How does Oforglipron compare?

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Novo Nordisk’s semaglutide, Pfizer’s danuglipron, and Eli Lilly’s oforglipron are three medications that belong to a class of drugs called GLP-1 agonists.

But what sets these apart from other GLP-1 agonists is the way they’re administered – they come in the form of pills, which can be taken orally once or twice a day, eliminating the need for injections or needles.

Now, you might be wondering, why is this such a big deal? Well, it caters to those who prefer the ease of swallowing a pill rather than dealing with needles or injections.

However, comparing these three pills to each other is not a straightforward task, as they are at different stages of development.

In fact, danuglipron has not even been tested in healthy individuals without diabetes yet. This poses a challenge when comparing it to the other two drugs, since we can only analyze studies that focus on weight loss in diabetic patients.

Why is this important, you may ask? Well, it turns out that individuals with diabetes tend to experience less weight loss compared to healthy individuals when taking these medications. Several factors contribute to this, including insulin resistance and metabolic differences, which can make weight loss more challenging for diabetic patients overall.

So how do they compare and which one will be the winner?

Semaglutide vs Danuglipron vs Orforglipron

While all three medications come in the form of pills, there are some differences when it comes to how to properly take them.

Semaglutide, for instance, requires you to take it on an empty stomach, with no more than 4 ounces of plain water, in order to maintain its optimal effectiveness.

On the other hand, danuglipron and oforglipron seem to be more flexible in this regard. You can take them at any time, whether your stomach is empty or full.

What about effectiveness for weight loss? Although direct head-to-head comparisons between these medications are lacking, we can draw some indirect conclusions.

When it comes to weight loss in diabetic patients, those who used 50 mg of semaglutide achieved an average loss of around 8 kilograms. Similarly, individuals taking oforglipron experienced a similar degree of weight loss, with an average of 7.9 kilograms.

However, when it comes to danuglipron, the average weight loss was slightly lower, at around 5 kilograms.

But weight loss is not the only factor we need to consider. Let’s talk about managing diabetes. Here, too, we see a similar trend.

Semaglutide at 50 mg and oforglipron both demonstrated a reduction in HbA1c levels, which is a measure of long-term blood sugar control, by approximately 2% and 1.7%, respectively. On the other hand, danuglipron showed a more modest reduction of 1.3%.

Limitations to comparison

So semaglutide and oforglipron appear to be quite comparable in terms of their effectiveness, while danuglipron seems to lag behind a bit.

However, it’s actually not that cut and dry. We must consider another crucial factor: the duration of the trials conducted.

Patients taking semaglutide took it for 68 weeks to achieve those impressive results. On the other hand, oforglipron was evaluated over a period of 26 weeks, which is less than half the time, while danuglipron’s trial was even shorter at just 12 weeks.

When one takes into account that danuglipron was only used for a duration that’s 5 to 6 times shorter than semaglutide, the real differences in weight loss may not be as obvious.

Some speculate that the shorter duration of danuglipron’s trial indicates faster results, as it achieved over 60% of the weight loss seen with semaglutide in less than one-fifth of the time.

However, this speculation is not accurate. Weight loss with these medications doesn’t follow a linear path. The initial months often show the most rapid progress, after which the pace slows down or even reaches a plateau.

At this stage, the medication’s ability to sustain and maintain weight loss in the long run becomes more crucial. Otherwise, we risk the all-too-common issue of weight regain often associated with short-term drugs like phentermine.

So with that in mind, which of these three medications is the most effective for weight loss or diabetes? Unfortunately, until danuglipron and oforglipron complete their Phase 3 trials, we won’t have definitive answers.

However, if I were to venture a guess as to which could potentially be the most effective, my bet would be on oforglipron. Its effects on weight loss and HbA1c levels do look promising at the 28-week mark.

That being said, I also believe that the differences between these three GLP-1 drugs will likely be negligible from a consumer perspective.

Patients who choose any of these three options are likely to find them all effective in their journey towards weight loss and diabetes management.

Ultimately, the preference may come down to the cost factor. Consumers might lean towards the option that is more frequently covered by insurance or comes with a lower overall price tag. The cheapest and most accessible option will likely be the preferred choice for most people.

Side effects

Let’s talk about the side effects. All three drugs have similar side effect profiles, with nausea, vomiting, and diarrhea being the most commonly reported ones.

However, comparing the frequency or overall tolerability of each drug is quite challenging due to the differences in how these adverse events were reported across the studies. So I can only guess which one is least or most tolerable.

However, if I were to speculate based solely on the information provided in the studies, it seems that danuglipron might be tolerated the poorest among the three.

In the study, they note that a significant proportion of participants (72.7%) had to discontinue taking the medication at the maximum dose, compared to only 18.8% in the placebo group. And the primary reason for discontinuation was adverse events.

This means that over half of the participants taking danuglipron at the maximum dose chose to drop out of the study due to side effects.

Interestingly, danuglipron does not even have the highest rates of nausea or vomiting compared to the other drugs, which suggests that there might be other side effects that are causing individuals to voluntarily discontinue the drug.

It’s worth noting, however, that these observations are drawn from a small Phase 2 trial, as larger trials are not available at the moment. Therefore, we must recognize that we have an incomplete picture, and additional data will be necessary to draw more accurate conclusions.

Are GLP-1 pills better?

Let’s address a common question that arises amidst the growing availability of these GLP-1 pills: Are these pills as effective as the GLP-1 injections?

There seems to be a misconception that injections may offer superior effectiveness compared to pills. One reason for this belief is the notion that oral formulations are not as well absorbed as their injected counterparts.

While this can be true in some cases, it’s important not to confuse absorption with effectiveness. If an oral formulation has lower absorption, assuming it can be taken orally, a common solution is simply to increase the dose until the desired effectiveness is achieved.

Let’s take semaglutide as an example. The injectable form for diabetes is typically administered at a 1 mg dose, whereas the oral form is taken at a 14 mg dose, which is equivalent to a fourteenfold increase.

Similarly, for weight loss, the injectable Wegovy, is given at a 2.4 mg dose, while the oral form is taken at a 50 mg dose, representing a more than twentyfold increase.

This demonstrates that pill formulations are carefully designed to achieve comparable effectiveness to their injected counterparts.

In fact, any differences in effectiveness are likely to be influenced more by patient compliance rather than the delivery method itself.

For instance, for some individuals, remembering to administer an injection once a week may be easier than taking a pill every day, especially if the pill needs to be taken in the morning on an empty stomach each time.

Skipping doses due to forgetfulness or taking the pills with food for convenience can reduce their efficacy. In such cases, injections may be more effective for certain individuals based on their lifestyle and preferences.

Dr. Brian’s review

It’s important for me to acknowledge right now that it might be a little too early to make accurate comparisons between them. And with the continuous emergence of new GLP-1 agonists, both oral and injected, there will be a wider range of options available to consumers to compare against each other.

Currently, there is a lot of excitement and speculation surrounding which drug will be the most effective.

Attention-grabbing headlines boasting 20% or even 24% weight loss with the latest drug, retatrutide, contribute to the hype. This buzz helps generate consumer demand for these newer medications.

However, I believe that over time, as more of these drugs enter the market, the hype will settle down. We will begin to see that many of these medications offer similar effectiveness when it comes to weight loss.

At that point, other factors will come into play. I think affordability and accessibility will drive demand. The winner will be the drug that can provide an effective treatment at the most affordable price, rather than who has the highest percentage weight loss, especially when the difference will only be a few percent.

Learn more about

• Semaglutide vs Danuglipron
• Comparing other GLP-1 Agonists for Weight Loss
• Other weight loss medications

See also

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