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Review
. 2022 Mar 1:13:838410.
doi: 10.3389/fendo.2022.838410. eCollection 2022.

Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes

Qiming Tan  1 , Seun E Akindehin  2 , Camila E Orsso  3 , Richelle C Waldner  1 , Richard D DiMarchi  4 , Timo D Müller  2 , Andrea M Haqq  1   3
Affiliations
Review

Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes

Qiming Tan et al. Front Endocrinol (Lausanne). .

Abstract

The incretin hormone glucagon-like peptide-1 (GLP-1) has received enormous attention during the past three decades as a therapeutic target for the treatment of obesity and type 2 diabetes. Continuous improvement of the pharmacokinetic profile of GLP-1R agonists, starting from native hormone with a half-life of ~2-3 min to the development of twice daily, daily and even once-weekly drugs highlight the pharmaceutical evolution of GLP-1-based medicines. In contrast to GLP-1, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) received little attention as a pharmacological target, because of conflicting observations that argue activation or inhibition of the GIP receptor (GIPR) provides beneficial effects on systemic metabolism. Interest in GIPR agonism for the treatment of obesity and diabetes was recently propelled by the clinical success of unimolecular dual-agonists targeting the receptors for GIP and GLP-1, with reported significantly improved body weight and glucose control in patients with obesity and type II diabetes. Here we review the biology and pharmacology of GLP-1 and GIP and discuss recent advances in incretin-based pharmacotherapies.

Keywords: GIP; GLP-1; diabetes; drug; incretin; obesity.

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Conflict of interest statement

AH is an investigator on clinical trials for Rhythm Pharmaceuticals, Inc., and Levo Therapeutics, has received grant funding from the W. Garfield Weston Foundation, and has served as a speaker for Rhythm Pharmaceuticals, Inc. TM receives research funding by Novo Nordisk, but these funds are unrelated the here described work. TM further received speaking fees from Eli Lilly, Novo Nordisk, Mercodia, AstraZeneca, Berlin Chemie, and Sanofi Aventis. RD is a co-inventor on intellectual property owned by Indiana University and licensed to Novo Nordisk. He was recently employed by Novo Nordisk and previously Lilly Research Laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with several of the authors SA and TM.

Figures

Figure 1
Figure 1
Complications of obesity. COPD, chronic obstructive pulmonary disease; IBD, inflammatory bowel disease; PCOS, polycystic ovary syndrome; T2D, type 2 diabetes. Images retrieved from smart.servier.com.
Figure 2
Figure 2
Biological actions of (A) GLP-1 and (B) GIP on target tissues. Direct and indirect effects are depicted. Images retrieved from smart.servier.com.
Figure 3
Figure 3
Timeline of drug approvals by the U.S. Food and Drug Administration.
Figure 4
Figure 4
Methods to enhance GLP- 1R action. DPP- 4, dipeptidylpeptidase-4; GLP- 1, glucagon-like peptide-1.
See this image and copyright information in PMC

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