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WEGOVY PILL RECEIVES FDA APPROVAL
December 2025

On December 22, 2025, Novo Nordisk announced that its oral semaglutide pill, to be named Wegovy, like the injection, was FDA-approved for weight loss. In a 64-week trial enrolling 307 overweight adults, oral semaglutide 25 mg once daily caused an average weight loss of 13.6% compared to 2.2% with placebo. The subgroup of patients who adhered perfectly to the semaglutide treatment regimen (i.e., did not discontinue the drug) lost an average of 16.6%. The drug was titrated in the following manner:

• 3 mg once daily for 4 weeks
• 7 mg once daily for 4 weeks
• 14 mg once daily for 4 weeks
• 25 mg once daily thereafter

Novo Nordisk says oral Wegovy will be available in early January, with starting doses costing $149 per month. The pill must be taken in the morning on an empty stomach, 30 minutes before eating, drinking, or using any other oral medication.

This is great news for the affordability of GLP weight-loss therapies. Eli Lilly also has an oral GLP coming soon that will compete with Wegovy, further driving down pricing on these medications and the injections.

• Novo Nordisk press release

NEXT-GENERATION GLP THERAPY CAUSES REMARKABLE WEIGHT LOSS IN STUDY
December 2025

Current GLP therapies target one or two hormone receptors; Wegovy (semaglutide) targets GLP-1, while Zepbound (tirzepatide) targets GLP-1 and GIP. Eli Lilly is developing a next-generation GLP therapy called retatrutide that targets three receptors: GLP-1, GIP, and glucagon.

Eli Lilly recently published preliminary results from a 68-week retatrutide study, where 445 overweight adults (average BMI 40; average body weight 249 lbs) were randomized to once-weekly injections of retatrutide 9 mg, retatrutide 12 mg, or placebo. After 68 weeks, average weight loss in the retatrutide 12 mg group was a remarkable 28.7%, equating to an average weight loss of 71 lbs. The retatrutide 9 mg group lost an average of 26.4%, and the placebo group lost 2.1%. The most common side effects with the 12 mg dose were nausea (43.2%), diarrhea (33.1%), constipation (25.0%), and vomiting (20.9%). In the 12 mg group, 18.2% of patients discontinued treatment due to adverse events; however, some discontinuations were actually due to "perceived excessive weight loss," highlighting the potency of the drug.

The most effective therapy available now is Zepbound, which causes about 20% weight loss. Retatrutide's near 30% weight loss is remarkable and rivals what is typically seen with bariatric surgery.

• Eli Lilly retatrutide press release

HIGH-DOSE WEGOVY MAY BE COMING SOON
December 2025

Wegovy (semaglutide) is currently approved for chronic weight management at a maximum weekly dose of 2.4 mg. Studies have shown this dose causes average weight loss of 13% to 16%, an effect that is less than the 20% to 22% seen with its primary competitor, Zepbound (tirzepatide). To evaluate whether a higher dose of Wegovy is more effective, researchers performed the STEP UP trial, where 1407 obese adults were randomized to Wegovy 7.2 mg, Wegovy 2.4 mg, or Placebo. Over 72 weeks, mean weight loss was 18.7% in the Wegovy 7.2 mg group, 15.6% in the Wegovy 2.4 mg group, and 3.9% in the placebo group (p<0.0001). Gastrointestinal side effects were more common in the 7.2 mg group compared to the 2.4 mg group (70.8% vs 61.2%). Dysaesthesia, an unpleasant and often painful sensation, such as burning or tingling under the skin, was also more common in the 7.2 mg group (22.9% vs 6.0%).

Novo Nordisk has submitted a supplemental New Drug Application to the FDA for the 7.2 mg dose. The company hopes to receive an expedited review period of one to two months, potentially making the high-dose option available in early 2026.

• Wegovy 7.2 mg for Weight Loss, Lancet Diabetes Endocrinol (2025)

WEGOVY PRICE DROPS TO $349 PER MONTH
November 2025

Effective November 17, 2025, Novo Nordisk has significantly reduced the price of its popular weight-loss drug, Wegovy.

• Standard Purchase: The new price is $349 per month when ordered through the company's mail-order pharmacy, NovoCare Pharmacy.


• Limited-Time Offer: New patients can receive the initial two doses (0.25 mg and 0.5 mg) for only $199 per month between November 17, 2025, and March 31, 2026.

This move marks the latest drop in a striking pricing trend. Since its launch in 2021, the cost has fallen from over $1,000 a month to $650, $499, and is now $349. This remarkable affordability is a direct result of aggressive competition, primarily from Eli Lilly's Zepbound. Indeed, competition is proving to be a beautiful thing for patient affordability.

• Wegovy website

NON-GLP WEIGHT-LOSS INJECTION IMPRESSES IN TRIAL
November 2025

Eli Lilly reported impressive results for an experimental once-weekly weight-loss injection called eloralintide that is not part of the GLP class. Eloralintide mimics the actions of amylin, a hormone that slows gastric emptying and suppresses hunger. While these actions are similar to those of GLP-1 analogs like Wegovy and Zepbound, there is some evidence that, compared to GLP-1 drugs, amylin analogs are better tolerated and help preserve lean muscle mass. In a 48-week study enrolling 263 overweight adults, patients receiving the lowest dose of eloralintide lost 9.5% of their body weight, while those on the highest dose lost 20%. Lilly plans to start conducting larger trials with the drug soon.

• Lilly press release on eloralintide

FDA APPROVES GENERIC VERSION OF SAXENDA
August 2025

In 2014, Saxenda (liraglutide) became the first GLP drug approved for weight loss. It causes average weight loss of about 8%, much less than what is seen with Wegovy (16%) and Zepbound (22%); therefore, it did not receive as much fanfare as the latter two. It is also injected daily as opposed to weekly, making it less attractive to some patients.

The FDA recently approved the first generic version of Saxenda. Generic drug prices are initially high because only one manufacturer is allowed to produce the drug for six months. After that, other manufacturers enter the market, and prices typically come down. In six to twelve months, generic Saxenda will likely be another affordable weight-loss medication. Additionally, it is one of three drugs approved to treat obesity in adolescents 12 years and older, with Qsymia and Wegovy being the other two.

• Teva Pharmaceuticals Press Release on Generic Saxenda Approval
• Saxenda review

FDA APPROVES WEGOVY (SEMAGLUTIDE) FOR MASH (FATTY LIVER DISEASE)
August 2025

Metabolic dysfunction–associated steatohepatitis (MASH), also known as fatty liver disease, is a condition strongly associated with obesity that causes chronic liver inflammation and scarring. The ESSENCE study, published in 2025, found that Wegovy-induced weight loss significantly improved MASH pathology compared to placebo. In August 2025, the FDA approved Wegovy for MASH based on ESSENCE's findings.

MASH is a common condition, affecting an estimated 25% of American adults and up to 90% of people with a BMI of 40 or greater. There is only one other FDA-approved treatment for MASH, a drug called Rezdiffra that stimulates thyroid receptors in the liver but does not cause weight loss. The questions now are when will insurance companies start covering Wegovy for MASH and what the requirements will be. Prior authorization criteria for Rezdiffra vary by insurance, but I know some plans require the following: (1) MASH diagnosis by liver biopsy, Fibroscan, or magnetic resonance elastography (MRE), (2) prescribed by a gastroenterologist or hepatologist. If insurance companies use the same criteria for Wegovy, it will create a significant barrier to access, especially through primary care.

• FDA news release on Wegovy approval for MASH
• ESSENCE Study abstract

ORFORGLIPRON: A NEW ORAL GLP-1 THERAPY COMING SOON

Eli Lilly plans to file for FDA approval of their oral GLP-1 agonist orforglipron by the end of 2025. In a 72-week study enrolling 3,172 overweight adults, the highest dose of orforglipron (36 mg) caused 12.4% weight loss. If orforglipron is approved along with Novo Nordisk's oral Wegovy (see Oral Wegovy), there will be two oral GLP-1 therapies available in 2026.

This is a significant development regarding cost because pills are much cheaper to manufacture than injections. Additionally, having two pills competing against each other will also likely lower prices. Competition between injectable therapies Wegovy and Zepbound has brought prices down from over $1,000 a month when they were first introduced to $499 a month currently.

• Eli Lilly Orforglipron press release

SECRET WEIGHT-LOSS WEAPON: THE FOOD SCALE

When patients ask me what they can do to enhance their weight loss, the first question I ask them is whether they weigh their food. While it may seem silly to weigh out everything you are about to eat, studies have shown that people who weigh their food eat less. Reasons weighing food helps with weight loss include:

• Accurate Portion Control: This is the most significant benefit. Our perception of "a serving" or "a handful" can be vastly different from actual serving sizes. Weighing food takes the guesswork out of portion control, ensuring you're consuming the precise amount you intend. This is crucial because even healthy foods, when eaten in excess, can lead to weight gain.
• Precise Calorie and Macro Tracking: If you're tracking calories or macronutrients (protein, carbs, fats), weighing your food is the most accurate way to do so. Nutritional information on labels is typically given for a specific weight (often in grams). Without a scale, it's easy to underestimate your intake, which can derail your progress.
• Increased Awareness and Mindfulness: The act of weighing food forces you to be more mindful of what and how much you're eating. This increased awareness can help you identify patterns of overeating, understand the energy density of different foods, and make more informed choices.

CANCER STUDY SHOWS PROFOUND EFFECT OF EXERCISE

The benefits of exercise on a wide range of conditions, including everything from ADHD to osteoporosis, have long been known. Now, a randomized controlled trial published in the New England Journal of Medicine has found that exercise improves survival in patients with colorectal cancer. The CHALLENGE study randomized 889 patients with resected colon cancer (stage III or high-risk stage II) who had completed adjuvant chemotherapy to a structured exercise program with required visits over 3 years (exercise group) or general health-education materials (control group). After a median follow-up of 7.9 years, the primary endpoint, 5-year disease-free survival, was 80.3% in the exercise group and 73.9% in the control group (difference, 6.4 percentage points; 95% CI 0.6 to 12.2). Eight-year overall survival was 90.3% and 83.2%, respectively. Notably, weight loss did not differ significantly between groups, so it does not explain the observed effect.

Exercise improved overall survival among colorectal cancer patients by 7%. The study authors note that this effect size is similar to what is observed with many approved drug therapies, minus the side effects and costs. This study provides yet another reason for people to exercise.

• Structured Exercise after Adjuvant Chemotherapy for Colon Cancer, NEJM (2025)

OPTIONS AFTER ACHIEVING WEIGHT-LOSS GOAL ON GLP DRUGS

A question I'm often asked is how semaglutide (Wegovy) and tirzepatide (Zepbound) are managed after someone reaches their weight-loss goal. There is no one-size-fits-all answer, as it mostly depends on the individual and their ability to maintain good eating habits. The three main options are discussed below.

• Stay on the medication at the same or a reduced dose: There is no limit on the duration of GLP therapy. The first GLP analog, Byetta, was approved in 2005, and since then, many diabetics have used these medications for life. Some patients may choose to lower their dose to see if they can maintain their weight at a reduced strength.


• Stop or taper off the medication: GLP analogs may be stopped abruptly without adverse withdrawal symptoms. Alternatively, they may be tapered off over a period of time. Once the medication is discontinued, its effects on appetite dissipate over several weeks. Weight regain after stopping depends on the individual's ability to maintain their eating habits. Several studies have evaluated weight regain after stopping GLP drugs. In one, patients who lost 10.6% of their weight after 20 weeks of Wegovy were randomized to continue it or switch to placebo. Over the next 48 weeks, patients who received placebo regained 7% of their weight, while those who continued Wegovy lost an additional 8%. [Study abstract] In another, patients who lost 21% of their weight after 36 weeks of Zepbound were randomized to continue it or switch to placebo. Over the next year, the placebo group regained 14% of their weight, while the Zepbound group lost an additional 5.5%. [Study abstract]


• Increase the interval between doses: Another option is to increase the interval between doses to greater than one week. No studies have evaluated this practice, so I cannot speak to its effects in a controlled setting. Anecdotally, I can say this has worked for some of my patients.