GLP-1 pills for weight loss: The race is on

Drugmakers Novo Nordisk and Eli Lilly and Company have transformed the landscape of chronic weight loss management with the glucagon-like peptide-1 (GLP-1) drugs. GLP-1s are incretin mimetics that, as the name suggests, imitate the action of the incretin hormone GLP-1 and, consequently, slow gastric emptying, stimulate insulin release, and decrease glucose production by the liver while increasing its uptake by the muscles. Initially developed to treat type 2 diabetes, GLP-1s’ claim to fame lies in their ability to promote and maintain significant weight loss.

Available as a pill

Until recently, all the GLP-1 drugs approved by the FDA for weight management in patients with obesity or overweight have been formulated as subcutaneous injections that require temperature-sensitive storage and transportation. The self-administered injections are intended to be injected into the fatty tissue just under the skin. The recommended injection sites are the front of the thigh, the lower abdomen and the upper arm. The unprecedented popularity of the GLP-1s shows that the delivery route has not been a significant obstacle.

Even so, a pill form might create even more demand for GLP-1s for weight loss. In December 2025, the FDA approved an oral version of Novo Nordisk’s Wegovy (semaglutide) for chronic weight management in adults with obesity or overweight with a weight-related condition. The drug is also approved to reduce the risk of major adverse cardiovascular events in adults with obesity or overweight and cardiovascular disease. It became available in the US in early January 2026.

The Wegovy pill isn’t the first oral GLP-1. The FDA approved Novo Nordisk’s Rybelsus, a pill form of semaglutide, back in 2019. But Rybelsus is approved as a treatment for Type 2 diabetes, not weight loss. Rybelsus comes in a starter 3-milligram (mg) dose and 2 others: 7 mg and 14 mg. The Wegovy pills come in a starter 1.5-mg dose, two intermediate doses of 4 mg and 9 mg, and then a 25-mg dose.

Oral Wegovy offers an alternative to weekly injections in a convenient tablet formulation that is easier to store and distribute. GLP-1 injections must be stored and transported under refrigeration. The Wegovy tablets may be kept at room temperature. For the needle averse, the new product offers an oral option with once-daily dosing.

The Wegovy pills come with specific food and liquid restrictions. They must be taken in the morning on an empty stomach with up to 4 ounces of water only. The patient must wait at least 30 minutes before consuming any food, drink or other oral medications.

In clinical trials, patients who took Wegovy tablets achieved an average 13.6% weight loss, with 79% of patients experiencing at least a 5% weight loss. Common side effects included nausea, diarrhea, vomiting, constipation and abdominal pain.

The wholesale acquisition cost for all doses of Wegovy tablets is $1,349.02 for a 30-day supply, the same as for a 4-week supply of the injections. In February, Novo Nordisk, a Danish company, announced it would cut the list prices of its semaglutide products in half next year as competition among GLP-1s heats up.

Currently, self-paying patients may be able to buy a one-month supply of Wegovy 1.5-mg or 4-mg tablets for $149 through the manufacturer’s direct-to-consumer NovoCare program. But that lower price is available only for new patients, and fine print on the website in late February said the discounted $149 price for the 4-mg pill would only last until April 15, 2026, when it would go up to $199. The $149 price for the 1.5-mg pill, which is not discounted, will stay the same.

Novo Nordisk currently enjoys a full share of the oral GLP-1 weight loss market, but two other agents in the pipeline may soon trigger some fierce competition.

Foundayo approved

Foundayo (orforglipron) is an oral GLP-1 receptor agonist developed by Eli Lilly for the treatment of obesity, overweight and type 2 diabetes. It differs from the Wegovy tablet in that it is a small nonpeptide molecule designed to be easier to manufacture and more readily absorbed by the body. In contrast, semaglutide, the active ingredient in Wegovy tablets, is a large peptide molecule that requires morning dosing with food and liquid restrictions for optimal absorption. In clinical trials, Foundayo was taken at any time of the day without regard to meals or liquids.

The ATTAIN-1 study was a phase 3 multinational, double-blind trial in which 3,127 participants were randomly assigned to receive once-daily doses of Foundayo 6-, 12-, or 36-mg capsules or placebo. The study evaluated the safety and efficacy of orforglipron in adults with obesity without diabetes. The primary end point was the percentage change in body weight after 72 weeks. Secondary end points included the percentage of participants who had a body weight reduction of at least 5%, 10%, 15% or 20%.

Patients who received Foundayo were started at a dose of 1 mg and titrated up every four weeks until they reached their assigned dose. Each participant received counseling on eating a balanced diet and physical activity.

At 72 weeks, patients taking the 6-mg dose of the study drug lost a mean of 7.5% of their body weight, those taking the 12-mg dose lost a mean of 8.4% and patients in the 36-mg group lost a mean of 11.2%. In comparison, participants taking a placebo lost an average of 2.1% of their body weight. Additionally, a significantly greater percentage of participants who received any dose of Foundayo achieved at least a 5% decrease in body weight. Of those taking the dose (36 mg), 71.8% experienced weight loss of at least 5% compared with 26.8% in the placebo group.

Common side effects were mild to moderate and primarily gastrointestinal. The most frequent resembled those experienced with GLP-1s administered subcutaneously and included nausea, constipation, diarrhea, vomiting and dyspepsia. Five cases of mild pancreatitis were reported in the Foundayo groups, with no cases of medullary thyroid cancer noted. It is not talked about much, but all the FDA-approved GLP-1s have boxed warnings for the potential risk of medullary thyroid cancer.

The FDA announced that it had approved Foundayo on April 1. Foundayo was studied as a capsule in the ATTAIN clinical program, but the FDA approved it as a tablet at dose-equivalent formulations (e.g., the FDA-approved 17.2-mg tablet is the dose equivalent of the 36-mg capsule assessed in clinical trials).

VK2735

Eli Lilly and Novo Nordisk are major pharmaceutical companies, but some smaller companies are also entering the oral GLP-1 arena. San Diego-based Viking Therapeutics completed the phase 2 VENTURE-Oral Dosing trial evaluating the tolerability, safety, pharmacokinetics and weight loss efficacy of VK2735. The investigational agent is a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist being developed as subcutaneous injection and oral forms. GIP is an incretin hormone that promotes insulin release in response to meals. GIP receptor activation has been used to enhance the therapeutic effects of GLP-1 agonists. Tirzepatide, marketed by Eli Lilly as Mounjaro for diabetes and Zepbound for weight loss, is currently the only FDA-approved dual GLP-1/GIP receptor agonist. Viking Therapeutics is developing an oral version.

The VENTURE-Oral Dosing trial tested the oral form of VK2735 on adults with obesity or overweight with at least one weight-related condition. Participants were randomly assigned to receive a placebo or a once-daily oral dose of VK2735 at 30, 60, 90, or 120 mg. All doses greater than 15 mg achieved a statistically significant decrease in body weight after 13 weeks, with patients taking 120 mg experiencing a mean 12.2% decrease in body weight, compared with 1.3% for those taking placebo. Additionally, up to 97% of patients in the VK2735 groups achieved a weight loss of at least 5% compared with 10% of those in the placebo group.Following these encouraging results, the company plans to begin phase 3 studies in the third quarter of 2026.

GLP-1s in comparison

As more oral GLP-1 agonists enter the market, they are predicted to capture over one-third of the GLP-1 weight management market. Although individual trials do not show that tablets are superior to injections for promoting weight loss, some patients may gravitate toward oral GLP-1s simply because of their ease of use and storage. This may be especially true given the similarities in side effect profiles.

For now, oral GLP-1 agonists do not surpass their injectable counterparts in weight-loss efficacy. But VK2735 could be a contender if it performs as well as Zepbound in phase 3 trials