A doctor informs fourth-grader Eric Cartman and his mother, Liane, that his obesity is a health risk. When Liane says that diet and exercise have failed, the doctor suggests a diabetes drug called semaglutide, known for weight loss. Cartman dreams of insulting people without being mocked for his weight, even fantasizing about going to Pakistan. However, insurance only covers the drug for diabetes, making it too expensive for Liane. The doctor then prescribes listening to Lizzo’s music, which promotes body positivity.
Despondent, Cartman, along with friends Butters Stotch and Kyle Broflovski, visits an insurance office to make a claim but gets tangled in the healthcare bureaucracy. They decide to make semaglutide themselves by buying the raw powder cheaply from India and mixing it with biostatic water. Friends Stan Marsh and Kenny McCormick join the plan.
Meanwhile, Randy Marsh notices local mothers flaunting toned midriffs from using semaglutide. Randy, thinking it’s a harmless party drug, starts using it himself, causing his wife Sharon to feel self-conscious. She starts listening to Lizzo, leading to “diabeardes” (diabetes affecting the ears), qualifying her for semaglutide, which her doctor prescribes.
Seeing success with homemade semaglutide curbing Cartman’s appetite, Kyle decides to produce more for those who can’t afford it. This angers a sugar industry cartel represented by breakfast cereal and sugary snack mascots. A government crackdown on semaglutide abuse drives the mothers and Randy to rob pharmacies and then Kyle and his friends. The boys’ supply is destroyed when sugar mascots attack the Indian factory, murdering workers and burning it down.
Kyle buys a truckload of semaglutide powder from North Carolina, but it’s carjacked by Randy and the mothers. Realizing their actions are wrong, Randy steals the truck back. A violent chase ensues, involving the boys and the sugar mascots. Kenny is killed, and when they finally open the truck, they find only the insurance claims agent, who informs them of another round through the healthcare system.
Before Sharon takes her first semaglutide injection, Randy stops her, admitting his own use. Realizing how cool she is, he invites her to a Holiday Inn to take MDMA together as they did in college. Meanwhile, Kyle calls for an end to fat shaming in a school speech, garnering positive reactions. Overjoyed, Cartman insults his classmates without being mocked for his weight and books a flight to Pakistan to continue this.