Semaglutide: Pill vs. Injection—Which Works Best for Weight Loss?

In March 2025, the European Medicines Agency (EMA) sounded the alarm: semaglutide, the blockbuster drug behind weight loss and diabetes management, is facing a prolonged shortage. Fueled by skyrocketing demand—thanks to social media buzz and celebrity endorsements from figures like Elon Musk—pharmaceutical giant Novo Nordisk is struggling to keep up. Known for its brand names Ozempic and Wegovy, semaglutide has become a household name, not just for treating type 2 diabetes but for its remarkable ability to help people shed pounds. Now, with an oral tablet form gaining traction alongside the traditional injectable version, patients and doctors face a new question: which is better? This article dives into the differences between oral and injectable semaglutide, their effectiveness for weight loss, how to use them, and what science says about this game-changing drug.

The Semaglutide Surge: Why It’s Making Headlines

Semaglutide belongs to a class of drugs called GLP-1 receptor agonists, originally developed to manage type 2 diabetes. Its unexpected superpower? Helping people lose significant weight by curbing appetite and slowing digestion. The drug’s popularity exploded as influencers and celebrities shared dramatic weight loss stories, creating a frenzy that has strained global supplies. The EMA’s warning underscores the challenge: as more people seek semaglutide for weight loss, access is becoming a hurdle. Meanwhile, the introduction of an oral tablet has sparked curiosity about whether it can match the injectable version’s results without the needle.

Oral vs. Injectable: How Do They Compare?

At first glance, the choice between a daily pill and a weekly shot seems like a matter of convenience. But there’s more to it. Both forms of semaglutide work by mimicking GLP-1, a hormone that regulates blood sugar and appetite. They bind to GLP-1 receptors, boosting insulin release, reducing blood sugar spikes, and slowing digestion to make you feel fuller longer. They even act on the brain to dial down hunger. So, how do the two delivery methods stack up?

• Oral Semaglutide: Taken once daily, the tablet is a game-changer for those who dread needles. It’s swallowed with a small sip of water (about half a cup) on an empty stomach, ideally first thing in the morning. You must wait at least 30 minutes before eating, drinking, or taking other medications. Unlike the injectable version, the tablet doesn’t require refrigeration, making it easier to store and travel with. However, the pill’s absorption can be finicky—food or other drugs in your stomach can reduce its effectiveness.
• Injectable Semaglutide: Administered once a week via a subcutaneous shot (think belly, thigh, or upper arm), the injection delivers a steady dose. It requires cold-chain storage, meaning it must be kept refrigerated until use, which can be a hassle for some. The needle may intimidate, but the weekly schedule is less demanding than a daily pill.

In terms of effectiveness, science suggests the two are neck-and-neck when used correctly. A review published in Diabetes Therapy found that oral semaglutide lowers HbA1c (a key marker of blood sugar control) as effectively as the injectable version, sometimes even outperforming it when paired with insulin for type 2 diabetes. For weight loss, the oral form holds its own, showing slightly better results than some other GLP-1 drugs, though it doesn’t significantly outshine the 1 mg injectable dose of semaglutide.

Weight Loss: What the Numbers Say

Semaglutide’s weight loss potential is where it truly shines, and the data is striking. In the STEP 1 trial, published in The New England Journal of Medicine in 2021, researchers tested semaglutide in 1,961 overweight or obese adults without diabetes. Participants were split into two groups: one received weekly 2.4 mg injections of semaglutide, while the other got a placebo. Both groups followed lifestyle changes, like diet and exercise, for 68 weeks.

The results were jaw-dropping. The semaglutide group lost an average of 14.9% of their body weight—about 30 pounds for a 200-pound person—compared to just 2.4% in the placebo group. Even more impressive, 86.4% of the semaglutide group shed at least 5% of their weight, 69.1% lost 10% or more, and 50.5% dropped 15% or more. In contrast, only 31.5%, 12%, and 4.9% of the placebo group hit those milestones. These numbers highlight why semaglutide has become a go-to for weight management.

While the STEP 1 trial focused on injectable semaglutide, studies on the oral form suggest comparable weight loss when doses are equivalent. The catch? Sticking to the oral version’s strict dosing rules is critical to getting the full effect.

How to Take Semaglutide Correctly

Whether you choose the pill or the shot, proper use is key to success. Here’s how to get it right:

• Oral Semaglutide:
  1. Take one tablet daily, first thing in the morning, on an empty stomach.
  2. Swallow it whole with no more than 4 ounces (120 mL) of water—don’t crush, chew, or split it.
  3. Wait at least 30 minutes before eating, drinking, or taking other medications.
  4. If you miss a dose, skip it and take the next one the following day.
• Injectable Semaglutide:
  1. Inject once weekly, on the same day each week, in the abdomen, thigh, or upper arm.
  2. Store in the fridge and keep it cold until use.
  3. Follow your doctor’s instructions for rotating injection sites to avoid irritation.

Side Effects: What to Watch For

Like any medication, semaglutide comes with potential side effects, mostly tied to the digestive system. Common complaints include nausea, bloating, constipation, or diarrhea. These often fade as your body adjusts, but they can be bothersome. In rare cases, severe abdominal pain with vomiting could signal a serious issue like pancreatitis. If this happens, stop the drug and seek medical help immediately.

Expert Insights: What Doctors Say

Dr. Sarah Johnson, an endocrinologist at Johns Hopkins Medicine, emphasizes that semaglutide isn’t a magic bullet. “It’s incredibly effective, but it works best with lifestyle changes—healthy eating, regular exercise, and good sleep,” she says. “The oral version is a fantastic option for needle-averse patients, but discipline with dosing is non-negotiable.” She also warns against off-label use without medical supervision, especially given the drug’s shortage.

On the weight loss front, Dr. Michael Chen, a bariatric specialist, notes that semaglutide’s ability to reset appetite makes it a powerful tool. “It’s not just about eating less; it rewires how your brain responds to food cues,” he explains. However, he cautions that weight can creep back if the drug is stopped without a maintenance plan.

Looking Ahead: Access and Advice

With semaglutide in short supply, patients may face delays or tough choices between oral and injectable forms. If you’re considering semaglutide, talk to your doctor to weigh the pros and cons based on your health, lifestyle, and preferences. For weight loss, pair the drug with sustainable habits—think balanced meals and regular movement—to maximize results and keep the weight off long-term.

For those wary of side effects or access issues, stay informed. Check with your pharmacy about availability, and don’t fall for unregulated online sellers peddling knockoffs. As research continues, newer GLP-1 drugs or improved formulations may ease shortages and expand options.

Semaglutide, whether swallowed or injected, is reshaping the fight against obesity and diabetes. Its science-backed results are undeniable, but it’s not a one-size-fits-all fix. With the right approach, it could be a life-changing step toward better health.

This article draws on research from The New England Journal of Medicine (2021) and Diabetes Therapy (2024), with insights from Dr. Sarah Johnson and Dr. Michael Chen.