Peptides Studied for Weight Management

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. It is approved for type 2 diabetes (Ozempic), chronic weight management (Wegovy), and non-cirrhotic MASH (Wegovy). Developed by Novo Nordisk and first FDA-approved December 5, 2017, it is backed by the extensive STEP and SUSTAIN trial programs involving thousands of patients. There is no generic semaglutide available, and the FDA has warned about counterfeit products.

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. It is a 39-amino-acid peptide with a C20 fatty di-acid moiety that promotes albumin binding, enabling once-weekly dosing. Clinical trials consistently demonstrate it delivers the most substantial weight reduction among incretin-based therapies, with up to 22.5% mean body weight loss at 72 weeks.

Tesamorelin (tesamorelin acetate) is a synthetic 44-amino-acid analog of human growth hormone-releasing hormone (GHRH) and the only FDA-approved medication for reducing excess abdominal fat in HIV-infected adults with lipodystrophy, marketed as Egrifta. It stimulates endogenous GH and IGF-1 production. Egrifta WR, a new weekly-reconstitution formulation, was FDA-approved in March 2025. Phase 3 trials demonstrated significant visceral fat reduction with a generally well-tolerated safety profile over 26 weeks of therapy.

SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane, binding to cardiolipin and stabilizing cristae structure. It is being developed by Stealth BioTherapeutics for mitochondrial diseases, heart failure, and age-related mitochondrial dysfunction. It has undergone multiple Phase I–III clinical trials, including the TAZPOWER trial for Barth syndrome.

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. It was the first GLP-1 agonist approved for obesity. While effective, it has been largely superseded by semaglutide (once-weekly dosing, greater weight loss) — liraglutide requires daily injection and achieves approximately 8% weight loss vs semaglutide's 15%.

Exenatide is a 39-amino-acid GLP-1 receptor agonist (MW ~4186.6 g/mol) originally derived from exendin-4, a peptide found in the saliva of the Gila monster (Heloderma suspectum). It was the first GLP-1 receptor agonist approved by the FDA, with Byetta (twice-daily injection) approved in April 2005 and Bydureon (once-weekly extended-release) approved in January 2012, both for type 2 diabetes. Exenatide shares approximately 53% sequence homology with human GLP-1 and is resistant to DPP-4 degradation.

Dulaglutide (brand name Trulicity) is a once-weekly GLP-1 receptor agonist developed by Eli Lilly, FDA-approved in September 2014 for type 2 diabetes. It is a fusion protein consisting of a GLP-1 analog covalently linked to a modified human IgG4 Fc fragment via a small peptide linker (MW ~59,670 g/mol). The Fc fusion extends its half-life to approximately 5 days, enabling once-weekly dosing. Dulaglutide is administered via a single-dose pen device that does not require reconstitution.

Lixisenatide is a once-daily GLP-1 receptor agonist (MW ~4858.5 g/mol) based on the exendin-4 scaffold, with a modified C-terminal tail containing six lysine residues. It was developed by Sanofi and FDA-approved in July 2016 (Adlyxin) for type 2 diabetes. It is also marketed as Lyxumia outside the United States. Lixisenatide is available in a fixed-ratio combination with insulin glargine as Soliqua 100/33.

Albiglutide (brand name Tanzeum in the US, Eperzan in Europe) was a once-weekly GLP-1 receptor agonist consisting of two copies of a modified GLP-1 sequence fused to human albumin (MW ~72,970 g/mol). Developed by GlaxoSmithKline, it was FDA-approved in April 2014 for type 2 diabetes. GSK voluntarily withdrew Tanzeum from the market in July 2018 for commercial reasons (low market uptake), not due to safety concerns. The HARMONY Outcomes trial subsequently demonstrated cardiovascular benefit.

Pramlintide (brand name Symlin) is a synthetic analog of amylin, a 37-amino-acid pancreatic hormone co-secreted with insulin from beta cells (MW ~3949.4 g/mol). FDA-approved in March 2005, it is the only amylin analog approved for clinical use and is indicated as adjunctive therapy for type 1 and type 2 diabetes patients on mealtime insulin who have failed to achieve adequate glycemic control. Pramlintide has three proline substitutions (positions 25, 28, 29) that prevent the amyloid aggregation inherent to native human amylin.

Calcitonin (salmon) is a synthetic 32-amino-acid peptide hormone (MW ~3431.9 g/mol) identical to calcitonin produced by the ultimobranchial glands of salmon. It is FDA-approved for the treatment of postmenopausal osteoporosis (nasal spray), hypercalcemia of malignancy (injection), and Paget disease of bone (injection). Salmon calcitonin is approximately 40-50 times more potent than human calcitonin at inhibiting osteoclast activity. It is no longer a first-line therapy for osteoporosis due to the availability of more effective agents and a potential cancer risk signal.

Setmelanotide (brand name Imcivree) is a cyclic 8-amino-acid peptide (MW ~1117.3 g/mol) that acts as a melanocortin 4 receptor (MC4R) agonist. FDA-approved in November 2020 by Rhythm Pharmaceuticals, it is the first-ever treatment for chronic weight management in patients aged 6 years and older with monogenic or syndromic obesity due to POMC, PCSK1, or LEPR deficiency confirmed by genetic testing. It was subsequently approved for Bardet-Biedl syndrome (BBS) in June 2022. Setmelanotide directly restores MC4R signaling downstream of the defective leptin-melanocortin pathway.

Macimorelin (Macrilen) is an orally active growth hormone secretagogue that received FDA approval in December 2017 as a diagnostic test for adult growth hormone deficiency (AGHD). It is the only FDA-approved oral GH secretagogue in the United States. Macimorelin works by stimulating GH release; the peak GH response is then measured to diagnose GH deficiency. It was developed by Aeterna Zentaris. Novo Nordisk held U.S. and Canadian marketing rights from 2018 until returning them to Aeterna Zentaris in 2022. Clinical trials demonstrated 92% concordance with the insulin tolerance test (ITT), the previous gold standard.

Human growth hormone (hGH, somatotropin) is a 191-amino acid protein produced by the anterior pituitary gland. Recombinant human growth hormone (rhGH, somatropin) is FDA-approved for numerous indications including pediatric and adult growth hormone deficiency, Turner syndrome, short stature from small for gestational age (SGA), Prader-Willi syndrome, chronic kidney disease, idiopathic short stature, and short bowel syndrome (Zorbtive). It is one of the most extensively studied hormones in medicine. Off-label use for anti-aging and performance enhancement is widespread but not approved, and GH is banned by WADA in sport.

Insulin-like Growth Factor 1 (IGF-1) is a 70-amino acid protein structurally similar to insulin. It is primarily produced by the liver in response to growth hormone stimulation and mediates many of GH's growth-promoting effects. Recombinant human IGF-1 (mecasermin, brand name Increlex) is FDA-approved for the treatment of severe primary IGF-1 deficiency (primary IGFD) — a condition where patients have normal or elevated GH but fail to produce adequate IGF-1. IGF-1 plays critical roles in growth, development, and metabolism throughout life. It circulates bound to IGF binding proteins (primarily IGFBP-3 in a ternary complex with acid-labile subunit).

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. It was the first somatostatin analog approved by the FDA (1988) and is available as both an immediate-release subcutaneous injection (Sandostatin) and a long-acting intramuscular depot formulation (Sandostatin LAR). Octreotide is FDA-approved for acromegaly, severe diarrhea associated with carcinoid tumors, and VIPomas (vasoactive intestinal peptide-secreting tumors).

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). It is FDA-approved for acromegaly and for the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lanreotide self-assembles into nanotubes at high concentration, enabling sustained drug release over 4 weeks from a single injection.

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). It is FDA-approved for Cushing disease (Signifor SC, 2012) and acromegaly in patients inadequately controlled on first-generation somatostatin analogs (Signifor LAR, 2014). Pasireotide is the first pituitary-directed medical therapy approved specifically for Cushing disease.

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. It is FDA-approved for the emergency treatment of severe hypoglycemia and as a diagnostic aid for GI radiographic examination. Multiple formulations are available: traditional reconstituted injection (GlucaGen), intranasal powder (Baqsimi, approved 2019), and ready-to-use auto-injector (Gvoke, approved 2019), representing significant advances in emergency usability.

Afamelanotide is a 13-amino-acid synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH) with a molecular weight of approximately 1646.9 g/mol. It was FDA-approved in October 2019 (Scenesse) to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria (EPP). Afamelanotide is administered as a subcutaneous implant that releases the peptide over approximately 10 days, stimulating eumelanin production to provide photoprotection.