What’s more effective, Ozempic, Mounjaro, Trulicity, or another drug entirely? Which causes more weight loss? Which lowers A1C more effectively?

The medications known as GLP-1 receptor agonists don’t just powerfully lower your blood sugar — they can also offer weight loss and protection against cardiovascular diseases. Those are benefits that most older diabetes drugs (such as sulfonylureas, DPP-4 inhibitors, and insulin) just can’t claim.

This article will look at the best and most rigorous studies of the newer type 2 diabetes drugs and will share the data.

What Are GLP-1 Receptor Agonists?

Glucagon-like peptide 1 (GLP-1) is a hormone that stimulates insulin secretion after you eat — it helps you feel full and regulates your blood sugar. In people with type 2 diabetes, however, this healthful hormone release and response can be ineffective or absent. GLP-1 receptor agonists are drugs that mimic the effect of GLP-1. They help your body use both GLP-1 and insulin properly, helping to keep blood sugar levels steady after meals.

One related drug, tirzepatide (Mounjaro), also mimics a second hormone named glucose-dependent insulinotropic polypeptide (GIP). Tirzepatide is formally classed as a dual GIP/GLP-1 receptor agonist, though it is casually grouped together in the same drug family as GLP-1 receptor agonists.

These drugs can also help you feel full after eating. People using GLP-1 receptor agonists often find themselves naturally eating fewer calories, leading to effortless weight loss.

The first GLP-1 receptor agonist reached the market over a decade ago, but it’s still fair to consider them “new.” Diabetes authorities have only gradually endorsed their use over older drugs, and some clinicians have been slow to recommend them to their patients. It’s taken a social media-fueled craze to really bring them to mainstream attention.

Most people with type 2 diabetes will only be prescribed a GLP-1 receptor agonist if metformin and lifestyle changes have not been enough to keep their blood sugar well-controlled. However, diabetes authorities have recently moved to recommend GLP-1 inhibitors earlier for patients, even patients with new-onset type 2 diabetes, especially if they have overweight, obesity, or atherosclerotic cardiovascular disease.

Sadly, there’s another major factor that’s slowed down the adoption of GLP-1 receptor agonists — they’re incredibly expensive. Ozempic currently has an off-the-shelf price of about $900 per month in the United States, and it may be over a decade before an approved generic version becomes available. The price you pay, of course, will likely depend utterly on the details of your health insurance plan.

Every GLP-1 Receptor Agonist

The following lists every GLP-1 receptor agonist that is currently approved in the United States for the treatment of type 2 diabetes.

Semaglutide (Ozempic) — a weekly injection
Semaglutide (Rybelsus) — a daily pill
Tirzepatide (Mounjaro) — a weekly injection
Liraglutide (Victoza) — a daily injection
Dulaglutide (Trulicity) — a weekly injection
Exenatide (Bydureon BCise) — a weekly injection
Exenatide (Byetta) — a twice-daily injection

Two of the drugs above are also marketed under different names as a weight loss therapy for people without diabetes: semaglutide (Wegovy) and liraglutide (Saxenda). It is widely expected that tirzepatide will win a similar approval from the FDA soon. 

Whether all of these drugs are actually available is another question entirely. The manufacturers of semaglutide and tirzepatide have been unable to satisfy the unprecedented demand for their drugs, fueled by their popularity as weight-loss treatments. Persistent shortages have made it difficult for people with diabetes to find the Ozempic and Mounjaro they’ve been prescribed, and the makers have intermittently paused their marketing efforts or the production of starter doses.

How We Compared Drugs

It’s not always easy to compare the effects of one drug against another, because the clinical trials that provide our most rigorous data do not share identical baselines.

Drugmakers test their new drug candidates in many distinct trials, assessing the effects on different types of people over different periods of time. Ozempic, for example, was the subject of at least fifteen different major final-phase trials in people with type 2 diabetes. One experiment, for example, evaluated the drug in those also using basal insulin, another in those also using an SLGT-2 inhibitor, another in people with high cardiovascular risk, another with patients outside of the US and Western Europe, and so on.

We did our best to find a level playing field. We’ve pulled the data from the longest phase 3 trials that tested the maximum approved dosage of each drug. The participants of these studies were adults with type 2 diabetes who had been otherwise using standard treatment (typically metformin, with or without additional oral drugs such as sulfonylureas or pioglitazone). We avoided trials that tested the drugs in new patients or in those with established cardiorenal complications.

Comparing GLP-1 Receptor Agonists

Semaglutide (Ozempic)

There’s a reason it’s the world’s buzziest diabetes drug: Ozempic delivers impressive glucose improvement and weight loss. This weekly injection is so popular that, well over a year after demand spiked due to a social media craze, shortages are still making it difficult for people with diabetes to find the drug. (This, in turn, has led some patients to turn to potentially dangerous sources of off-brand Ozempic).

Ozempic also reduces the risk of severe cardiovascular outcomes, and there is early evidence that it may help prevent or treat chronic kidney disease, too. The manufacturer recently decided to conclude its pivotal kidney outcomes trial early because the evidence that it would succeed was overwhelming.

Semaglutide (Rybelsus)

Rybelsus is essentially Ozempic in pill form. The semaglutide in a pill is just as potent as the semaglutide in an injected solution, but Rybelsus has less powerful effects than Ozempic because it is only available in lower dosages. (The manufacturer is studying higher doses and may seek FDA approval soon).

Rybelsus is also kind of a hassle to take. According to the FDA label, you need to take Rybelsus on an empty stomach, every morning, 30 minutes before eating, drinking, or using any other oral medications. You may have up to 4 ounces of plain water only during this time. If you have your breakfast too early, the pill will be less effective. 

Nevertheless, it’s still a very effective drug, and may be an especially attractive option for people with needle phobia.

Tirzepatide (Mounjaro)

Mounjaro, strictly speaking, is not a GLP-1 receptor agonist but a dual GIP/GLP-1 receptor agonist; it mimics the function of a second hormone, which is possibly the secret of its effectiveness.

It seems fair to say that Mounjaro is the most powerful drug in this family that is currently available. It offers the most weight loss for people with diabetes, with glucose-lowering effects that are better than Ozempic’s.

At the moment, Mounjaro is too new to know what kind of heart and kidney health benefits it might offer. That research is occurring right now. Early data suggests that it will offer protection for the heart and kidneys, but diabetes authorities are waiting for the outcomes of major trials dedicated to the question before they render an official judgment.

Dulaglutide (Trulicity)

Although not quite as buzzy as Ozempic or Mounjaro, Trulicity is nearly as effective, offering truly significant weight loss and glucose-lowering effects, especially at its highest dosage. It is also known to protect heart health and may help protect the kidneys.

Liraglutide (Victoza)

Victoza appears to be slightly less powerful than most of its competitors in the GLP-1 family of drugs. It also requires a daily injection, rather than a weekly one, which may make it less appealing.

Still, Victoza is a significant step up from metformin, and causes enough weight loss to have been approved as an obesity medication (when labeled as Saxenda). It is also known to have cardioprotective effects and may help protect against kidney disease.

Exenatide (Bydureon BCise, Byetta)

Exenatide is the least heavily hyped GLP-1 available. 

Bydureon BCise is not as powerful as other options in the class, but it can still have strong positive effects for people with type 2 diabetes, including both weight loss and A1C reduction.

We omitted Byetta from the chart above because it is generally considered a less attractive option. In fact, it appears that the manufacturer is barely marketing the drug anymore. Byetta is a shorter-acting version of exenatide and requires much more fuss: two daily injections, one each within an hour of breakfast and dinner. It’s also slightly less effective than Bydureon. 

Heart and Kidney Health Benefits

This article has concentrated on glucose control and weight loss, perhaps the two central goals of type 2 diabetes management. However, some GLP-1 receptor agonists offer additional benefits.

The most important of these benefits is probably protection from cardiovascular and kidney disease, two of the most common causes of early death in people with type 2 diabetes.

According to the American Diabetes Association, three GLP-1 receptor agonists offer heart health protection: liraglutide, semaglutide, and dulaglutide. The ADA recommends all three GLP-1 receptor agonists as preferred treatments for people with either demonstrated atherosclerotic cardiovascular disease or a high risk of it.

There is also encouraging evidence that the same three drugs offer kidney protection, but the data isn’t definitive yet. Patients with chronic kidney disease are recommended to use SGLT2 inhibitors first, only adding a GLP-1 receptor agonist if they do not tolerate the drug or need more pharmaceutical help getting blood sugar levels under control.

At the moment, tirzepatide (Mounjaro) is too new to know what kind of heart and kidney health benefits it might offer. That research is occurring right now. Early data suggests that it will offer protection for the heart and kidneys, but diabetes authorities are awaiting the outcomes of major trials dedicated to the question before they render an official judgment.

Side Effects

If you’ve paid attention to social media lately, you know that Ozempic is associated with a dizzying number of side effects. A sizable percentage of users endure gastrointestinal troubles such as nausea, vomiting, and diarrhea. There are also risks of rare but serious complications such as gastroparesis (stomach paralysis), medullary thyroid cancer, gallstones, and pancreatitis. Some users who have successfully slimmed down have complained about “Ozempic face” and hair loss. Other drugs in the GLP-1 receptor agonist family have broadly similar effects, though individual medications will differ in the details.

Though it may be safe to assume that more powerful GLP-1 receptor agonists also induce more side effects, that isn’t necessarily the case. Mounjaro, for example, causes nausea and vomiting in about 18 percent and 9 percent of patients, according to its FDA label (PDF), which is slightly less than the numbers reported for Trulicity (PDF). Within any one particular drug, however, higher dosages nearly always create a greater incidence of side effects.

If you are particularly concerned about adverse reactions, let your doctor know so that they can be sure to select a medication that fits your own health situation best.

Takeaways

The new family of GLP-1 receptor agonists is taking the diabetes world by storm. These drugs offer remarkable health benefits, particularly enhanced blood sugar control and weight loss that can seem effortless.

The several drugs in this family differ in many ways, including delivery method, glucose-lowering efficacy, weight-loss efficacy, and cardioprotective strength.

To be clear, this article is not expert advice. It has been reviewed by a doctor for accuracy, but it was not written by a doctor and does not attempt to recommend individual drugs. While we hope that this analysis will provide some food for thought, only a clinician can determine which medications are right for you.

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