The weight loss medications on the market today are generally approved for adults with obesity who have a body mass index (BMI) of 30 or higher, or adults with a BMI of 27 or greater who have at least one weight-related health problem such as high blood pressure, type 2 diabetes, or high cholesterol.
But until recently, very few patients who met those criteria took drugs to lose weight. One study collected prescription data from more than 2.2 million adults eligible for treatment with weight loss medications from 2009 to 2015.
Part of the problem came down to safety concerns, particularly because so many of the first drugs used for weight loss decades ago had potentially life-threatening side effects.
As far back as the 1940s, cocktails of appetite suppressants known as “rainbow pills” were heavily marketed to American women.
The brightly colored capsules often contained amphetamines, diuretics, laxatives, and thyroid hormones to maximize weight loss. They were typically mixed with drugs like benzodiazepines, barbiturates, and antidepressants. By the 1960s, after those potent cocktails of drugs had caused dozens of deaths, the U.S. Food and Drug Administration (FDA) removed them from the market.
“None of these medications were tested in long-term trials prior to repurposing them for the treatment of obesity. This raises the risk that they will have side effects not recognized in short-term therapy,” says Frank Greenway, MD, the chief medical officer and a professor at the Pennington Biomedical Research Center at Louisiana State University in Baton Rouge.
In the 1990s, another untested weight loss cocktail nicknamed fen-phen started taking off.
This cocktail mixed the psychiatric drug fenfluramine, which boosts levels of the brain chemical serotonin and induces feelings of satiety, with the appetite suppressant phentermine. An older version of fenfluramine, marketed as Pondimin, was on the market for more than two decades, and a newer version called dexfenfluramine, marketed as Redux, was sold for about a year, before both were recalled in 1997 because of concerns that the products caused heart valve defects.
An appetite suppressant called sibutramine, marketed as Meridia, was recalled by the FDA in 2010 after more than a decade on the market, because of an increased risk of cardiovascular events and strokes.
Next up, the prescription weight loss drug lorcaserin (Belviq) was recalled by the FDA over cancer concerns in 2020, after more than a decade on the market.