A comprehensive history of weight loss drugs through the latest injections

Caroline Ruda // Shutterstock Humans have spent thousands of years experimenting with weight loss aids. While Ozempic and Wegovy may be generating headlines today, they have a long list of less successful (and sometimes dangerous) predecessors.   Back in the days of the Greek physician Hippocrates (460-377 BCE), practitioners recommended various plants, berries, and natural remedies for weight loss. These treatments were intended to produce nausea, vomiting, and diarrhea.  Weight loss treatments have come a long way since then. Hims & Hers reports that when the FDA approved phentermine in 1959, weight loss treatments began to turn a corner. But the road to today’s treatment options has been long, bumpy, and polluted by those who prioritize weight loss over health and safety.  The following timeline of weight loss medications covers the historical progression of weight loss drugs throughout the ages.  The 19th and Early 20th Century In the late 1800s, physicians began using thyroid hormones to treat obesity. Originally intended for people with underactive thyroid, doctors believed these drugs could support weight loss. Many medical professionals voiced strong opposition when it became clear that these treatments led to overactive thyroid. The 1940s The 1940s marked the beginning of amphetamine use for weight loss. Amphetamines are stimulants that boost energy and decrease appetite. But medical professionals soon discovered these drugs, including methamphetamines, came with a high potential for addiction.   The 1950s The FDA approved a new central nervous system stimulant called phentermine for weight loss in 1959. As an amphetamine analogue, phentermine, which is still in use today, has a lower risk of dependence than its predecessor.  Today, phentermine is combined with a medication called topiramate and sold under the brand name Qsymia. This medication works to reduce hunger. When combined with physical activity, it may help maintain a calorie deficit to support weight loss goals.  The 1960s In 1960, the FDA approved the oral tablet Didrex (benzphetamine hydrochloride), a central nervous system stimulant that can promote weight loss. It was also during the 1960s that Congress passed several drug safety laws, including the Kefauver Harris Amendments. For the first time, drug companies had to submit evidence showing the efficacy and safety of new drug products.  This is why Saxenda and similar weight loss injections today must meet strict regulatory standards before going to market. The 1970s The FDA approved Bontril PDM (phendimetrazine tartrate) in 1976 for the treatment of obesity. It is a phenylalkylamine sympathomimetic amine that stimulates the central nervous system. But these medications have been associated with an increased risk of pulmonary hypertension, a rare and life-threatening disorder.  Phendimetrazine is an oral tablet that remains available as a prescription, but it’s not as popular as phentermine. During the 1970s, the FDA also approved fenfluramine, an oral tablet commonly used as an appetite suppressant at that time. The 1980s Over-the-counter appetite suppressants containing phenylpropanolamine (PPA) became more popular in the 1980s. PPA had long been used as a nasal decongestant, but an expert FDA panel recognized it as generally safe and effective for weight control in 1982.  The FDA later withdrew approval of those weight loss medications amid safety concerns. Drug companies eventually discontinued PPA because of its association with an increased risk of hemorrhagic stroke. The 1990s A short-lived weight loss medication emerged in the 1990s with the introduction of fen-phen–the combination of fenfluramine with phentermine. Evidence linking fen-phen to valvular heart disease led to fen-phen’s quick demise.  Today, phentermine still plays an active role in the treatment of obesity as one of the active ingredients in Qsymia. In 1997, the FDA approved the weight loss drug Meridia (sibutramine hydrochloride monohydrate). But Meridia lost the FDA’s blessing when clinical trial data linked the drug to an increased risk of heart attack and stroke. In the 1990s, the FDA also approved metformin, an oral medication, for the treatment of type 2 diabetes. Metformin is regularly used today to help promote weight loss in people with obesity. The 2000s In 2005, the FDA approved the very first GLP-1 agonist to treat people with type 2 diabetes. The approval of the first GLP-1 injectable medication was a huge development and game-changer for weight loss treatment. Initially, weight loss was only noted as a potential side effect of the drug. Clinical trials for exenatide demonstrated the potential of this diabetes drug for weight loss.  Exenatide paved the way for future GLP-1s, providing new treatment options for people with obesity. Meanwhile, Alli (orlistat) oral capsules became available over-the-counter in 2007.   Orlistat inhibits the absorption of dietary fats, which can promote weight loss. But common side effects include oily rectal discharge, passing gas with oily discharge, and the urgent need to have a bowel movement. The unfortunate side effects of orlistat soon became known as the Alli-oops.  The 2010s More FDA-approved GLP-1 agonists entered the market during the 2010s, including the following: Victoza injections for diabetes (2010) Saxenda injections for obesity (2014) Ozempic injections for diabetes (2017) Rybelsus tablets for diabetes (2019) The FDA in 2014 approved Contrave tablets as a weight loss treatment featuring naltrexone (an opioid antagonist) and bupropion (an antidepressant) as active ingredients. The 2020s Next-generation GLP-1s entered the market in the 2020s, including the following injectable medications: Wegovy for weight loss (2021) Mounjaro for diabetes (2022) Zepbound for weight loss (2023) The active ingredient in Wegovy (semaglutide) is the same active ingredient in Ozempic and Rybelsus. The difference is that weekly Ozempic injections and daily Rybelsus tablets are not approved for weight management. Even so, physicians may prescribe Ozempic and Rybelsus off-label for weight loss. In recent years, other weight loss treatment options that include a combination of medications have entered the market.  Doctors sometimes prescribe off-label medications to help support weight loss goals. When you take an off-label drug, you’re taking it for something other than what it was FDA-approved to treat. For example, metformin is FDA-approved for the treatment of type 2 diabetes, but it can be prescribed off-label to treat obesity.  And pairing the medication with nutrition plans and behavioral programs allows people to address weight loss more holistically.  The Upshot The complete history of weight loss drugs is one of research and development.  People with obesity now have multiple treatment options available to them. And changing societal perceptions of weight loss drugs have encouraged more people to make use of these weight loss tools.  Future weight loss drugs may continue to push the envelope for treating obesity with innovative and exciting solutions. This story was produced by Hers and reviewed and distributed by Stacker Media.