Metabolic Peptides
Peptides investigated for effects on metabolism, energy, and body composition
About This Category
The metabolic peptide category encompasses the most rapidly evolving area of peptide research, driven by the clinical success of GLP-1 receptor agonists and the emergence of multi-receptor agonist compounds. These peptides act on incretin hormone receptors - GLP-1, GIP, and glucagon receptors - that coordinate glucose homeostasis, appetite regulation, gastric emptying, and energy expenditure across multiple organ systems. The gut-brain axis is a central theme, with GLP-1 receptors present in both pancreatic beta cells and hypothalamic appetite centers.
Semaglutide and liraglutide are established GLP-1 receptor agonists with robust clinical trial data. Tirzepatide introduced dual GLP-1/GIP receptor agonism, demonstrating superior efficacy in clinical trials. Retatrutide advances this further with triple GLP-1/GIP/glucagon receptor agonism, with early trials showing substantial metabolic effects. Oral small molecule GLP-1 agonists like orforglipron represent the next frontier. Beyond incretin biology, MOTS-c is a mitochondria-derived peptide that activates AMPK pathways to regulate metabolic homeostasis. AOD-9604 is a fragment of human growth hormone studied specifically for lipolytic effects without full GH receptor activation.
Amylin analogs (pramlintide, cagrilintide) complement GLP-1 action by slowing gastric emptying and suppressing glucagon. Melanocortin pathway peptides PT-141 and Melanotan-II act through MC3R/MC4R receptors that are central to both sexual function and energy balance. Teduglutide (GLP-2 analog) targets intestinal epithelial growth for short bowel syndrome. This category illustrates how peptide research translates from preclinical mechanisms to approved pharmaceuticals - several compounds here have completed Phase 3 trials.
Key Mechanisms
- GLP-1 receptor (GLP-1R) agonism
- GIP receptor (GIPR) agonism
- Glucagon receptor agonism
- Amylin receptor signaling
- AMPK/MOTS-c mitochondrial pathway
- Melanocortin receptor (MC3R/MC4R) signaling
- Gut-brain axis appetite regulation
- Lipolysis modulation via GH fragment activity
Peptides in Metabolic
PT-141
PT-141 (Bremelanotide) is a synthetic peptide that acts on melanocortin receptors. It was developed from the tanning peptide Melanotan II and has been studied for sexual dysfunction.
Melanotan II
Melanotan II is a synthetic analog of alpha-melanocyte stimulating hormone. It was developed for research into tanning, sexual function, and appetite regulation.
AOD-9604
AOD-9604 is a modified fragment of human growth hormone (amino acids 176-191) that has been studied for its effects on fat metabolism without the growth-promoting effects of full GH.
Tesamorelin
Tesamorelin is a synthetic growth hormone releasing hormone analog. It is FDA-approved for reducing excess abdominal fat in HIV-infected patients with lipodystrophy.
MOTS-c
MOTS-c is a mitochondria-derived peptide that plays a role in metabolic homeostasis. It is encoded in the mitochondrial genome and affects insulin sensitivity and cellular metabolism.
Kisspeptin
Kisspeptin is a neuropeptide that plays a central role in regulating the reproductive hormone axis. It is the endogenous ligand for the GPR54 receptor.
Semaglutide (GLP-1)
Semaglutide is a long-acting GLP-1 (glucagon-like peptide-1) receptor agonist that mimics the incretin hormone GLP-1, regulating blood glucose levels, appetite, and body weight through multiple metabolic pathways.
Liraglutide (GLP-1)
Liraglutide is a GLP-1 receptor agonist with 97% amino acid sequence homology to native GLP-1, modified with a palmitic acid chain for extended duration of action, used in research for diabetes and obesity.
Teduglutide (GLP-2)
Teduglutide is a GLP-2 (glucagon-like peptide-2) analog that promotes intestinal mucosal growth and function, FDA-approved for short bowel syndrome research and treatment.
Tirzepatide (GLP-1/GIP)
Tirzepatide is a first-in-class dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptor agonist, providing synergistic metabolic effects for diabetes and obesity research.
Retatrutide (Triple Agonist)
Retatrutide is a first-in-class triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously, producing the most profound metabolic effects seen in obesity research to date.
Orforglipron
Orforglipron is an oral, non-peptide GLP-1 receptor agonist developed by Eli Lilly and approved by the FDA in April 2026 as Foundayo for chronic weight management. It enables once-daily oral dosing of a small molecule that mimics incretin hormone activity, without the food and water restrictions of oral peptide GLP-1 drugs.
Survodutide
Survodutide is a dual glucagon and GLP-1 receptor agonist developed by Boehringer Ingelheim and Zealand Pharma, investigated for obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH).
Cagrilintide
Cagrilintide is a long-acting acylated amylin analog developed by Novo Nordisk, designed for once-weekly subcutaneous administration and studied both as monotherapy and in combination with semaglutide (CagriSema) for obesity and type 2 diabetes management.
Mazdutide
Mazdutide is a dual GLP-1 and glucagon receptor agonist based on an oxyntomodulin analog, developed by Innovent Biologics in partnership with Eli Lilly, and the first drug of its class to receive regulatory acceptance for obesity in China.
Pramlintide
Pramlintide is a synthetic analog of the pancreatic hormone amylin, originally FDA-approved in 2005 as adjunctive therapy to mealtime insulin for type 1 and type 2 diabetes. Note: All Symlin formulations were discontinued from the US market in 2025 (NDA 021332).
SS-31
SS-31 (elamipretide) is a synthetic, cell-permeable tetrapeptide that targets the inner mitochondrial membrane and binds the phospholipid cardiolipin. It is studied as a mitochondrial bioenergetics agent and was approved by the FDA in 2025 for Barth syndrome under the brand name Forzinity.