This timeline documents the major milestones in peptide drug approval, from the first peptide therapeutic (insulin) in 1922 to modern GLP-1 receptor agonists and beyond.
| Year | Peptide | Indication | Agency | Significance |
|---|
| 1922 | Insulin (animal) | Type 1 diabetes | FDA | First peptide therapeutic |
| 1955 | Vasopressin (Pitressin) | Diabetes insipidus | FDA | First synthetic neuropeptide |
| 1962 | Oxytocin (Pitocin) | Labor induction | FDA | First synthetic reproductive peptide |
| 1966 | Calcitonin (salmon) | Paget’s disease | FDA | First peptide for bone disease |
| 1972 | Insulin (human) | Diabetes | FDA | First recombinant peptide |
| 1978 | Insulin (Humulin) | Diabetes | FDA | First recombinant DNA product |
| 1979 | Desmopressin (DDAVP) | Diabetes insipidus | FDA | Synthetic vasopressin analogue |
| Year | Peptide | Indication | Agency | Significance |
|---|
| 1982 | Insulin (Humulin) | Diabetes | FDA | First recombinant DNA drug |
| 1985 | Calcitonin (Miacalcin) | Osteoporosis | FDA | Nasal calcitonin |
| 1986 | Growth hormone (Protropin) | GH deficiency | FDA | First recombinant hGH |
| 1987 | Insulin-like growth factor-1 | GH insensitivity | FDA | First recombinant IGF-1 |
| 1988 | Calcitonin (Miacalcin) | Hypercalcemia | FDA | Expanded calcitonin indication |
| 1989 | Growth hormone (Humatrope) | GH deficiency | FDA | Second-generation hGH |
| Year | Peptide | Indication | Agency | Significance |
|---|
| 1990 | Leuprolide (Lupron) | Prostate cancer | FDA | GnRH agonist for oncology |
| 1991 | Octreotide (Sandostatin) | Acromegaly | FDA | First somatostatin analogue |
| 1993 | Goserelin (Zoladex) | Breast cancer | FDA | GnRH agonist implant |
| 1995 | Epoprostenol (Flolan) | PAH | FDA | First prostacyclin for PAH |
| 1996 | Insulin lispro (Humalog) | Diabetes | FDA | First rapid-acting analogue |
| 1997 | Glucagon | Hypoglycemia | FDA | Recombinant glucagon |
| 1998 | Insulin aspart (NovoRapid) | Diabetes | EMA | Rapid-acting analogue |
| 1999 | Mifepristone (RU-486) | Medical abortion | FDA | Steroidal (not peptide) |
| Year | Peptide | Indication | Agency | Significance |
|---|
| 2000 | Insulin glargine (Lantus) | Diabetes | FDA | First long-acting analogue |
| 2001 | Insulin detemir (Levemir) | Diabetes | EMA | Fatty acid acylation |
| 2003 | Exenatide (Byetta) | T2D | FDA | First GLP-1 RA |
| 2004 | Exenatide (Byetta) | T2D | FDA | First incretin mimetic |
| 2005 | Liraglutide (Victoza) | T2D | EMA | Once-daily GLP-1 RA |
| 2006 | Insulin glulisine (Apidra) | Diabetes | FDA | Third rapid-acting analogue |
| 2007 | Pramlintide (Symlin) | T1D | FDA | First amylin analogue |
| 2008 | Liraglutide (Victoza) | T2D | FDA | GLP-1 RA approval |
| 2009 | Dulaglutide (Trulicity) | T2D | FDA | Once-weekly GLP-1 RA |
| 2010 | Tesamorelin (Egrifta) | HIV lipodystrophy | FDA | First GHRH analogue |
| Year | Peptide | Indication | Agency | Significance |
|---|
| 2012 | Lixisenatide (Lyxumia) | T2D | EMA | GLP-1 RA (once-daily) |
| 2012 | Insulin degludec (Tresiba) | Diabetes | EMA | Ultra-long-acting insulin |
| 2014 | Semaglutide (Ozempic) | T2D | FDA | Once-weekly GLP-1 RA |
| 2014 | Tirzepatide (Mounjaro) | T2D | FDA | Dual GIP/GLP-1 RA |
| 2017 | Semaglutide (Wegovy) | Obesity | FDA | GLP-1 RA for weight management |
| 2018 | Insulin icodec (Novo Nordisk) | Diabetes | Phase III | Weekly basal insulin |
| 2019 | Afamelanotide (Scenesse) | EPP | FDA | First melanocortin analogue |
| 2019 | Semaglutide (Rybelsus) | T2D | FDA | First oral GLP-1 RA |
| 2020 | Tirzepatide (Zepbound) | Obesity | FDA | Dual agonist for obesity |
| 2021 | Semaglutide (Wegovy) | Obesity | FDA | Expanded obesity indication |
| 2022 | Orforglipron | T2D | Phase III | Oral non-peptide GLP-1 RA |
| 2023 | Heat-stable carbetocin | PPH | WHO PQ | Heat-stable uterotonic |
| Year | Peptide | Indication | Agency | Status |
|---|
| 2024 | Retatrutide | Obesity/T2D | Phase III | Triple agonist (GLP-1/GIP/glucagon) |
| 2024 | Survodutide | Obesity/MASH | Phase III | Dual agonist (GLP-1/glucagon) |
| 2025 | Cagrilintide + semaglutide | Obesity | Phase III | Amylin + GLP-1 RA combination |
| 2025 | Amycretin | Obesity | Phase II | Dual GLP-1/amylin agonist |
| 2025 | Pemvidutide | Obesity | Phase II | Dual GLP-1/glucagon agonist |
| 2026E | Orforglipron | T2D/Obesity | FDA submission | Oral GLP-1 RA |
| 2026E | Retatrutide | Obesity | FDA submission | Triple agonist |
| Milestone | Year | Peptide |
|---|
| First peptide therapeutic | 1922 | Insulin |
| First recombinant DNA drug | 1982 | Humulin |
| First GLP-1 receptor agonist | 2003 | Exenatide |
| First amylin analogue | 2007 | Pramlintide |
| First oral GLP-1 RA | 2019 | Semaglutide (Rybelsus) |
| First melanocortin analogue | 2019 | Afamelanotide |
| First heat-stable uterotonic | 2023 | Carbetocin |
| Class | First Approval | Key Agent | Current Leader |
|---|
| Insulins | 1922 | Insulin (animal) | Degludec/Tirzepatide |
| GnRH analogs | 1990 | Leuprolide | Leuprolide/Goserelin |
| Somatostatin | 1991 | Octreotide | Octreotide/Lanreotide |
| GLP-1 RAs | 2003 | Exenatide | Semaglutide |
| GIP/GLP-1 | 2014 | Tirzepatide | Tirzepatide |
| Amylin analogues | 2007 | Pramlintide | Cagrilintide |
| Melanocortins | 2019 | Afamelanotide | Afamelanotide |
| Peptide | Company | Indication | Expected |
|---|
| Retatrutide | Eli Lilly | Obesity | 2026 |
| Survodutide | Boehringer | MASH | 2026 |
| Orforglipron | Eli Lilly | T2D/Obesity | 2026 |
| Amycretin | Novo Nordisk | Obesity | 2027 |
| Cagrilintide + semaglutide | Novo Nordisk | Obesity | 2025 |
| Pemvidutide | Altimmune | Obesity | 2027 |
| Danuglipron | Pfizer | T2D | 2026 |
The history of peptide drug approvals spans over a century, from the first insulin extract in 1922 to modern GLP-1 receptor agonists and next-generation multi-agonists. Key milestones include the recombinant DNA revolution (1980s), GnRH and somatostatin analogues (1990s), and the incretin revolution (2000s–present). The GLP-1 RA class has become the dominant force in peptide therapeutics, with semaglutide and tirzepatide leading a new generation of peptides targeting metabolic disease. The pipeline includes triple agonists, oral non-peptide GLP-1 RAs, and combination approaches that promise to further transform the treatment of obesity, diabetes, and cardiovascular disease.
