GLP-1

Name

Types

Structure Features

Exenatide

Short-acting

Exenatide is a 39-amino acid peptide amide with 53% amino acid sequence identity to human GLP-1. A key amino acid substitution at position 2 confers complete resistance to DPP-4.

Liraglutide

Short-acting

With 97% amino acid residue identity, Liraglutide is structurally similar to natural GLP-1 (7-37). The differences between Liraglutide and human GLP-1 are that Lys is replaced by Arg at position 28; glutamate spacer at Lys in position 20 conjugates palmitic acid. Through binding to serum albumin and self-binding in the subcutaneous space, fatty acid conjugation prolongs the duration of action.

Albiglutide

Long-acting

Albiglutide is a tandem fusion of two GLP-1(7-36) molecules with human serum albumin. The peptide sequence is shifted from Gly to Ala at position 8, which increases resistance to DPP-4 mediated protein aggregation. In addition, fusion of this peptide with albumin prolongs its half-life in humans by 6-8 days.

Dulaglutide

Long-acting

Dulaglutide is a GLP-1 (7-37) polypeptide analog consisting of recombinant DNA covalently fused to IgG Fc. The structure of dulaglutide improves solubility, reduces immunogenicity and decreases renal clearance.

Lixisenatide

Short-acting

Lixisenatide includes a 44-amino acid peptide with a similar structure to exenatide (differing only by one amino acid). The original exenatide sequence was extended by adding six lysine residues to the C-terminus and removing proline from the C-terminus. This modification slightly extended the half-life of exenatide to 3-4 hours, allowing it to be injected subcutaneously once a day and, more importantly, quadrupling its binding to the GLP-1 receptor.

Semaglutide

Long-acting

As a long-acting GLP-1 agonist, semaglutide differs from liraglutide in two sites. Pos2 is replaced by Aib(U)-a modification that significantly protects it from enzymatic degradation by the DPP-4. In addition, the modified fatty acid chain and the two PEG2 intermediates have been shown to be optimal for prolonged efficacy both in vitro and in vivo.

Beinaglutide

Short-acting

Benalutide is a recombinant human GLP-1 polypeptide (rhGLP-1) that is almost 100% homologous to human GLP-1 (7-36).

PEG-Loxenatide

Long-acting

Polyethylene glycol loxenatide (PEG-Loxe) is a novel PEG linked GLP-1 analogs. Loxenatide is derived from exendin-4, with 53% homology to human GLP-1.

Generic name

Brand Name/

Altermative name

Expression System

Indications

Manufacturer

Latest stage

Liraglutide Recombinant

Saxenda,Victoza,诺和力

Yeast (Saccharomyces cerevisiae)

Cardiovascular diseases, Obesity, Overweight, Type 2 diabetes mellitus

Novo Nordisk

Approval

Semaglutide (Injection)

Ozempic, Wegovy,诺和泰

Yeast

Type 2 diabetes mellitus, Overweight, Obesity, Heart failure, Nonalcoholic Steatohepatitis,

Novo Nordisk

Approval

Semaglutide (Oral)

Rybelsus

Yeast

Type 2 diabetes mellitus, Overweight, Obesity, Alzheimer's disease

Novo Nordisk

Approval

Albiglutide

Albugo, Eperzan, Syncria

Yeast (Saccharomyces
cerevisiae)

Type 2 diabetes mellitus

GSK

Withdraw

Bydureon, Byetta

Exenatide

N.A. (Chemical synthesis)

Type 2 diabetes mellitus

Amylin Pharmaceutical,AstraZeneca

Approval

Dulaglutide

Trulicity

CHO cell

Type 2 diabetes mellitus

Eli Lilly

Approval

Beinaglutide

谊生泰,菲塑美

E. coli

Type 2 diabetes mellitus, Obesity , Overweight

Shanghai Benemae Pharmaceutical

Approval

Liraglutide Biosimilar

利鲁平

E. coli

Type 2 diabetes mellitus, Obesity, Overweight, Diabetes

Hangzhou Zhongmei, Jiuyuan Gene Engineering

Approval

Liraglutide Biosimilar

统博力

Pending Update

Type 2 diabetes mellitus

Tonghua Dongbao

Approval

Ecnoglutide

XW003

E. coli

Type 2 diabetes mellitus | Obesity | Nonalcoholic Steatohepatitis(nonalcoholic steatohepatitis,NASH)

Sciwind Biosciences

Phase III

Exendin-4

Recombinant exenatide, active substance

Pending Update

Type 2 diabetes mellitus

Dongguan Baolijian Bioengineering

Phase III

Recombinant exendin 4

UNI RE4

Pending Update

Type 2 diabetes mellitus

Uni-Bio Science Group

Phase III

rExenatide-4

Recombinant exenatide-4, RE-4

Pending Update

Type 2 diabetes mellitus

CSPC Zhongqi Pharmaceutical Technology

Phase III

Liraglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

SL Pharmaceutica,Protein-Way Biotechnology

Phase III

Liraglutide biosimilar

Pending Update

Pending Update

Obesity | Overweight | Type 2 diabetes mellitus

Wanbang Biopharmaceuticals

Phase III

Liraglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

Zhuhai United Laboratories

Phase III

Semaglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

Livzon Group

Phase III

Avexitide

Avexitide (USAN),Avexitide acetate,Exendin 9-39

Pending Update

Post-Bariatric Hypoglycemia (PBH), Congenital Hyperinsulinism (HI)

Cambridge University Press, Eiger BioPharmaceuticals, Stanford University

Phase II

Efinopegdutide

Glucagon, JNJ-64565111, HM12525A, MK-6024

Pending Update

Nonalcoholic Steatohepatitis | Type 2 diabetes mellitus

Hanmi Pharmaceutical, MSD

Phase II

Oxyntomodulin

Pending Update

Pending Update

Type 2 diabetes mellitus, Obesity

Xenetic Biosciences, Pharmsynthez PJSC

Phase II

PB-1023

Glymera, GLP-1-ELP-120

Pending Update

Type 2 diabetes mellitus

PhaseBio harmaceuticals, ImmunoForge

Phase II

Retatrutide

LY 3437943

Pending Update

Obesity | Overweight, Type 2 diabetes mellitus

Eli Lilly

Phase II

GZR-18

GZR18

Pending Update

Type 2 diabetes mellitus | Obesity, Overweight

Gan & Lee Pharmaceuticals

Phase I / II

E2HSA

Recombinant exenatide-human serum albumin fusion protein

Pending Update

Diabetes

Zhejiang Huayang

Phase I

GLP-1 analogue fusion protein

Recombinant human glucagon-like peptide-1 analog fusion protein, human serum albumin(HSA)

Pending Update

Diabetes

Jiangsu T-Mab Biopharma

Phase I

HB 1085

Insulinotropic Hormone Secretion Peptide Fusion Protein

Pending Update

Type 2 diabetes mellitus, Obesity

Wuxi Hebang

Phase I

Exendin-9,39

Exenatide9-39

Pending Update

Diabetes | Obesity

Mayo Clinic

Phase I

Glucagon-like peptide 1

Pending Update

Pending Update

Type 1 diabetes mellitus, Insulin Resistance

University of Virginia Foundation

Phase I

NN-9277

Pending Update

Pending Update

Overweight

Novo Nordisk A/S

Phase I

Oxyntomodulin peptide analogs

OXM, glucagon-37

Pending Update

Diabetes, Obesity

Imperial College London

Phase I

VTC-G15

Pending Update

Pending Update

Type 1 diabetes mellitus

Mass General Brigham, Inc.

Phase I

XW-004

Oral GLP-1 analog

Pending Update

Type 2 diabetes mellitus, Nonalcoholic Steatohepatitis, Obesity

Sciwind Biosciences

Phase I

XW-014

XW-014

Pending Update

Type 2 diabetes mellitus, Nonalcoholic Steatohepatitis, Obesity

Sciwind Biosciences

Phase I

Liraglutide biosimilar

TQZ2451

Pending Update

Type 2 diabetes mellitus

Chia Tai Tianqing Pharmaceutical

Submit for Approval

Liraglutide biosimilar

4P-004,4P004

Pending Update

Knee Arthritis

4Moving Biotech

Phase I

Liraglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

Sciwind Biosciences, Etinpro

Phase I

Semaglutide biosimilar &Shanghai Bovax Biotechnology)

Pending Update

Pending Update

Type 2 diabetes mellitus

Chongqing Chenan Biopharmaceutical, Shanghai Bovax Biotechnology

Phase I

Semaglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

Hangzhou Zhongmei Huadong, Chongqing Paijin Biotechnology

Phase I

Semaglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus, Alzheimer's disease, Nonalcoholic Steatohepatitis, Obesity

Zhuhai United Laboratories, Zhongshan Branch

Phase I

Semaglutide Biosimilar

PJ-007

Pending Update

Type 2 diabetes mellitus, Obesity

Huadong Medicine, Chongqing Peg-Bio Biopharma

Phase I

Liraglutide biosimilar

Pending Update

Pending Update

Type 2 diabetes mellitus

Nobot Biotechnology

Clinical Trial Application

Semaglutide biosimilar

Pending Update

Pending Update

Pending Update

Zhuhai United

Clinical TrialApplication