A Complete History of Weight Loss Drugs Through 2024

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.

According to Craig Primack, MD, FACP, FAAP, MFOMA, a physician specializing in obesity medicine and senior vice president of weight loss at Hims & Hers, it wasn’t until 1959, when the FDA approved phentermine, that weight loss treatments began to turn a corner.

“That was really the beginning of the modern-day medical treatments for obesity,” says Dr. Primack. 

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. 

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 lead to overactive thyroid.

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 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. 

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 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.

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.

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.

(Related: Ozempic® vs Metformin For Weight Loss)

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. 

Dr. Primack explains that while on orlistat, “Your body doesn’t know the difference between passing gas and an oily diarrhea. So you would soil yourself and have to go home and change your clothes.”

(Related: Protein for Weight Loss: How Much Protein Should You Eat?)

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.

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.

(Related: Wegovy vs. Ozempic for Weight Loss)

In recent years, other weight loss treatment options that include a combination of medications have entered the market. In 2023, Hims & Hers launched a weight management program that includes a personalized combination of medications such as bupropion, metformin, topiramate, naltrexone, and vitamin B.

“Different medicines work on different parts of the brain,” says Dr. Primack.

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, like those offered in the Hims & Hers app, allows people to address weight loss more holistically. 

The complete history of weight loss drugs is one of research and development. 

“We’ve gone from medicines that had lots of side effects and low efficacy,” says Dr. Primack, to those that have “less side effects and high efficacy.”

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.