Gut hormone analogues and skeletal health in diabetes and obesity: Evidence from preclinical models

Peptides. 2024 Jul:177:171228. doi: 10.1016/j.peptides.2024.171228. Epub 2024 Apr 23.

Abstract

Diabetes mellitus and obesity are rapidly growing worldwide. Aside from metabolic disturbances, these two disorders also affect bone with a higher prevalence of bone fractures. In the last decade, a growing body of evidence suggested that several gut hormones, including ghrelin, gastrin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, and glucagon-like peptide-1 and 2 (GLP-1 and GLP-2, respectively) may affect bone physiology. Several gut hormone analogues have been developed for the treatment of type 2 diabetes and obesity, and could represent a new alternative in the therapeutic arsenal against bone fragility. In the present review, a summary of the physiological roles of these gut hormones and their analogues is presented at the cellular level but also in several preclinical models of bone fragility disorders including type 2 diabetes mellitus, especially on bone mineral density, microarchitecture and bone material properties. The present review also summarizes the impact of GLP-1 receptor agonists approved for the treatment of type 2 diabetes mellitus and the more recent dual or triple analogue on bone physiology and strength.

Keywords: Bone; Dual analogue, Diabetes mellitus; GIP; GLP-1; GLP-2; Obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Gastric Inhibitory Polypeptide / metabolism
  • Gastric Inhibitory Polypeptide / therapeutic use
  • Gastrointestinal Hormones* / metabolism
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Obesity* / drug therapy
  • Obesity* / metabolism

Substances

  • Gastrointestinal Hormones
  • Glucagon-Like Peptide 1
  • Gastric Inhibitory Polypeptide