Wegovy vs Wegovy

This is a guest post from David White, a nurse practitioner and author of The Incretin Space, where he dives into recent GLP-1 research in even greater depth. If you enjoy exploring the science behind these breakthroughs, I highly recommend checking it out.

Oral Wegovy has arrived and it's a big shift for obesity medicine.

The innovation lies in both the formulation and accessibility. Novo Nordisk has engineered a tablet version of semaglutide, using a proprietary technology called SNAC. This absorption enhancer allows the peptide to survive the harsh environment of the stomach and reach systemic circulation intact - a remarkable feat for a molecule that would typically be destroyed by digestive enzymes within minutes.

Perhaps equally significant is the pricing strategy. Starting doses are available at $199 per month for cash-paying patients, positioning oral Wegovy as a potentially more accessible option in a market where cost remains a substantial barrier to care.

The Two Questions Everyone Asks

If you're considering switching to Oral Wegovy, two questions naturally arise:

• Does oral semaglutide deliver comparable weight loss to the injectable version?

• Is this a better option if you are afraid of needles?

The short answer to those questions is mostly yes, but with some very important caveats. And for any patient looking to start a weight loss journey those caveats matter! Especially if you want to successfully lose weight. 

What Injectable Semaglutide Can Achieve: The STEP-1 Foundation

Let’s first review what injectable semaglutide, aka, injectable Wegovy is capable of doing. 

I’ll primarily use the STEP-1 trial for our injectable data and OASIS-4 for our oral data. 

In STEP-1 we saw two numbers for weight loss, the first was -14.9% weight loss for 68 weeks of treatment, this is the treatment estimand, which essentially captures the real-world effect, including rescue meds or discontinuation and reflects the broad capability of the drug. Meanwhile the efficacy estimand was -16.9% which reflects efficacy estimand defines the treatment effect under ideal, controlled trial conditions. This estimates the effect if everyone took the drug as assigned, ignoring discontinuations or rescue meds

The Oral Alternative: What OASIS-4 Study Reveals

So that’s the injectable weight loss, but what about the oral weight loss? 

Using the OASIS-4 data, weight loss was 13.6% for the treatment estimand over 64 weeks and 16.6% for efficacy estimand. So on first blush that is actually quite similar in terms of weight loss, which is expected, it’s the same drug overall. But how about side effects, any difference there? Graph below: 

The oral semaglutide group was similar 6.9% stopping from adverse events and 3.4% stopping due to GI side effects. Looking at side effects overall, they’re again pretty similar with two exceptions, slightly more vomiting on the oral medication, but significantly less diarrhea.

I’m not sure what to make of that, but it also brings me to my final point about side effects. The injectable trial had 1300 patients in the semaglutide arm, but the oral trial only had 205. There simply could be a skew in the data because the oral arm was much smaller. 

Broken down a little bit further looking at discontinuation rates we see in the injectable group, about 7% of patients stopped the trial due to adverse events, with 4.5% stopping due to gastrointestinal side effects specifically.

How Taking Each One Really Feels Day-to-Day

The final consideration between these two different ways to take semaglutide is just that, dosing frequency and how to actually dose.

The injectable is easy, once a week you use an autoinjector with a very small needle and inject into your abdomen or thigh.

The oral version is a bit more complicated. Novo recommends taking it after an 8 hour fast with a couple ounces of water only, then continuing to avoid any other food or beverage for at least 30 minutes after swallowing the pill. For any hypothyroid patients who take levothyroxine, this probably sounds very familiar as it’s basically the same way to take that medication. Extra food or liquid will alter and slow down absorption of the semaglutide and lead to loss of efficacy of the drug. 

Where does this quick review leave us? Well, both drugs offer a path to weight loss, however, and I write this as someone who prescribes GLP-1 medications, the oral medication requires a little more dedication from the patient. It is absolutely cheaper, with the first two starting doses costing $149 and $199 in the USA, with the max dose being $299 per month for cash paying patients. This compares to $349 per month for any dose of the injectable, though as of the time of writing this article, the two starting doses of injectable semaglutide were $199 for the first 2 months in an offer that expires in late March 2026. 

My Honest Take

My own personal opinion is that I will prescribe either option to patients, they both clearly work, though, and I admit I think the injectable version is probably more effective over the long term, just a shot once a week is much easier than a pill. 

Circling back to the dedication point, patients will have to be willing to make sure they take their pill and not eat for at least 30 minutes afterwards. While that sounds easy and reasonable, this will broadly be a test of how well prescribers and pharmacies can hammer home that point to patients. I know I've reinforced that point to my patients who’ve asked about it so far. Otherwise, you’ll just swallow a very expensive placebo, and when your goal is effective weight loss, no one wants the placebo. 

Scientific References for this article:

_{Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021;384(11):989‑1002. doi:10.1056/NEJMoa2032183. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183}

_{Wharton S, Rubino DM, Ito D, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS‑4). New England Journal of Medicine. 2025;393(11):1077‑1087. doi:10.1056/NEJMoa2500969. Article access via NEJM: https://www.nejm.org/doi/full/10.1056/NEJMoa2500969​}