Do Oral GLP-1 Drugs Work as Well as Injectables? We Checked the Science

For the millions of people using glucagon-like peptide-1 receptor agonists (GLP-1), a dose has long meant a weekly appointment with a needle. With the U.S. Food and Drug Administration (FDA) approving semaglutide (Wegovy) pills for weight management, a pill option is now available — with more approvals potentially to come.

Until recently, the stomach was a “dead zone” for GLP-1s because stomach acid and digestive enzymes break down peptides before the body can absorb all of them. New oral GLP-1s are designed to protect peptides, the active ingredients in these medications, so they can survive the trip through your digestive tract.

Why does it take a 25 mg daily pill to do the same job as a 2.4 mg weekly injection? The higher dose ensures enough of the drug survives the trip through your system to be effective. The actual effect of the medication is nearly the same.

“The absorption of the oral med from the [gastrointestinal] tract into the bloodstream is poor, such that the amount of medication entering the bloodstream is similar for the oral and injectable,”  says W. Timothy Garvey, MD, a professor of medicine at the University of Alabama at Birmingham.

“The pill contains the same medicine as the injectable, and it’s highly likely that the health benefits will be the same,” Dr. Garvey says.

And the benefits aren't just physical — they're mental, too. Because the pill mimics natural hormone functions, it travels to the brain to target the reward centers that drive overeating, says Sara Velayati, MD, an obesity medicine specialist at the Fleischer Institute Medical Weight Center at Montefiore Einstein in New York. This process helps quiet food noise, constant, intrusive thoughts about your next meal that can make weight management difficult.

The biggest difference between GLP-1 shots and pills is your routine for taking the medication.

• Injection You inject the medication under the skin once a week. You can take it with or without food, but you must keep the medicine refrigerated.

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• Pill You must take the pill daily, on an empty stomach, with 4 ounces of water or less. You must then wait at least 30 minutes before eating or drinking anything else, including other medications. If you don't wait, your body might not digest enough of the medicine.

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“In my experience, waiting 30 minutes to eat does not present an undue burden on patients, who adjust to this just fine,” Garvey says.

Although Wegovy is the first GLP-1 pill the FDA has approved for weight management, drug manufacturers are funding trials for additional oral GLP-1 medications.

• orforglipron This small-molecule drug likely won't require the strict 30-minute fasting rule because the stomach does not break it down as easily. At its highest dose, 36 mg, participants in a phase 3 trial lost an average of 12.4 percent of their starting weight over 72 weeks.

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   The manufacturer, Eli Lilly Co., has submitted orforglipron to the FDA for approval for use in weight management, with a decision expected in the second quarter of 2026.

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• aleniglipron Structure Therapeutics is testing this small-molecule oral GLP-1. Participants in its phase 2b trial lost an average of 14.2 percent of their body weight over 36 weeks using a daily 240 mg dose, the company says.

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• amycretin Novo Nordisk, which makes Wegovy and Ozempic, is testing this experimental, unimolecular drug to target two hormone pathways, GLP-1 and amylin, a hormone that helps control hunger. The mean weight loss among participants in its phase 1 trial was 13 percent of their starting body weight after 12 weeks.

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• People who take oral GLP-1 medications for weight management have lost about the same amount of weight as those using injectable medications, according to research that the U.S. Food and Drug Administration used for approving the drugs.
• Oral and injectable GLP-1s offer benefits beyond weight loss and may help you manage blood sugar, blood pressure, and cholesterol levels.
• Side effects for GLP-1 pills and injectables are similar, mostly involving gastrointestinal issues, especially when you start taking medication for the first time.
• The primary difference between the medication types is that you must take semaglutide pills daily, with food and beverage restrictions, while semaglutide injections are administered weekly.
• Trials are underway for additional GLP-1 pills that may have fewer dietary restrictions.