu Zhitian Bioengineering Co., Ltd.	-

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