Insulin sensitivity, body weight, GLP-1 axis
Metabolism.
Incretins, GLP-1 agonists and GH fragments investigated in the context of type 2 diabetes, obesity and metabolic syndrome. Includes both approved medicines and experimental substances.
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Semaglutid
Semaglutide
Semaglutide is a synthetic analog of the body's own incretin hormone GLP-1 (glucagon-like peptide-1). It binds with high affinity to the GLP-1 receptor in the pancreas, CNS and peripheral tissue. In the pancreas, it enhances glucose-dependent insulin secretion and inhibits glucagon release. In the hypothalamus, effects on satiety centres and food intake have been described. Through chemical modifications (a C18 fatty-acid side chain), semaglutide binds reversibly to albumin, which extends the half-life to about 7 days and enables once-weekly administration.
Tirzepatid
Tirzepatide
Tirzepatide is a dual agonist at GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors. It is a synthetic 39-amino-acid peptide with a C20 fatty-acid side chain that enables binding to albumin and thus a half-life of about 5 days. The simultaneous activation of both incretin receptors is intended to produce synergistic effects on insulin secretion, glucagon inhibition and food intake compared with pure GLP-1 agonists. GIP-receptor agonism has additionally been described to have direct effects on adipose tissue.
Retatrutid
Retatrutide
Retatrutide is a triple agonist at GIP, GLP-1 and glucagon receptors (GGG agonist). The additional activation of the glucagon receptor compared with dual GIP/GLP-1 agonists such as tirzepatide is intended to increase basal metabolic rate and intensify hepatic fat metabolism. Eli Lilly developed the peptide with the aim of addressing all three incretin receptors simultaneously. The selectivity and ratio of receptor activation were chosen so as to minimise hyperglycaemia from glucagon agonism.
Tesamorelin
Tesamoreline
Tesamorelin is a synthetic analog of human GHRH (growth hormone-releasing hormone), consisting of the complete GHRH(1-44) peptide with a trans-3-hexenoic acid modification at the N-terminus. This modification increases stability against enzymatic degradation by dipeptidyl peptidase IV (DPP-IV). Tesamorelin stimulates pituitary GH secretion in a physiological, pulsatile manner, as it preserves the endogenous feedback regulation via IGF-1 and somatostatin. Unlike exogenous GH, the physiological regulatory mechanism remains intact.
MOTS-c
Mitochondrial Open Reading Frame of the 12S rRNA-c
MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome — one of few known peptides of mitochondrial origin. It is transcribed and translated from the 12S ribosomal RNA gene. In preclinical studies, MOTS-c has been described as circulating in cells and in the blood, able to translocate to the cell nucleus and there modulate gene expression programmes that regulate metabolic adaptation. A postulated mechanism is activation of the AMPK signalling pathway (AMP-activated protein kinase) — a central regulator of energy metabolism. Blood MOTS-c levels decline with age, which has generated interest for longevity research.
AOD-9604
Advanced Obesity Drug 9604
AOD-9604 is a synthetic peptide fragment corresponding to the C-terminal region of human growth hormone (hGH, amino acids 177–191). In preclinical studies, this fragment was described as mediating lipolytic (fat-degrading) effects in adipocytes without triggering the anabolic or growth-promoting effects of the full GH molecule. A postulated mechanism of action involves interactions with beta-3 adrenergic receptors on fat cells. GH receptor binding and IGF-1 stimulation are absent because the GH-binding domain is missing.
GHRP-6
Growth Hormone Releasing Peptide-6
GHRP-6 is the first synthetic growth hormone secretagogue (GHS) and the prototype of the GHRP class. As a potent GHS-R1a agonist, it triggers pulsatile GH release from the pituitary. Characteristic of GHRP-6 is a pronounced ghrelin-mimetic effect in the hypothalamus, which, alongside GH release, mediates strong appetite stimulation via NPY and AgRP neurons. This appetite effect clinically distinguishes GHRP-6 from more selective GHRPs such as ipamorelin. GHRP-6 also raises cortisol and prolactin, more strongly than GHRP-2.
Survodutid
Survodutide
Survodutide is a dual agonist at glucagon and GLP-1 receptors. The GLP-1 component promotes glucose-dependent insulin secretion and satiety, while the glucagon component is intended to increase energy expenditure and hepatic fat metabolism. The aim of this combination is weight reduction beyond that of pure GLP-1 agonists, together with a favourable effect on the liver.
Mazdutid
Mazdutide
Mazdutide is a dual agonist at GLP-1 and glucagon receptors, derived from oxyntomodulin (OXM). The GLP-1 action governs insulin secretion and appetite, while the glucagon action is intended to address energy expenditure and hepatic fat metabolism. It is being developed mainly in Asia (Innovent/Eli Lilly) for obesity and type 2 diabetes.
Cagrilintid
Cagrilintide
Cagrilintide is a long-acting analog of the hormone amylin, which is co-secreted with insulin by the beta cells of the pancreas. It acts at amylin and calcitonin receptors and influences satiety, gastric emptying and food intake. Cagrilintide is investigated primarily in combination with the GLP-1 analog semaglutide (the "CagriSema" combination) to achieve additive effects on body weight.
Somatropin (HGH)
Somatropin
Somatropin is recombinant human growth hormone (hGH), a 191-amino-acid protein that matches the body's own pituitary growth hormone in structure and action. It binds to the growth hormone receptor and mediates its effects partly directly and partly via the release of IGF-1, predominantly in the liver. Described effects include longitudinal growth (in childhood), protein synthesis, lipolysis and carbohydrate metabolism.
Erythropoetin (EPO)
Erythropoetin
Erythropoietin (EPO) is a glycosylated protein hormone (165 amino acids) produced predominantly in the kidney. It binds to the EPO receptor on erythroid progenitor cells in the bone marrow and stimulates their survival, division and maturation into red blood cells. This increases the oxygen-carrying capacity of the blood. Recombinant EPO (epoetin) mimics this physiological action.
Humanin
Humanin
Humanin is a short, mitochondrially encoded peptide (mitochondrial-derived peptide, MDP) originating from a reading-frame region of the mitochondrial 16S rRNA. It is credited with cytoprotective and anti-apoptotic properties, partly via interactions with receptor complexes and Bcl-2-associated signalling. In preclinical models humanin has been investigated in the context of neuronal protection, insulin sensitivity and aging processes. The synthetic analog HNG shows enhanced activity.
Adipotide
Adipotide
Adipotide is a peptidomimetic made of two functional parts: a targeting segment that binds prohibitin on the surface of the blood vessels of white adipose tissue, and a pro-apoptotic segment (D(KLAKLAK)₂). After binding it is intended to selectively trigger apoptosis of these vascular cells and thereby cut off the blood supply to the fat tissue. In animal models this led to a reduction in fat mass. The approach differs fundamentally from appetite- or metabolism-modulating peptides.
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