Evidence mapPaperPMID 35698011Full record

ArticlePharmaceutical research2022

Design and Development of a New Glucagon-Like Peptide-1 Receptor Agonist to Obtain High Oral Bioavailability.

Hao Chen, Yun Lu, Shuai Shi, Qiang Zhang, Xiaoli Cao, Lei Sun, Dong An, Xiaojie Zhang, Xianglin Kong, Jianping Liu

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Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Hao ChenSchool of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
Yun LuJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Shuai ShiJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Qiang ZhangJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Xiaoli CaoJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Lei SunJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Dong AnJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Xiaojie ZhangJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Xianglin KongJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China.
Jianping LiuSchool of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. jianpingliu1293@163.com.ORCID http://orcid.org/0000-0003-1825-7122
Jiangsu Hengrui Medicine (China) · CNChina Pharmaceutical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeSemaglutide is the only oral GLP-1 RA in the market, but oral bioavailability is generally limited in range of 0.4-1%. In this study, a new GLP-1RA named SHR-2042 was developed to gain higher oral bioavailability than semaglutide.

methodSelf-association of SHR-2042, semaglutide and liraglutide were assessed using SEC-MALS. The intestinal perfusion test in SD rats was used to select permeation enhancers (PEs) including SNAC, C10 and LCC. ITC, CD and DLS were used to explore the interaction between SHR-2042 and SNAC. Gastric administrated test in SD rats was used to screen SHR-2042 granules with different SHR-2042/SNAC ratios. The oral bioavailability of SHR-2042 was studied in rats and monkeys.

resultThe designed GLP-1RA, SHR-2042, gives a better solubility and lipophilicity than semaglutide. While it forms a similar oligomer with that of semaglutide. During the selection of PEs, SNAC shows better exposure than the other competing PEs including C10 and LCC. SHR-2042 and SNAC bind quickly and exhibit hydrophobic interaction. SNAC could promote monomerization of SHR-2042 and form micelles to trap the monomerized SHR-2042. The oral bioavailability of SHR-2042 paired with SNAC is 0.041% (1:0, w/w), 0.083% (1:10, w/w), 0.32% (1:30, w/w) and 2.83% (1:60, w/w) in rats. And the oral bioavailability of SHR-2042 matched with SNAC is 3.39% (1:30, w/w) in monkeys, which is over 10 times higher than that of semaglutide.

conclusionWe believe that the design and development of oral SHR-2042 will provide a new way to design more and more GLP-1RAs with high oral bioavailability in the future.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsAnimalsBiological AvailabilityGlucagon-Like Peptide 1Hypoglycemic AgentsRatsRats, Inbred SHRRats, Sprague-DawleyGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsGLP-1RAMonkeysOligomerOral bioavailabilityRats

Identifiers

PMID35698011
OpenAlexW4282834560

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.