Glucose Regulation Research Peptides

15 research peptides demonstrate glucose regulation properties. This collection covers their mechanisms, evidence base, and research applications.

FDA Approved | Metabolic / GLP-1 Agonist

Semaglutide is an FDA-approved GLP-1 receptor agonist (MW ~4113.6 g/mol, molecular formula C187H291N45O59) with 94% sequence homology to human GLP-1.

Mechanism: Semaglutide mimics the GLP-1 hormone by binding to GLP-1 receptors on pancreatic beta cells (glucose-dependent), brain (hypothalamus appetite centers), stomach, and intestines.

FDA Approved | Metabolic / Dual GIP-GLP-1 Agonist

Tirzepatide is a first-in-class dual GIP and GLP-1 receptor agonist developed by Eli Lilly, FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound) including severe obstructive sleep apnea in adults with obesity.

Mechanism: Tirzepatide (MW ~4813 g/mol, C225H348N48O68) simultaneously activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors.

Preclinical | Metabolic / Mitochondrial

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 12S rRNA gene (MT-RNR1). Discovered in 2015 by Lee et al.

Mechanism: MOTS-c activates AMPK by inhibiting the folate cycle, causing accumulation of AICAR (an AMP analog). Activated AMPK shifts cells into energy-efficient mode: enhancing glucose uptake, fatty-acid...

Phase III / NDA Filed | Metabolic / Triple Agonist

Retatrutide is a first-in-class investigational triple hormone receptor agonist (GIP, GLP-1, and glucagon) developed by Eli Lilly. In the Phase 2 trial (Jastreboff et al., NEJM 2023, n=338), the 12 mg dose achieved 24.

Mechanism: Retatrutide simultaneously activates three receptors: GLP-1 (reduces appetite, slows gastric emptying, improves insulin secretion), GIP (enhances insulin sensitivity, glucose control), and glucagon...

FDA Approved | Metabolic / GLP-1 Agonist

Liraglutide is an FDA-approved GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1. Developed by Novo Nordisk, it is approved as Victoza for type 2 diabetes and Saxenda for chronic weight management.

Mechanism: Liraglutide binds to GLP-1 receptors on pancreatic β-cells, increasing intracellular cAMP and triggering glucose-dependent insulin secretion.

Phase III / NDA Filed | Metabolic / Dual Agonist

Survodutide is an investigational dual glucagon/GLP-1 receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. Unlike tirzepatide (GIP/GLP-1), survodutide combines glucagon and GLP-1 agonism, adding glucagon-driven hepatic fat...

Mechanism: Survodutide simultaneously activates glucagon receptors (increasing hepatic fat oxidation, energy expenditure, and thermogenesis) and GLP-1 receptors (reducing appetite, slowing gastric emptying,...

Preclinical / Early Research | Cardiovascular / Vasoactive

Apelin is an endogenous peptide ligand for the APJ receptor (APLNR), existing in multiple bioactive forms including apelin-13, apelin-17, and apelin-36 derived from a 77-amino-acid preproapelin precursor.

Mechanism: Apelin binds to the APJ receptor (APLNR), a Gi-coupled GPCR. In the cardiovascular system, apelin/APJ signaling produces positive inotropy via phospholipase C activation and increased intracellular...

FDA Approved | Endocrine / Somatostatin Analog

Octreotide is a synthetic 8-amino-acid cyclic peptide (MW ~1019.2 g/mol) that mimics the pharmacological actions of natural somatostatin but with a significantly longer half-life.

Mechanism: Octreotide binds preferentially to somatostatin receptor subtypes 2 (SSTR2) and 5 (SSTR5), with moderate affinity for SSTR3.

FDA Approved | Endocrine / Somatostatin Analog

Lanreotide is a synthetic 8-amino-acid cyclic somatostatin analog (MW ~1096.3 g/mol) available as a long-acting deep subcutaneous depot injection (Somatuline Depot/Autogel).

Mechanism: Lanreotide binds with high affinity to somatostatin receptor subtypes SSTR2 and SSTR5, and with moderate affinity to SSTR3.

FDA Approved | Endocrine / Somatostatin Analog

Pasireotide is a synthetic cyclohexapeptide somatostatin analog (MW ~1164.7 g/mol) with a unique broad somatostatin receptor binding profile, exhibiting high affinity for SSTR1, SSTR2, SSTR3, and SSTR5 (40-fold higher SSTR5 affinity than octreotide).

Mechanism: Pasireotide binds to somatostatin receptor subtypes 1, 2, 3, and 5, with particularly high affinity for SSTR5.

Well-Characterized Endogenous Hormone | Endocrine / Somatostatin Analog

Somatostatin (SST-14) is an endogenous 14-amino-acid cyclic peptide hormone (MW ~1637.9 g/mol) produced in the hypothalamus, pancreatic delta cells, and gastrointestinal tract.

Mechanism: Somatostatin binds to all five somatostatin receptor subtypes (SSTR1-5), which are G-protein-coupled receptors that inhibit adenylyl cyclase.

FDA Approved | Metabolic / Pancreatic Hormone

Glucagon is a 29-amino-acid peptide hormone (MW ~3482.8 g/mol) produced by pancreatic alpha cells that serves as the primary counter-regulatory hormone to insulin.

Mechanism: Glucagon binds to the glucagon receptor (GCGR), a G-protein-coupled receptor primarily expressed in the liver, activating adenylyl cyclase and increasing intracellular cAMP.

Early Human or Mixed Evidence | Metabolic / Exercise Mimetic

AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) is a cell-permeable nucleoside analog (MW ~258.2 g/mol) that is phosphorylated intracellularly to ZMP, which directly activates AMP-activated protein kinase (AMPK).

Mechanism: AICAR enters cells via adenosine transporters and is phosphorylated by adenosine kinase to ZMP (AICA ribotide), an AMP analog.

Animal/Preclinical Only | Metabolic / Anti-Aging

Pancragen (Lys-Glu-Asp-Trp, KEDW) is a synthetic tetrapeptide (MW ~562.6 g/mol) from the Khavinson bioregulatory peptide family, designed as a pancreas-specific bioregulator.

Mechanism: Pancragen is proposed to interact with DNA regulatory sequences in pancreatic cells, particularly beta-cells, modulating expression of genes involved in insulin synthesis, glucose sensing, and...

Meaningful Human Data | Neuroendocrine / Approved (diagnostic)

TRH (protirelin) is a hypothalamic tripeptide that stimulates TSH and prolactin release from the anterior pituitary. It is approved as a diagnostic agent for thyroid function testing and has been studied for antidepressant and analeptic properties.

Mechanism: TRH binds to TRH receptors (TRHR1/R2) on thyrotroph and lactotroph cells in the anterior pituitary, activating Gq-coupled signaling via phospholipase C to stimulate TSH and prolactin secretion.