Weight-Loss Pills vs. Injections: Which Would You Choose?

Imagine that your doctor tells you there are two medicines that could help you shed a substantial amount of weight. One requires you to swallow a tablet. The other requires you to stick yourself with a needle. For many Americans, the answer seems obvious: give me the pill! But weight-loss pills raise a surprisingly interesting question about how much our preference for one form of medicine over another is shaped by culture.

Americans Have a Preference for Pills:

Needles make an awful lot of people unhappy. Others simply don’t like the idea of injecting themselves.

My mother developed type 2 diabetes in her late 80s after taking prednisone to treat polymyalgia rheumatica. She hated sticking herself with a lancet to test a drop of blood for glucose levels. That was before CGMs (continuous glucose monitors). These devices are about the size of a half dollar and are worn on the back of the arm. They contain a tiny sensor that detects blood sugar levels automatically.

Most Americans are like my mother. Needles make them squeamish. Instead, we swallow pills for headaches, hypertension, cholesterol, allergies, infections and diabetes, to name just a few common conditions. We’ve been doing that for generations. But that preference may have as much to do with culture as convenience. The way people take medicine isn’t as universal as most Americans assume.

What Does Medicine Look Like to You?

A fascinating international study asked 4,435 adults in 21 countries and regions how they preferred to receive medicine (Exploratory Research in Clinical and Social Pharmacy, Nov. 26, 2023). They were not restricted to pills and injections. Researchers asked about medicine swallowed by mouth, dissolved under the tongue, sprayed into the nose, inhaled into the lungs, applied to the skin, injected with a needle and administered rectally or vaginally.

Here is how the authors introduce their research:

“Medicines are most often taken by the oral route of administration,¹ and it is commonly believed that most people prefer to take medicines this way. It is also commonly assumed that most people would prefer to avoid the injection route if they had a choice. There is however, evidence that in some countries, injections are preferred over other routes of administration. The rectal route is unthinkable in some countries, somewhat better accepted in others and well accepted in a few countries for certain age groups or indications, e.g. paracetamol [acetaminophen] suppositories for infants.”

The researchers discovered a surprisingly strong connection between culture and people’s preferences. Oral medicine won overall, but by very different margins.

An extraordinary 98% of respondents classified as belonging to Protestant European culture selected oral medicine. Roughly 78% did so in the English-speaking cultural group that included the United States and Great Britain.

In South Asia, on the other hand, approximately 35% preferred injections. In Latin America, around 25% chose shots. The investigators found cultural differences in whether people thought various routes would be painful, acceptable, fast-acting and effective.

Suddenly, an obscure research question has real-world relevance for millions of people trying to lose weight.

A Weight Loss Revolution that Started with a Needle Has Evolved to Weight-Loss Pills

Some of the most successful weight-loss drugs ever developed by the pharmaceutical industry arrived in an unlikely package. They had to be injected.

Semaglutide became famous first as Ozempic for diabetes and then Wegovy for weight management. Tirzepatide became Mounjaro for diabetes and Zepbound for weight loss.

Many people who would ordinarily go out of their way to avoid needles learned to inject themselves. Why?

Because these medications could produce something earlier diet drugs often could not: substantial and sustained weight loss for many patients. One of my tennis partners decided that he needed to lose weight. To be fair, he was not wrong. D.L. was probably about 50 pounds overweight. He started self-injecting one of the new GLP-1 weight loss drugs. And at last count, he had lost over 40 pounds and looks great.

But what happens when the needle is no longer necessary? When I asked D.L. if he would be switching to the oral medicine, he said no. He was perfectly happy with the progress he had made with the shot.

The Pros and Cons of Weight-Loss Pills vs. Injections:

We recently received this question:

Q. What is a good, reliable pill for losing weight?

Here is our answer:

A. The landscape for weight loss has shifted dramatically in the last several years. The buzz around self-injected semaglutide (Ozempic, Wegovy) for type 2 diabetes and obesity demonstrated a highly effective strategy for weight loss utilizing the GLP-1 agonist pathway.

There are now two GLP-1 prescription pills that can help people shed pounds. Wegovy is available as a weekly injection or a daily pill. The oral form of this medication must be taken with four ounces of water at least 30 minutes before eating food or drinking other beverages.

The other weight-loss pill is Foundayo (orforglipron). It is newer and can be taken once daily with or without food.

Both oral medications are effective for weight loss, and both tend to produce gastrointestinal reactions such as nausea, vomiting, diarrhea, stomach ache, constipation and heartburn. There are less common but serious side effects you will want to discuss with your healthcare provider.

Oral Wegovy Changes the Weight-Loss Pills Equation

The active ingredient in Wegovy is semaglutide. People who use injectable Wegovy administer it once a week. The tablet is taken once a day. For someone terrified of needles, that may sound like a tremendous improvement. But there is a catch.

Oral semaglutide doesn’t move easily from the digestive tract into the bloodstream. Consequently, the Wegovy tablet has to be taken under rather specific conditions. The official prescribing instructions advise that it should be swallowed first thing in the morning on an empty stomach with no more than four ounces of plain water. We got into hot water because of a newspaper column we wrote a few months ago:

Q. In your newspaper column a few weeks ago you stated in reply to a question about oral Wegovy that the tablets “need to be taken with a big glass of water.” That is not what my Wegovy pill bottle instructions say. In fact, it says to take “with no more than 4 ounces of water.”

The advice you gave, if incorrect, might lead users to use it ineffectively. Please print a correction.

A. You are absolutely correct. The instructions from the maker of the Wegovy (semaglutide) pill state:

“Wake up and take 1 Wegovy pill on an empty stomach with a sip of water (up to 4 ounces).”

Thank you for catching our error.

We were properly embarrassed. We do our best to avoid such errors. We offered a correction to our newspaper column readers.

Here is the Bottom Line on Wegovy Weight-Loss Pills

The patient must wait at least 30 minutes before eating breakfast, drinking coffee or another beverage, or taking other oral medicine. That might be effortless for one person and downright irritating for another.

The payoff can be impressive. The clinical trial described in the FDA-approved prescribing information notes that people receiving the 25-mg oral Wegovy dose lost an average of 13.6% of their body weight over 64 weeks. Participants taking placebo lost about 2.4%.

About 47% of the people assigned to oral Wegovy lost at least 15% of their starting weight.

Foundayo: Weight-Loss Pills Without the Morning Ritual

Foundayo (orforglipron) represents a somewhat different technological advance. Although both drugs are GLP-1 receptor agonists, they get into the bloodstream differently. I could easily overwhelm you with pharmacology, but let me try to keep this simple.

Semaglutide is a peptide. That means it is a big molecule, a bit like a protein. It would normally be chewed up in the stomach by enzymes. The pharmaceutical manufacturer came up with a novel system utilizing an absorption enhancer to get the active drug into the blood stream. That is apparently why there is detailed information about 4 ounces of water and 30 minutes of wait time.

Unlike semaglutide, orforglipron is not a peptide. It is a small-molecule GLP-1 receptor agonist designed to work when swallowed. That means it can be taken once a day without the elaborate fasting and water restrictions required for oral semaglutide.

In a large clinical trial, people with obesity taking the highest dose of orforglipron lost an average of about 11.1% of their starting weight over 72 weeks, compared with 2.1% among those taking placebo.

We would caution against looking at 13.6% for Wegovy and 11.1% for Foundayo and declaring a winner. The drugs weren’t being compared against each other in the same study. Head-to-head trials would provide a much more reliable answer.

Americans Love Pills. But Are Pills Always Easier?

Here’s where this gets interesting. Suppose you hate needles the way my mother did. A daily tablet sounds like liberation. But a weekly injection requires remembering your medicine roughly 52 times a year. A daily pill requires remembering it 365 times.

With oral Wegovy, those 365 doses also have to fit around breakfast, coffee and other morning medicines. Suddenly, the “easy” choice may not be so obvious for everyone.

For another person, however, no amount of convenience will make an injection attractive. That person may gladly rearrange breakfast to avoid a needle. That is why individual preference matters!

In Some Countries, the Shot May Feel Like Strong Medicine

Our assumptions about medicine are partly learned. In the United States, being offered a pill instead of a shot may feel like progress. In some other cultures, an injection has historically conveyed the opposite message.

Researchers have described beliefs that a shot works faster, is more powerful or represents more serious medical treatment. The international survey we cited earlier found substantially greater enthusiasm for injections in South Asia, Latin America, the Baltic region and African-Islamic cultures than among respondents in English-speaking countries.

That doesn’t mean people elsewhere enjoy being stuck with needles. Rather, the meaning attached to an injection can be different. A patient may think: If the doctor or nurse is giving me a shot, I must be getting the strong stuff.

An American patient might think: If you can put the same medicine in a pill, why on earth are you coming at me with that needle?

Neither reaction is dictated by pharmacology.

What About Suppositories?

There is an even more striking demonstration that our ideas about how medicine “should” be taken are cultural. Rectal suppositories are uncommon enough in the United States that many adults would recoil at the suggestion.

They have traditionally been much more acceptable in several European countries, especially for treating young children who cannot or will not swallow medicine. When I was in graduate school in the pharmacology department at the University of Michigan, one professor asserted that the French pharmaceutical literature documented suppositories as an acceptable dosage form for various medications.

The international researchers found that even preferences involving rectal and vaginal medicines varied with cultural background. What seems perfectly ordinary in one medical culture can seem almost bizarre in another.

The Real Question Isn’t Just Which Weight-Loss Drug Works

For a long time, people interested in the remarkable effectiveness of GLP-1 medicines had to decide whether they were willing to inject themselves. Now the decision is becoming more complicated.

• How much weight might I lose?
• What are the side effects?
• What will the medicine cost?
• Will my insurance cover it?
• Do I want a treatment I take every day or once a week?

And finally:

Would I rather take a pill or give myself a shot?

There is no culturally correct answer and there may not even be one medically correct answer for everyone. But having a choice is itself a major change in the treatment of obesity.

Final Words

Did you find this article of interest? If so, we would be grateful if you shared it. We would also love to learn if you have used one of the newer weight-loss pills or an injectable medication. How well did it work? Did you experience any side effects?

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