Phentermine approved
Phentermine received its first US approval, labeled for short-term use of a few weeks.[1]
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History
From phentermine in 1959 to semaglutide and tirzepatide: the discoveries and approvals that made the treatment.
Timeline
Phentermine received its first US approval, labeled for short-term use of a few weeks.[1]
Two groups showed that GLP-1 (7-37), a peptide cut from proglucagon, strongly stimulates insulin release. Holst's group isolated it from pig intestine as a hormone of the distal gut.[1][2]
Eng's group isolated exendin-4, a 39-amino acid peptide, from the venom of Heloderma suspectum, the Gila monster.[1]
Connolly reported valvular heart disease in 24 women treated with fenfluramine-phentermine. US prescriptions for the pair exceeded 18 million in 1996.[1]
Byetta (exenatide), a 39-amino acid incretin mimetic, was labeled for blood sugar control in type 2 diabetes.[1]
COR-I reported 6.1% weight loss with naltrexone-bupropion in 2010. CONQUER reported 9.8% with phentermine-topiramate in 2011.[1][2]
Phentermine-topiramate extended-release was approved for chronic weight management, dispensed under a REMS because of the risk of oral clefts.[1]
Liraglutide 3 mg (Saxenda), a daily GLP-1 injection, was approved for chronic weight management. Naltrexone-bupropion (Contrave) was approved the same year.[1][2][3]
Lau's team reported semaglutide, designed for once-weekly dosing through stronger albumin binding, with a 46 hour half-life in mini-pigs. The same year SCALE reported 8.4 kg loss on liraglutide.[1][2]
Semaglutide received its first US approval as Ozempic for type 2 diabetes.[1]
STEP 1 reported 14.9% weight loss with semaglutide 2.4 mg weekly. The FDA approved it as Wegovy for chronic weight management the same year.[1][2][3]
SURMOUNT-1 reported up to 20.9% weight loss with tirzepatide. Mounjaro was approved for type 2 diabetes. Tirzepatide and semaglutide injections went into shortage.[1][2][3]
Zepbound was approved on November 8, 2023. SELECT showed a 20% lower risk of heart attack, stroke or cardiovascular death on semaglutide, and Wegovy gained that indication on March 8, 2024.[1][2][3]
FDA declared the tirzepatide shortage resolved on December 19, 2024 and the semaglutide shortage on February 21, 2025. The last grace period for compounders ended on May 22, 2025.[1]
People
Their studies set the treatments in use today.
Showed that GLP-1 (7-37), co-encoded in the glucagon gene, stimulates insulin release at very low concentrations.[1]
Isolated truncated GLP-1 from pig intestine and showed it is an insulin-releasing hormone from the distal gut.[1]
Isolated exendin-4 from Gila monster venom.[1]
Reviewed how GLP-1 acts on insulin, glucagon, gastric emptying and food intake.[1]
First author of the paper describing the design of once-weekly semaglutide.[1]
First author of SCALE, the 3,731-person trial of liraglutide 3 mg for weight management.[1]
First author of STEP 1 and its extension: 14.9% loss on semaglutide, two-thirds regained a year after stopping.[1][2]
First author of SURMOUNT-1, the 2,539-person tirzepatide obesity trial.[1]
First author of SURMOUNT-4 on maintenance and SURMOUNT-5, tirzepatide against semaglutide.[1][2]
First author of SELECT, the 17,604-person cardiovascular outcomes trial of semaglutide in obesity.[1]
First authors of CONQUER (phentermine-topiramate) and COR-I (naltrexone-bupropion).[1][2]
First author of the report of valvular heart disease in 24 women treated with fenfluramine-phentermine.[1]