Liraglutide vs Semaglutide: Two Generations of GLP-1

Are they the same kind of drug?

Both are GLP-1 receptor agonists from Novo Nordisk, and both slow gastric emptying [3][4]. They differ mainly in how long they last in the body. Liraglutide is an acylated human GLP-1 analogue with 97% sequence homology to endogenous GLP-1 and a plasma half-life of about 13 hours after a subcutaneous injection [3]. Semaglutide has 94% homology and an elimination half-life of about 1 week; the label states the drug remains in the body for roughly 5 to 7 weeks after the last 2.4 mg or 7.2 mg injection [4].

Liraglutide is sold as two brands: Saxenda, approved in December 2014 for weight management, and Victoza, approved in January 2010 for type 2 diabetes. Both are once-daily injections [3]. Victoza tops out at 1.8 mg daily and is not approved for weight loss [9]; Saxenda's recommended adult dose is 3 mg daily [3].

Semaglutide's US approvals include Ozempic injection in December 2017, Rybelsus tablets in September 2019, Wegovy injection in June 2021 and Wegovy tablets in December 2025 [8][10][11][12]. Ozempic has no weight-loss indication [13]. Wegovy injection is approved for weight management, cardiovascular risk reduction in eligible adults, and treatment of noncirrhotic MASH with moderate to advanced fibrosis [4]. Wegovy tablets are approved for weight management and cardiovascular risk reduction in adults, but not for MASH [4].

Which one produces more weight loss?

The SCALE Obesity trial randomized 3,731 adults without diabetes to liraglutide 3 mg daily or placebo for 56 weeks, both with lifestyle counseling [2]. The published results were a mean loss of 8.4 kg with liraglutide against 2.8 kg with placebo, and 63.2% versus 27.1% losing at least 5% of body weight [2]. The Saxenda label reports the same trial with a different imputation method: -7.4% versus -3.0% of body weight, 62.3% versus 34.4% losing 5% or more, and 33.9% versus 15.4% losing more than 10% [3].

STEP 1 randomized 1,961 adults without diabetes to semaglutide 2.4 mg weekly or placebo for 68 weeks [1]. Mean weight change was -14.9% versus -2.4%, with 86.4% versus 31.5% losing 5% or more, 69.1% versus 12.0% losing 10% or more, and 50.5% versus 4.9% losing 15% or more [1].

These two sets of figures come from separate trials that differ in length, in the populations recruited and in how missing data were handled, so the gap between them is not a head-to-head measurement.

Weight loss was smaller for both drugs in trials of adults with type 2 diabetes [14][15]. In SCALE Diabetes (846 adults), the Saxenda label reports 5.4% versus 1.7% mean weight loss for liraglutide 3 mg versus placebo, and 49% versus 16.4% lost 5% or more [3]; the published trial reports 6.0% versus 2.0% [14]. In STEP 2 (1,210 adults with type 2 diabetes), semaglutide 2.4 mg produced -9.6% versus -3.4%, with 68.8% versus 28.5% losing 5% or more [15].

How do the side effects compare?

The Saxenda label pools five placebo-controlled adult trials: 3,384 people on liraglutide and 1,941 on placebo, treated for up to 56 weeks [3]. Nausea occurred in 39.3% versus 13.8%, diarrhea in 20.9% versus 9.9%, constipation in 19.4% versus 8.5% and vomiting in 15.7% versus 3.9% [3]. Treatment was stopped for an adverse reaction by 9.8% versus 4.3% [3].

The Wegovy label pools three placebo-controlled trials in adults with obesity or overweight, up to 68 weeks: 2,116 on semaglutide 2.4 mg and 1,261 on placebo [4]. Nausea occurred in 44% versus 16%, diarrhea in 30% versus 16%, vomiting in 24% versus 6% and constipation in 24% versus 11%; 6.8% versus 3.2% stopped for adverse reactions [4]. Those figures come from separate programs, and the Saxenda label itself cautions that adverse reaction rates from different clinical trials cannot be directly compared [3].

Both labels carry the same boxed warning: in rodents the drugs cause thyroid C-cell tumors at clinically relevant exposures, the human relevance is unknown, and both are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2 [3][4]. Both warn about pancreatitis, gallbladder disease, hypoglycemia when combined with insulin or a sulfonylurea, kidney injury from dehydration, severe gastrointestinal reactions, and pulmonary aspiration during general anesthesia or deep sedation; neither is recommended in severe gastroparesis [3][4].

Both weight-management labels once carried a suicidal behavior and ideation warning. FDA asked the manufacturers on 13 January 2026 to remove it after a review that found no increased risk, and the current Saxenda and Wegovy labels no longer contain it [16][3][4].

Do they reduce heart attacks and strokes?

LEADER randomized 9,340 adults with type 2 diabetes and high cardiovascular risk to liraglutide (1.8 mg target dose) or placebo for a median 3.8 years [5]. The composite of cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 13.0% versus 14.9% (hazard ratio 0.87, 95% CI 0.78 to 0.97), and cardiovascular death in 4.7% versus 6.0% [5].

SUSTAIN-6 randomized 3,297 adults with type 2 diabetes to semaglutide 0.5 or 1 mg or placebo for 104 weeks; the same composite occurred in 6.6% versus 8.9% (hazard ratio 0.74, 0.58 to 0.95) [17].

SELECT tested semaglutide in a different population: 17,604 adults with established cardiovascular disease and a BMI of 27 or more but no diabetes [6]. Over a mean 39.8 months the composite occurred in 6.5% versus 8.0% (hazard ratio 0.80, 0.72 to 0.90) [6]. Cardiovascular death alone was 2.5% versus 3.0% (hazard ratio 0.85, 0.71 to 1.01), and superiority for that component was not confirmed in the prespecified testing hierarchy [6][4].

How is each one dosed?

Saxenda starts at 0.6 mg once daily for one week and rises weekly (1.2, 1.8, 2.4, then 3 mg from week 5) [3]. The label says to evaluate weight at 16 weeks and to stop if less than 4% of baseline weight has been lost [3]. For missed doses, the label says to restart at 0.6 mg and re-titrate if more than three days have passed since the last dose [3].

Wegovy injection starts at 0.25 mg weekly for four weeks and steps up every four weeks (0.5, 1, 1.7 mg) to a maintenance dose of 2.4 mg from week 17; adults who tolerate 2.4 mg for at least four weeks and need more weight loss may go to a maximum of 7.2 mg weekly [4]. The label says a missed weekly dose is given if the next scheduled dose is more than two days away [4]. Liraglutide is available only as an injection, while semaglutide also comes as a tablet whose oral bioavailability is about 1% to 2% against 89% for the injection, so tablet and injection doses in mg are not interchangeable [3][4].

What happens when you stop?

STEP 4 took 803 adults who had lost a mean 10.6% over a 20-week run-in and randomized them to continue semaglutide 2.4 mg or switch to placebo for 48 weeks [18]. Weight changed by -7.9% in those who continued and +6.9% in those switched to placebo [18].

In the STEP 1 off-treatment extension of 327 participants, weight loss at week 68 was 17.3% with semaglutide versus 2.0% with placebo; a year after stopping, semaglutide participants had regained 11.6 percentage points, for a net loss of 5.6% from baseline [19]. In the adolescent liraglutide trial of 251 participants aged 12 to under 18, weight regain after stopping was greater with liraglutide than with placebo [20].

Generic liraglutide and compounded semaglutide

FDA-approved generic liraglutide exists, with approvals referencing both Saxenda for weight management and Victoza for type 2 diabetes [7]. The approved semaglutide products are Novo Nordisk brands [8][10][11][12].

FDA says compounded drugs are not FDA approved and are not reviewed for safety, effectiveness or quality before marketing, and the agency had received 990 adverse event reports for compounded semaglutide as of 31 May 2026 [21]. On 30 April 2026 FDA proposed excluding semaglutide, tirzepatide and liraglutide from the list of bulk substances outsourcing facilities may compound with, finding no clinical need; comments were due 29 June 2026 and no final decision had been made [22].