Semaglutide vs. Liraglutide: GLP-1 Comparison

Two drugs. Same target receptor. Very different results. Semaglutide (sold as Ozempic and Wegovy) and liraglutide (sold as Victoza and Saxenda) both belong to the GLP-1 receptor agonist class, and both were developed by the same company -- Novo Nordisk. But the differences between them are not minor. In randomized trials, semaglutide has produced roughly 2.5 times more weight loss than liraglutide. It works once a week instead of once a day. And it appears to offer stronger cardiovascular protection.

Yet liraglutide arrived first, established the class, and now offers something semaglutide cannot: a generic version. For millions of patients weighing cost against efficacy -- or tolerability against convenience -- the choice between these two GLP-1 agonists is anything but simple.

This article breaks down the clinical evidence, pharmacology, side effects, and practical considerations. No vendor claims. No hype. Just what the trials and the science actually show.

How GLP-1 Agonists Work
Quick Comparison Table
The Molecular Story: Why One Lasts Longer
Blood Sugar Control: SUSTAIN 10 and Beyond
Weight Loss: STEP 8 Settles the Debate
Cardiovascular Outcomes: LEADER vs. SUSTAIN-6
Side Effects and Tolerability
Dosing and Administration
Formulations and Brand Names
Cost and Generic Availability
Who Might Prefer Which Drug
The Bottom Line
Frequently Asked Questions
References

How GLP-1 Agonists Work

Both semaglutide and liraglutide mimic a naturally occurring hormone called glucagon-like peptide-1, or GLP-1. Your gut releases this hormone after eating. It tells the pancreas to produce insulin, signals the liver to slow glucose output, delays stomach emptying, and acts on brain regions that regulate appetite and satiety.

The problem with native GLP-1 is that it survives for about two minutes in the bloodstream before an enzyme called dipeptidyl peptidase-4 (DPP-4) chews it up. Both liraglutide and semaglutide solve this problem through a shared strategy: they attach fatty acid chains to the GLP-1 molecule, which makes it bind to albumin -- the most abundant protein in blood plasma. Albumin acts as a circulating shield, protecting the drug from degradation and slowing its clearance through the kidneys.

For a deeper look at the mechanism, see our guide on how GLP-1 medications work.

Where the two drugs diverge -- and why semaglutide lasts so much longer -- comes down to molecular engineering.

Quick Comparison Table

Feature	Semaglutide	Liraglutide
Brand names (diabetes)	Ozempic, Rybelsus	Victoza
Brand names (weight loss)	Wegovy	Saxenda
Dosing frequency	Once weekly (injectable) or once daily (oral)	Once daily (injectable only)
Half-life	~7 days (168 hours)	~13 hours
Max dose (diabetes)	2 mg/week (Ozempic) or 14 mg/day (Rybelsus)	1.8 mg/day (Victoza)
Max dose (weight loss)	2.4 mg/week (Wegovy)	3.0 mg/day (Saxenda)
HbA1c reduction (head-to-head)	-1.7% (SUSTAIN 10)	-1.0% (SUSTAIN 10)
Weight loss (head-to-head)	-15.8% at 68 weeks (STEP 8)	-6.4% at 68 weeks (STEP 8)
Cardiovascular risk reduction	26% (SUSTAIN-6)	13% (LEADER)
Oral formulation available	Yes (Rybelsus)	No
Generic available (U.S.)	No (expected early 2030s)	Yes (Teva, 2024-2025)
FDA approval year	2017 (Ozempic)	2010 (Victoza)
Pediatric approval	Adults only	Ages 10+ (Victoza)

The Molecular Story: Why One Lasts Longer

Native human GLP-1 is a 30-amino-acid peptide. Both liraglutide and semaglutide are modified versions of it, but their modifications differ in ways that produce dramatically different pharmacokinetic profiles.

Liraglutide is 97% identical to human GLP-1. It has one amino acid substitution (lysine-34 to arginine) and a C-16 palmitic acid chain attached at position 26 through a gamma-glutamic acid spacer. That fatty acid chain binds albumin with high affinity -- roughly 99% of circulating liraglutide molecules are albumin-bound at any given time. The result: a half-life of about 13 hours, long enough for once-daily dosing but requiring an injection every 24 hours.

Semaglutide pushes the same strategy further. It's 94% identical to human GLP-1, with two amino acid substitutions instead of one. The first (alpha-aminoisobutyric acid at position 8) makes the molecule almost completely resistant to DPP-4 degradation -- a weakness liraglutide only partially addresses. The second (arginine at position 34) enables attachment of a longer C-18 stearic diacid chain through a more complex linker. This longer fatty acid chain binds albumin more tightly than liraglutide's C-16 chain, and the DPP-4 resistance means the drug survives far longer once it does separate from albumin.

The combined effect is a half-life of approximately seven days -- roughly 13 times longer than liraglutide. That's the entire pharmacological basis for weekly versus daily dosing.

For full pharmacology details on each drug individually, see our semaglutide guide and liraglutide profile.

Blood Sugar Control: SUSTAIN 10 and Beyond

The most direct head-to-head comparison of these drugs for blood sugar control came from the SUSTAIN 10 trial, published in 2019. This phase 3b, open-label study enrolled 577 adults with type 2 diabetes across 11 European countries. All participants had inadequate blood sugar control on one to three oral medications (metformin, sulfonylureas, or SGLT-2 inhibitors).

Participants were randomized 1:1 to receive either semaglutide 1.0 mg once weekly or liraglutide 1.2 mg once daily for 30 weeks. These doses were chosen to reflect real-world clinical prescribing patterns rather than maximum approved doses.

The results

Starting from a mean baseline HbA1c of 8.2%, the semaglutide group dropped by 1.7 percentage points compared to 1.0 percentage points in the liraglutide group. The estimated treatment difference was -0.69% (95% CI: -0.82 to -0.56, P < 0.0001). Semaglutide was statistically superior.

More semaglutide-treated patients reached the target HbA1c levels that guidelines recommend:

HbA1c below 7.0%: Significantly more patients in the semaglutide group achieved this standard diabetes management target (P < 0.0001).
HbA1c at or below 6.5%: The more aggressive target was also reached by a significantly greater proportion of semaglutide patients (P < 0.0001).

A 2025 meta-analysis in Frontiers in Pharmacology, pooling 16 studies and 5,997 patients, confirmed these findings: semaglutide produced significantly greater HbA1c reductions than liraglutide across multiple study designs (weighted mean difference: 0.56; 95% CI: 0.19-0.94; P < 0.001). However, the meta-analysis found no significant difference for fasting blood sugar or BMI when pooling across different dose combinations. The HbA1c advantage was clear, but not every glycemic marker showed the same gap.

Weight Loss: STEP 8 Settles the Debate

If SUSTAIN 10 compared the diabetes doses, STEP 8 compared the weight-loss doses. Published in JAMA in January 2022, this randomized, open-label trial enrolled 338 adults with overweight or obesity (BMI 30 or greater, or 27 or greater with comorbidities) but without diabetes at 19 U.S. sites.

Participants were randomized to receive semaglutide 2.4 mg once weekly or liraglutide 3.0 mg once daily for 68 weeks, alongside counseling for diet and physical activity. A pooled placebo group provided the control comparison.

The weight loss numbers

At 68 weeks, mean body weight change was:

Semaglutide 2.4 mg: -15.8%
Liraglutide 3.0 mg: -6.4%
Pooled placebo: -1.9%

The treatment difference between semaglutide and liraglutide was -9.4 percentage points (95% CI: -12.0 to -6.8; P < 0.001). In absolute terms, semaglutide produced roughly 2.5 times more weight loss than liraglutide.

Threshold analysis

The categorical outcomes were equally striking. Compared to liraglutide, the odds of reaching clinically meaningful weight loss milestones with semaglutide were:

10% or more body weight loss: Odds ratio 6.3 (P < 0.001)
15% or more body weight loss: Odds ratio 7.9 (P < 0.001)
20% or more body weight loss: Odds ratio 8.2 (P < 0.001)

These are large effect sizes. For context, 10% weight loss is generally associated with meaningful improvements in blood pressure, cholesterol, and blood sugar. A 15% loss often resolves pre-diabetes.

For a detailed breakdown of the semaglutide weight loss program, see our STEP study breakdown.

The dropout factor

Here's something that surprised many clinicians: despite producing more side effects (more on that below), fewer people quit semaglutide. Treatment discontinuation rates were 13.5% for semaglutide versus 27.6% for liraglutide. The convenience of weekly dosing appears to outweigh the intensity of gastrointestinal side effects for most patients.

Cardiovascular Outcomes: LEADER vs. SUSTAIN-6

Cardiovascular disease is the leading killer of people with type 2 diabetes. Both drugs have been tested in large, rigorous cardiovascular outcome trials -- and both showed benefit. But the magnitudes differ.

LEADER (Liraglutide)

The LEADER trial, published in The New England Journal of Medicine in 2016, randomized 9,340 patients with type 2 diabetes and high cardiovascular risk to liraglutide 1.8 mg daily or placebo for a median of 3.8 years. The primary composite endpoint -- cardiovascular death, nonfatal MI, or nonfatal stroke -- occurred in 13.0% of the liraglutide group versus 14.9% with placebo: a 13% relative risk reduction (HR 0.87; 95% CI: 0.78-0.97; P = 0.01). Liraglutide also reduced all-cause mortality and kidney events. It was the first GLP-1 agonist to show cardiovascular benefit in a randomized trial.

SUSTAIN-6 (Semaglutide)

Published the same year in the NEJM, SUSTAIN-6 randomized 3,297 high-cardiovascular-risk patients to semaglutide (0.5 or 1.0 mg weekly) or placebo for 104 weeks. The same composite endpoint occurred in 6.6% of the semaglutide group versus 8.9% with placebo -- a 26% relative risk reduction (HR 0.74; 95% CI: 0.58-0.95; P < 0.001 for noninferiority), driven primarily by a 39% drop in nonfatal stroke.

An important caveat: SUSTAIN-6 was designed as a noninferiority trial; the 26% superiority finding was post-hoc. LEADER was nearly three times larger with longer follow-up. Direct numerical comparisons between the two trials should be made carefully -- they studied different populations over different durations using different statistical frameworks.

SUSTAIN-6 safety signal

SUSTAIN-6 flagged one concern that LEADER did not: a higher rate of diabetic retinopathy complications in the semaglutide group (3.0% vs. 1.8%; HR 1.76; P = 0.02). Subsequent analyses suggest this may relate to the speed of blood sugar improvement rather than a direct drug effect -- rapid HbA1c drops can temporarily worsen existing retinopathy, a phenomenon seen with insulin as well. But it bears monitoring in patients with pre-existing eye disease.

For more on the cardiovascular evidence across the GLP-1 class, see our GLP-1 cardiovascular outcomes meta-analysis.

Side Effects and Tolerability

Both drugs share the same core side effect profile: gastrointestinal symptoms. Nausea, vomiting, diarrhea, and constipation are the most common complaints with any GLP-1 agonist.

How the side effects compare

In STEP 8, adverse event rates were nearly identical between semaglutide 2.4 mg (95.2%) and liraglutide 3.0 mg (96.1%). The drugs cause similar types of problems at similar overall rates.

But there are practical differences:

Liraglutide's side effects tend to be milder on a per-episode basis. Because it's dosed daily and has a shorter half-life, the drug reaches steady state faster and any given bout of nausea passes more quickly. If a patient has a bad day, tomorrow's injection can be delayed or the dose adjusted the following day.

Semaglutide's side effects can be more intense during dose escalation. Because the drug has a seven-day half-life, side effects from a dose increase can persist for days. However, the 16-week dose escalation protocol (versus liraglutide's 4-week escalation) is designed to mitigate this by increasing the dose more gradually.

The paradox of discontinuation

Despite producing side effects that can feel worse in the moment, semaglutide had a significantly lower rate of treatment discontinuation due to adverse events in STEP 8: 3.2% versus 12.6% for liraglutide. The overall discontinuation rate told the same story: 13.5% for semaglutide versus 27.6% for liraglutide.

The most likely explanation is convenience. One injection per week is meaningfully easier than one per day, and patients seem willing to tolerate more discomfort when the treatment burden is lower.

Shared serious risks

Both drugs carry an FDA boxed warning about thyroid C-cell tumors based on rodent studies. Neither has shown this risk in humans, but both are contraindicated in patients with a personal or family history of medullary thyroid carcinoma or MEN2. Other shared risks include pancreatitis, gallbladder disease, and hypoglycemia when combined with insulin or sulfonylureas.

For practical guidance on managing these effects, see our article on how to manage GLP-1 side effects.

Dosing and Administration

Both drugs follow a "start low, go slow" escalation strategy to minimize GI side effects, but the timelines differ.

Liraglutide starts at 0.6 mg daily. For diabetes (Victoza), the dose escalates to 1.2-1.8 mg daily. For weight management (Saxenda), the target is 3.0 mg daily, reached at week five by increasing 0.6 mg each week. It can be injected any time of day, with or without meals.

Semaglutide starts at 0.25 mg weekly. For diabetes (Ozempic), the dose escalates to 0.5-2.0 mg weekly. For weight management (Wegovy), the escalation moves through five dose steps over 16 weeks to reach the target of 2.4 mg weekly. The slower ramp-up is intentional -- it gives the body more time to adjust to a drug with a seven-day half-life.

Oral semaglutide (Rybelsus) starts at 3 mg daily, escalating to 7 mg and potentially 14 mg. The oral form demands strict adherence: take on an empty stomach with no more than 4 oz of plain water, then wait 30 minutes before eating or taking other medications. Oral bioavailability is only 0.4-1% compared to 89% for the injectable form, which is why oral doses are measured in milligrams while injectable doses use fractions of a milligram.

Available Formulations and Brand Names

Semaglutide is sold under three brand names: Ozempic (injectable, for diabetes), Wegovy (injectable, for weight management), and Rybelsus (oral tablet, for diabetes). The FDA has also approved an oral Wegovy tablet (25 mg daily) for weight management, with the OASIS 4 trial showing 16.6% mean weight loss at 64 weeks.

Liraglutide is sold as Victoza (for diabetes) and Saxenda (for weight management), both injectable. No oral liraglutide exists.

This gives semaglutide a notable advantage for needle-averse patients. For more on the difference between semaglutide brand names, see our Ozempic vs. Wegovy comparison.

Cost and Generic Availability

This is where liraglutide has its clearest advantage.

Liraglutide: first GLP-1 with a generic

Teva Pharmaceuticals launched a generic version of Victoza (for diabetes) in June 2024 and received FDA approval for a generic Saxenda (for weight loss) in August 2025. These are the first generic GLP-1 medications available in the United States.

Current approximate monthly costs (without insurance):

Generic Victoza (liraglutide for diabetes): ~$470-700/month
Generic Saxenda (liraglutide for weight loss): ~$1,165/month
Branded Saxenda: ~$1,350/month

Prices should drop further as more generic manufacturers enter the market. Industry analysis suggests it typically takes four or more competitors before prices fall by 50-60%.

Semaglutide: still patent-protected

No generic semaglutide is available in the United States, and none is expected until the early 2030s based on current patent expirations. Some international markets may see generic versions sooner.

Current approximate monthly costs (without insurance):

Ozempic: ~$900-1,000/month
Wegovy: ~$1,300-1,400/month
Rybelsus: ~$900-1,000/month

Under a 2025 agreement, Medicare negotiated prices for Ozempic and Wegovy at $245/month, with a $50 patient copay. For Medicare beneficiaries, this significantly narrows the cost gap between semaglutide and generic liraglutide.

What the cost difference means in practice

For uninsured patients or those with limited coverage, generic liraglutide may be the only financially viable GLP-1 option. The efficacy gap is real, but a drug a patient can afford and take consistently will outperform a superior drug that sits unpurchased on a pharmacy shelf.

Who Might Prefer Which Drug

Semaglutide makes sense when maximum weight loss is the priority, when weekly dosing would improve adherence, when an oral option is preferred, or when stronger HbA1c reduction is needed.

Liraglutide makes sense when cost is the deciding factor (generic liraglutide is the cheapest FDA-approved GLP-1), when a pediatric patient needs treatment (Victoza is approved for ages 10+, while Ozempic is adults only), when milder day-to-day side effects matter, or when the patient has pre-existing diabetic retinopathy. Some clinicians also use liraglutide as a "stepping stone" -- establishing GLP-1 tolerability before transitioning to semaglutide. Research on this switch shows additional weight loss and blood sugar improvements after the transition.

For readers interested in how semaglutide compares to the newer dual agonist tirzepatide, see our semaglutide vs. tirzepatide comparison.

The Bottom Line

Semaglutide is the more effective drug by nearly every clinical measure. It produces greater weight loss, larger HbA1c reductions, and a numerically larger cardiovascular risk reduction, all while requiring fewer injections. In a vacuum, the data would favor semaglutide for most patients.

But medicine doesn't happen in a vacuum. Liraglutide has a longer track record (FDA-approved since 2010 versus 2017 for Ozempic), a generic option that meaningfully lowers cost, pediatric approval, and a tolerability profile that some patients find easier to manage. It remains a solid, evidence-backed GLP-1 agonist.

The practical decision often comes down to three factors: insurance coverage, side effect tolerance, and how much weight loss is needed. A patient whose insurance covers Ozempic or Wegovy with a manageable copay has little clinical reason to choose liraglutide. A patient paying out of pocket may find generic liraglutide provides enough benefit to justify the daily injection schedule.

Neither drug is wrong. Both represent a genuine advance over older diabetes and obesity treatments. The conversation to have is with a prescribing clinician who can weigh individual medical history, financial constraints, and treatment goals against this evidence.

Frequently Asked Questions

Can I switch from liraglutide to semaglutide?

Yes. Research shows that patients switching from liraglutide to semaglutide maintain their HbA1c improvements and often experience additional weight loss and fasting blood sugar reductions. Your doctor will determine the appropriate starting dose of semaglutide based on your current liraglutide dose and response.

Is Ozempic the same as Wegovy?

Both contain semaglutide, but they're approved for different indications at different doses. Ozempic (max 2.0 mg/week) is approved for type 2 diabetes. Wegovy (max 2.4 mg/week) is approved for chronic weight management. See our Ozempic vs. Wegovy comparison for the full breakdown.

Do both drugs work for weight loss if I don't have diabetes?

Wegovy (semaglutide 2.4 mg) and Saxenda (liraglutide 3.0 mg) are both FDA-approved for weight management in adults with BMI 30 or greater, or BMI 27 or greater with at least one weight-related comorbidity, regardless of diabetes status. Ozempic and Victoza are approved only for type 2 diabetes, though weight loss occurs as a secondary effect.

Which drug has fewer side effects?

The overall adverse event rates are similar (about 95-96% in STEP 8). Liraglutide's side effects tend to be milder per episode due to its shorter half-life, but it has a higher treatment discontinuation rate. Semaglutide's side effects can be more intense during dose escalation but are offset by once-weekly convenience. Neither drug is clearly "easier" across the board.

Will a generic semaglutide be available soon?

Not in the United States. Based on current patent expirations, generic semaglutide is not expected until the early 2030s. Some international markets may see generic versions sooner. Generic liraglutide (both the Victoza and Saxenda equivalents) is already available from Teva Pharmaceuticals.

Can I take oral semaglutide instead of injections?

Yes. Rybelsus is approved for type 2 diabetes, and an oral Wegovy tablet is approved for weight management. The oral form must be taken on an empty stomach with minimal water, 30 minutes before eating. Results are broadly comparable for blood sugar control, though injectable semaglutide at higher doses still leads for weight loss.

References

Capehorn MS, et al. "Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10)." Diabetes & Metabolism. 2020;46(2):100-109.
Rubino DM, et al. "Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial." JAMA. 2022;327(2):138-150.
Marso SP, et al. "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes." New England Journal of Medicine. 2016;375(4):311-322. (LEADER trial)
Marso SP, et al. "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes." New England Journal of Medicine. 2016;375(19):1834-1844. (SUSTAIN-6 trial)
Lau J, et al. "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide." Journal of Medicinal Chemistry. 2015;58(18):7370-7380.
Knudsen LB, Lau J. "The Discovery and Development of Liraglutide and Semaglutide." Frontiers in Endocrinology. 2019;10:155.
Shi Q, et al. "Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis." Frontiers in Pharmacology. 2025;16:1438318.
Alkhezi OS, et al. "Comparing the Efficacy of Liraglutide and Semaglutide on Weight Loss: Experience from the Middle East Gulf Region and Literature Review." Pharmaceuticals. 2025.
U.S. Food and Drug Administration. Ozempic (semaglutide) prescribing information. Revised 2024.
U.S. Food and Drug Administration. Victoza (liraglutide) prescribing information. Revised 2024.

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