Shake it up: New oral weight loss drug

On Nov. 6, 1981, the Cars released their 4th studio album titled "Shake It Up." Ric Ocasek was the lead vocal and guitarist for the new wave band. He wrote the majority of their hits including the single titled as the album. The single Shake It Up reached number 4 on the Billboard Hot 100 charts in the United States. One of the lyrics in the song is "Shake it up, make a scene." One could say the GLP-1 (glucagon-like peptide-1) weight loss drugs did shake it up and make a scene in 2025. Approximately 12% of the U.S. adult population is taking a GLP-1 drug for weight loss based on 2 different surveys. The GLP-1 drugs were first FDA-approved for treating type 2 diabetes. In April of 2005, the FDA approved exenatide (Byetta) daily injection as the first GLP-1 drug to manage diabetes. Seven different GLP-1 drugs have been approved and marketed in the U.S. for diabetes, while only 3 GLP-1 drugs have been approved for weight loss. Two of the three have GLP-1 as their sole mechanism of action. This includes liraglutide (Saxenda) and semaglutide (Wegovy). Liraglutide is a daily injection for weight loss, while semaglutide is a weekly injection. Tirzepatide (Zepbound) works by a dual mechanism of action including GLP-1 with additional benefit from a GIP (glucose-dependent insulinotropic polypeptide) action. The generic names are the same for both diabetes and weight loss, but given different brand names. For example, semaglutide is known as Wegovy for weight loss and Ozempic for diabetes and tirzepatide is Zepbound for weight loss and Mounjaro for diabetes. Similarly, liraglutide is Saxenda for weight loss and Victozia for diabetes. All 3 of the GLP-1 drugs for weight loss were only available in an injectable form until the FDA approved the oral Wegovy on December 22, 2025. The oral tablet is also generically known as semaglutide. An oral semaglutide tablet by the brand Rybelsus had been approved in the U.S. for managing diabetes. Rybelsus tablets are available as 3 mg, 7 mg, and 14 mg. However, the new Wegovy tablet for weight loss comes as 1.5 mg, 4 mg, 9 mg, and 25 mg. One might wonder why all the Wegovy tablet strengths. Just like the stairstep dosing with the GLP-1 injectable drugs, the tablets follow a similar pattern. The FDA-approved dosing for the oral Wegovy is 4 weeks of the 1.5mg daily, then 4 weeks of 4mg daily followed by 9mg tablets daily for 4 weeks until the maximum strength of 25mg daily is achieved. The maintenance dose for weight loss would be 25mg daily. The FDA-approved labeling for oral Wegovy is for chronic weight management in conjunction with a reduced calorie diet and physical activity. The oral Wegovy was given approval for reducing the risk of heart disease. The New England Journal of Medicine published the clinical study confirming these findings on September 17, 2025. The study was known as OASIS 4 and showed a mean weight loss of 16.6% over 64 weeks. Not all GLP-1 medications are created equal. The NEJM published a comparator study of semaglutide injection to tirzepatide injection for weight loss. The SURMOUNT-5 trial showed an average weight loss of 20.2% for tirzepatide compared to 13.7% for semaglutide. This may be contributed to tirzepatide's dual mechanism of action. Other studies of weight loss with semaglutide have shown a higher loss than the 13.7%. These drugs are not without side effects. A study published in the Annals of Internal Medicine evaluated emergency room visits for patients taking semaglutide for weight loss. The study found 4 out of every 1,000 users needed evaluation for side effects. The vast majority were gastrointestinal including nausea, vomiting, and diarrhea. The most surprising aspect of the study was about 16% came to the ER with low blood sugar. This is unusual because the GLP-1s lower blood sugar in diabetes, but typically were not known for lowering blood sugar in those without diabetes. The oral Wegovy tablets are to be available in pharmacies by January. The GLP-1 weight loss drugs can be expensive and this cost can be a rate limiting step for some. Not all insurance covers these medications for weight loss, which compounds the expense to the consumer. Novo Nordisk, who manufacturers oral semaglutide products, does offer some introductory discounts through the company's website. The problem is these drugs are meant for more long-term use and the discounts will only last for a short period of time. The new oral Wegovy may shake it up in 2026! Karen Kier is a pharmacist with the ONU HealthWise team.