FDA APPROVES WEGOVY (SEMAGLUTIDE) FOR MASH (FATTY LIVER DISEASE)
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.
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.
ORAL WEGOVY (SEMAGLUTIDE) COMING SOON
In May 2025, Novo Nordisk applied for FDA approval of an oral version of semaglutide (Wegovy). In a 64-week trial enrolling 307 overweight adults, oral semaglutide 25 mg once daily caused 13.6% weight loss compared to 2.2% with placebo. Common side effects in the semaglutide group included nausea (47%), vomiting (31%), and constipation (20%). The FDA anticipates a decision on approval in the fourth quarter of 2025. If approved, this medication will become the first oral GLP-1 receptor agonist approved for weight loss. Eli Lilly is also developing an oral GLP-1 therapy called Orforglipron, which caused 12.4% weight loss over 72 weeks in a study enrolling 3,127 overweight adults.
This is a significant development, particularly in terms of cost. Oral medications are generally less expensive to manufacture than injectable ones, so it's likely the oral formulations will cost less than the injections. Wegovy and Zepbound, which initially cost around $1000, are now available for half that due to competition between the drugs. As more GLP-1 options become available, prices should continue to decline.
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.
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.
