FDA clears Plenity, a hydrogel weight-management device, for adults with BMI 25 to 40

The FDA cleared Plenity, an oral hydrogel weight-management product made by Gelesis, in April 2019. It is regulated as a medical device rather than a drug, and it is indicated for adults with a body mass index of 25 to 40 who use it along with diet and exercise ^[1][2][3].

TIME initially reported that the FDA had approved Plenity and later published a correction saying it was cleared as a device for weight management, not approved as a drug for weight loss ^[1]. The distinction reflects how the product works: it acts mechanically in the stomach and does not enter the bloodstream, which is why it went through the device pathway ^[1][2]. TIME described the clearance as covering adults with a BMI of at least 25 ^[1]; the labeled indication in a later clinical review and on the company's website is a BMI of 25 to 40 ^[2][3].

How it works and what the trial found

Each capsule contains thousands of particles made of modified cellulose cross-linked with citric acid. Taken with 500 milliliters of water 20 to 30 minutes before lunch and dinner, the capsules break apart in the stomach and the particles absorb water to form a gel ^[2]. Fully hydrated, the particles occupy about one-fourth of a person's stomach volume and mix with food, promoting fullness ^[1][2]. The gel travels through the small intestine, partially breaks down in the large intestine, and the remaining cellulosic material is expelled in feces ^[2]. "It creates a sense of satiety, but it's not a compound that enters the bloodstream and goes to the brain," said Dr. Caroline Apovian, director of nutrition and weight management at Boston Medical Center, who has studied the product in Gelesis-sponsored research ^[1].

In the GLOW study, 436 adults were randomly assigned to Plenity (223) or placebo (213) for 24 weeks. Mean age was 48 and mean BMI was 34, and everyone also followed a diet 300 calories below their calculated daily requirement and was told to exercise at moderate intensity daily ^[2]. Mean weight loss was 6.4% with Plenity versus 4.4% with placebo (P=0.0007) ^[1][2]. Fifty-nine percent of the treatment group lost at least 5% of body weight versus 42% on placebo, and 27% lost at least 10% versus 15% ^[2]. Gelesis describes that 59% as "responders" who lost an average of about 10% of their weight, or 22 pounds, and says 26% were "super-responders" who lost an average of 14%, or 30 pounds ^[3].

In a 48-week extension, 39 patients from GLOW enrolled. Those who kept taking Plenity had lost a mean of 7.6% of body weight at 48 weeks, up from 7.1% at 24 weeks; those switched from placebo to Plenity had lost 9.4% by 48 weeks ^[2]. Among 32 Plenity and 36 placebo participants with prediabetes or drug-naive type 2 diabetes and an A1C below 8.5%, mean weight change was -8.1% versus -5.6% ^[2].

The most common side effects were gastrointestinal: diarrhea, bloating, infrequent bowel movements and flatulence, generally mild or moderate and more frequent than with placebo (P=0.02) ^[2][3]. The company reported no overall increase in adverse events versus placebo and no serious adverse events ^[3]. Plenity is contraindicated in pregnancy and in people allergic to its components, including cellulose, citric acid, sodium stearyl fumarate, gelatin and titanium dioxide, and should be avoided by people with esophageal abnormalities, suspected strictures such as Crohn's disease, or previous gastrointestinal surgery that may have altered motility; caution is advised with GERD, ulcers or heartburn ^[2][3]. Gelesis advises taking medications that must be taken with food after starting a meal, and medications taken on an empty stomach at least two hours before or after Plenity and a meal ^[3].

Why it matters for patients

Most prescription weight-loss drugs are limited to people with a BMI of 30 or above or with weight-related health conditions. Plenity's indicated range starts at 25 and does not require another condition, and TIME reported it can be taken alongside other weight-loss medications ^[1][2][3]. "Right now, between a BMI of 25 and 30 we have a big treatment gap," Apovian said ^[1].

The trial's average result was modest, 6.4% versus 4.4%, and the placebo group also lost weight while dieting and exercising ^[2]. Results varied widely between individuals, which is why the company separates responders from the rest of the group ^[3]. Plenity is nonsystemic, meaning it does not enter the bloodstream, a category that did not previously exist for weight management ^[1][2].

Pricing had not been disclosed when the clearance was announced. A Gelesis representative told TIME the company was "committed to making sure Plenity is affordable for consumers out-of-pocket, even if their insurance does not cover it" ^[1]. Whether insurers cover it has not been disclosed.

What happens next

Gelesis said a limited launch was expected in the second half of 2019, with widespread availability slated for 2020 ^[1]. A clinical review published in July 2020 said Plenity was not yet available when the review was written, and that no cost information was available ^[2].