Last month, Gabie Caballero got a call from her brother inviting her to his home in Houston for a Thanksgiving feast. “As soon as he mentioned food and Thanksgiving, I felt overwhelmed,” Ms. Caballero, 46, said.

Ms. Caballero takes Mounjaro, a diabetes drug similar to Ozempic, for weight loss. She is one of many Americans gearing up to face a food-focused holiday while taking a medication that can extinguish one’s appetite.

It’s been the year of Ozempic. The drug, approved in 2017 for diabetes but now widely known for its weight-loss effects, saturated TikTok and became fodder for late night shows and tabloid headlines and even a punchline at the Oscars.

Ozempic and drugs like it radically reduce how much someone wants to, or physically can, eat. People feel fuller faster, and for many, cravings fade away. The drugs can also induce unpleasant gastrointestinal side effects: vomiting, diarrhea, constipation, queasiness that some compare to morning sickness, and stomach pain.

This all can seem fundamentally incompatible with Thanksgiving.

At its best, the holiday is a day of gratitude, gathering and indulgence — an opportunity to enjoy heaps of home-cooked food, followed by the option of unbuttoning one’s jeans or slipping into sweatpants to watch a football game.

But Thanksgiving also has a reputation for producing conflict: Many come face to face with the relatives they avoid the rest of the year, and find themselves drinking a little too much wine and arguing about politics, or worse, Tofurkey.

Tensions are high. Plates are full. Families may be quick to judge. What happens when weight loss drugs collide with Thanksgiving?

‘Why aren’t you eating?’

Last Thanksgiving was Yanet Coombes’s first major holiday since beginning Mounjaro to treat her Type 2 diabetes. She and her husband spent 10 hours preparing classic American dishes and Peruvian additions like papa a la huancaína, a spicy yellow sauce poured over potatoes, for a group of about 15 people they hosted at their home near Chicago.

When Ms. Coombes, 41, sat down to eat very small portions, an interrogation broke out at the Thanksgiving table. “There was a lot of ‘Why aren’t you eating?’ or ‘Why isn’t there more on your plate?’” she said. She batted some questions away with sarcasm and answered others, but they continued: “‘You’re not hungry?’ ‘You don’t feel like you’re missing out?’”

While other holidays draw people away from the table with religious services or gift giving, there are no such distractions on Thanksgiving, said Amy Bentley, a food historian at New York University. “It really is just the meal,” she said. “That’s it, that’s the holiday.”

The typical menu is a lineup of “very salty, very heavy, very gratifying” dishes, Dr. Bentley said, even as some Americans have reckoned with the myths at the heart of the holiday and modified the meal with additions from other cuisines.

That reality has sent many people who take Ozempic and similar drugs into preparation mode. Some are wondering whether they should tell family members that they are on the medication, to avoid hurting feelings with their smaller appetites, while others are worried about inviting judgment. On Reddit forums, there’s frantic chatter about skipping doses: Should a person sacrifice their weekly shot so they can pile on the pumpkin pie?

Dr. Scott Hagan, an assistant professor of medicine at the University of Washington who studies obesity, said patients ask him if they can skip doses of Ozempic or similar drugs before a food-focused event like Thanksgiving. He advises them not to, for a few reasons: For people with diabetes, missing a dose of Ozempic and then consuming a high-carb meal could lead to a blood sugar spike. And when people restart their doses, they can experience more intense side effects.

Those who do push through the discomfort of eating a larger amount than they have gotten used to while on the medication may experience acid reflux, he said. They may feel so full that they are in pain.

“It can be a really tough holiday,” Dr. Hagan said.

‘Eating habits are so on display’

Regina Foley, 59, said she used to look forward to Thanksgiving because it was the one day when her eating wouldn’t stand out. Now that she’s on Wegovy, this is the first year she is not getting excited about sweet potato pie with marshmallows or Pillsbury biscuits. “It’s like I can take or leave it,” she said. “It doesn’t have that surge of adrenaline and anticipation like it used to.”

Her 21-year-old daughter, Maeve, is also taking the drug. She started a few months after her mother, who had gushed about how the medication cut down on her spiraling thoughts about food.

Maeve was used to confiding in her mother about her meal-related anxieties: During past Thanksgivings, she would eat first with her mother, father and brother, then head to her boyfriend’s house for a second meal, where she would eat until she felt incapable of moving. Guilt and shame soon set in, and she would text her mother, who would write back saying she got it, that she was there for her daughter.

“The compulsive nature of it, the free rein to just eat a bunch of crap, is what has changed,” Regina said.

This year, Maeve said she and her mother will be able to enjoy the day at home in Old Saybrook, Conn., instead of dreading its aftermath.

“I’m actually excited about spending time with my parents and my brother and then my boyfriend’s family without that just major amount of anxiety that I usually have regarding food,” Maeve said. “I think it’ll definitely be a new experience. And having my mom to do it with me is going to be really nice.”

The holiday highlights family members’ eating habits, said Adrienne Bitar, a lecturer in American Studies at Cornell and the author of a book on diet culture. Any deviation from the standard menu — whether because of Ozempic, a food allergy or veganism — can attract outsize attention. Family members may offer unwanted observations on a person’s body, or moral judgments about using the drugs to lose weight.

“I’d be hard-pressed to find another occasion in which someone’s eating habits are so on display in a setting that is often marked by a lot of family tension and fraught family dynamics,” Dr. Bitar said.

She also thinks the drugs may change how people respond to questions about their eating. “Instead of saying, ‘Hey, Uncle Bob, butt out,’” she said, someone who has been prescribed Ozempic by a doctor might respond along the lines of: “This is a medical decision not up for debate between you and me at the Thanksgiving table.”

Alexa Rimmer, 29, remembers how self-conscious she felt last Thanksgiving. She had been taking Mounjaro for two months and was nervous about whether her mother and grandmother would comment on how little she was eating — a single slice of turkey, a spoonful of mashed potatoes, a sliver of pumpkin pie.

“My mom would always do the stereotypical, ‘This is the day to go all out, don’t feel guilty’ — that type of thing where you’re feeling the pressure to be eating a lot with your family. That’s the event everyone’s participating in to bond,” she said.

She was pleasantly surprised when no one commented on her portions. She had decided not to tell anyone in her family that she was on the medication, afraid they would view it like an eating disorder. “I was really worried that it would open up a conversation about like, ‘Oh, is this a problem, are you uncomfortable with yourself?’” she said.

Weeks later, when she was back home in Jupiter, Fla., for Christmas, her mother pulled her aside to ask if she was on a weight-loss drug. Alexa told her. Her mother had a confession, too: She was on Ozempic.