Liraglutide vs Semaglutide: What the STEP 8 Head-to-Head Trial Found

Liraglutide and semaglutide are both GLP-1 receptor agonists, medicines that copy a gut hormone called GLP-1 to slow stomach emptying, reduce appetite and help control blood sugar. The main differences are how long they last in your body and how often you inject.

Liraglutide is the older drug. It is sold as Victoza for type 2 diabetes and as Saxenda for weight management. Saxenda is injected once a day, and the dose is raised in steps of 0.6 mg each week until you reach 3.0 mg, which takes about five weeks.

Semaglutide is newer and is built to last longer in the body. That is why it can be injected once a week. It is sold as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for weight management. The Wegovy dose rises slowly over about 16 to 20 weeks to a maintenance dose of 2.4 mg.

Both drugs act on the same receptor. Semaglutide simply binds more tightly and stays active longer, and the trials suggest that translates into more weight loss. If you want a deeper look at how this class works, see our explainer on [how GLP-1 medications actually work](/blog/how-do-glp1-medications-actually-work-mechanism).

STEP 8 showed that semaglutide 2.4 mg once weekly led to much more weight loss than liraglutide 3.0 mg once daily. It is the only major randomized trial that compared the two weight loss doses head to head (Rubino et al., JAMA 2022).

The trial enrolled 338 adults with overweight or obesity who did not have diabetes. They were assigned to semaglutide, liraglutide, or a matching placebo for each drug, and treatment lasted 68 weeks. All groups also got lifestyle counseling on diet and activity.

Average weight loss was 15.8% with semaglutide, 6.4% with liraglutide, and 1.9% with placebo. The share of people who lost at least 10% of their body weight was about 71% on semaglutide, about 26% on liraglutide and about 16% on placebo. The difference between the two drugs was about 9.4 percentage points of body weight, which is a large gap.

Two cautions help put this in context. First, the study compared the drugs in an open-label way, which means participants knew which drug they had, though each drug had its own placebo. Second, an average hides a lot of variation. Some people on liraglutide lost a lot, and some on semaglutide lost little. Still, the gap was big enough that most doctors now start with semaglutide or tirzepatide when weight loss is the goal.

The side effects are very similar, because both drugs work on the same gut and brain pathways. The most common ones are nausea, diarrhea, constipation, vomiting and reduced appetite. In STEP 8, stomach side effects were reported by most people on either drug, and they were usually mild to moderate and faded as the body adjusted.

A few differences stand out. Daily dosing with liraglutide means more injections, so there are more chances for injection site irritation. Some people say liraglutide's effects wear off between doses, which can make hunger feel more variable, while weekly semaglutide gives a steadier peak and valley across the week. Others feel the opposite, with the weekly peak causing a rough day or two after injection.

Serious risks are rare but shared. Both carry a boxed warning about thyroid C-cell tumors seen in rodents, and neither should be used by people with a personal or family history of medullary thyroid cancer or MEN 2. Gallbladder problems and pancreatitis have been reported with both. Our review of [what the thyroid data shows](/blog/glp1-thyroid-cancer-risk-what-the-data-shows) explains the human evidence, which has not confirmed that risk so far.

If nausea is your main worry, slow dose steps help with either drug. Ask your prescriber about staying on a dose longer before going up.

Both drugs have shown heart benefits in people at high cardiovascular risk, but the data comes from different groups. Liraglutide was tested in the LEADER trial (Marso et al., NEJM 2016) in about 9,300 people with type 2 diabetes. It lowered the risk of major cardiovascular events such as heart attack, stroke or cardiovascular death by about 13%, with a hazard ratio of 0.87.

Semaglutide was tested in the SELECT trial (Lincoff et al., NEJM 2023) in about 17,600 adults with overweight or obesity and existing heart disease but no diabetes. It lowered major cardiovascular events by 20%, with a hazard ratio of 0.80. You can read our summary in [SELECT: what the trial found about heart health](/blog/glp1-heart-health-what-the-select-trial-found).

Because the trials enrolled different groups, you cannot say that one drug protects the heart better than the other. What you can say is that both drugs have outcome data, which is more than many other weight loss medicines can claim.

If you are choosing a medicine for midlife weight gain, your own heart risk matters. High blood pressure, cholesterol and blood sugar often rise around menopause, and your doctor can help weigh the options for you.

Cost is where liraglutide can sometimes win. Liraglutide has been on the market longer, and generic versions have reached the US market, which can lower the price compared with brand-name drugs. Prices change often, so check current cash prices and insurance rules before you decide.

Semaglutide has strong access through savings programs and cash-pay options for Wegovy, but coverage still depends on your plan. Many plans cover GLP-1 drugs for type 2 diabetes more readily than for weight loss alone. Our guide to [GLP-1 savings cards and cash prices](/blog/glp1-savings-cards-cash-prices-lower-cost-2026) has current options.

Be careful with compounded versions. Compounded drugs are made by pharmacies and are not FDA-approved, so strength and purity can vary. Our article on [compounded versus brand GLP-1s](/blog/compounded-vs-brand-glp1-what-changed-2026) explains what changed and what to ask a pharmacy.

Also think about the real cost of a missed dose. A weekly shot is easy to fit into a routine, but a daily shot means traveling with supplies and needing a plan every single day. For some people the lower sticker price is worth that. For others, the convenience of weekly dosing pays for itself.

Both drugs start low and rise slowly, but the daily and weekly schedules feel quite different in practice. This slow climb is called titration, and it exists to give your gut time to adapt and keep nausea down.

With liraglutide, you inject once a day and increase the dose every week for five weeks: 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and then 3.0 mg. If a step causes too much nausea, many prescribers pause for another week before going up. You will inject about 365 times a year.

With semaglutide, you inject once a week, with steps every four weeks: 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg. That is about 52 injections a year. Because the drug lasts around a week in your body, a missed dose can often be taken within a few days, and our guide on [what to do after a missed GLP-1 dose](/blog/missed-glp1-dose-what-to-do-timing-guide) explains the timing rules.

Neither drug gets full effect right away. Appetite changes show up in the first weeks, but most of the weight loss builds over many months. In STEP 8, the gap between the two drugs kept widening through the 68 weeks of the trial.

Whichever you choose, take your time on the dose steps. Faster is not better, and the people who do best are usually the ones who can stay on treatment comfortably.

Liraglutide can still be a good choice for some people, even though semaglutide lost more weight on average. Here are the most common reasons.

Some people choose it because of price or insurance. If a plan covers one drug and not the other, or a generic is cheaper, that can decide it. Others want a drug with a long safety record. Liraglutide has been used in people for over a decade, including in adolescents with obesity in clinical trials, so doctors know its behavior well.

Some people tolerate a smaller daily dose better than a bigger weekly one. Daily dosing can feel gentler to those who get strong nausea for days after a weekly shot. And if you are trying to conceive soon, a drug with a shorter washout time matters. Liraglutide clears faster than semaglutide, though you should always stop GLP-1 medicines ahead of a pregnancy as your doctor advises. Our guide on [GLP-1s and pregnancy planning](/blog/glp1-fertility-pregnancy-planning-when-to-stop) explains timing.

If you are on liraglutide and stalling, you do not have to stay. Many people move up to semaglutide or tirzepatide. Our guide on [switching from Ozempic to Mounjaro](/blog/switching-from-ozempic-to-mounjaro-when-and-how) outlines how doctors handle dose changes between GLP-1 drugs.