Liraglutide and semaglutide are close relatives: both are modified copies of GLP-1, a hormone the gut releases after a meal, and both are approved for long-term weight management as injections. The practical difference most people notice first is the calendar, one shot a day against one a week, and that difference turns out to explain a good deal of how the two drugs are dosed.
The comparison is unusually clean, because the two were tested against each other in a 68-week weight trial. The newer weekly drug is also compared with tirzepatide in tirzepatide vs semaglutide.
Two ways of making a short-lived hormone last
Natural GLP-1 barely survives in the blood: the Saxenda label gives its half-life as 1.5 to 2 minutes, because enzymes called DPP-4 and neutral endopeptidases break it down almost as soon as it is released [1]. Any drug built on it has to solve that problem first.
Liraglutide shares 97% of its amino acid sequence with human GLP-1 [1]. Its label explains the longer life as a combination of three things: the molecules clump together under the skin, which slows absorption; it binds to proteins in the blood; and it resists those two enzymes. The result is a plasma half-life of about 13 hours, which is why it is injected every day.
Semaglutide shares 94% of the sequence [2]. Its main trick, according to its label, is a fatty side chain attached at position 26 that makes it bind tightly to albumin, a carrier protein in the blood, plus a change at position 8 that protects it from DPP-4. Its elimination half-life is about 1 week, and the label notes it stays in circulation for about 5 to 7 weeks after the last dose.
For someone taking either drug, the half-life shapes more than the injection day. The Saxenda label says that after more than 3 days without a dose, the climb restarts at 0.6 mg [1]. The Wegovy label cites semaglutide’s long half-life when it advises stopping at least 2 months before a planned pregnancy [2].
~13 h
liraglutide plasma half-life
Saxenda label
~1 week
semaglutide elimination half-life
Wegovy label
55% vs 89%
absolute bioavailability under the skin, liraglutide vs semaglutide
Saxenda and Wegovy labels
How each label steps up the dose
Saxenda starts at 0.6 mg a day and rises by 0.6 mg each week until it reaches 3 mg in week 5, the only maintenance dose for adults; the lower doses exist only to get there. [1] The label adds a checkpoint: if an adult has not lost at least 4% of starting weight after 16 weeks, it says to stop, because meaningful weight loss is then unlikely.
Wegovy starts at 0.25 mg once a week and climbs every 4 weeks, through 0.5, 1 and 1.7 mg, to a maintenance dose of 2.4 mg from week 17 [2]. The current label also allows a further step to 7.2 mg a week for adults who have tolerated 2.4 mg for at least 4 weeks and need more weight loss.
Neither label explains why one drug steps up weekly and the other monthly. A reasonable reading is the half-life: a weekly drug is still building up from earlier doses for several weeks, so each step needs longer to settle. That is an inference from the pharmacology, not a statement either label makes.
The head-to-head weight trial: STEP 8
STEP 8 randomized 338 adults with obesity, or overweight with a related condition, and no diabetes, at 19 US sites [3]. They received weekly semaglutide 2.4 mg, daily liraglutide 3.0 mg, or matching placebo for 68 weeks, all with diet and activity counseling.
Mean weight fell 15.8% on semaglutide and 6.4% on liraglutide, a difference of 9.4 percentage points in semaglutide’s favor (95% CI, 6.8 to 12.0) [3]. The pooled placebo groups lost 1.9%. Losing 15% or more of body weight happened for 55.6% of people on semaglutide and 12.0% on liraglutide.
The trial had limits that belong next to those numbers. The comparison between the two drugs was open-label, so participants knew which one they were on; 78.4% were women; and it ran for 68 weeks [3]. Both brands belong to the same maker, whose employees were among the trial’s authors, so it was not a contest between rival sponsors [1] [2].
−15.8%
mean weight change on semaglutide 2.4 mg at 68 weeks
STEP 8
−6.4%
mean weight change on liraglutide 3.0 mg at 68 weeks
STEP 8
70.9% vs 25.6%
lost 10% or more of body weight
STEP 8
Side effects side by side
In STEP 8, stomach and bowel side effects were reported by 84.1% of people on semaglutide and 82.7% on liraglutide, close to a tie [3]. More people stopped liraglutide for any reason, 27.6% against 13.5%, though the trial counted every reason for stopping, not only side effects.
The labels, which pool each drug’s own placebo-controlled trials, show a similar pattern. Nausea was reported by 39.3% on Saxenda against 13.8% on placebo [1], and by 44% on Wegovy 2.4 mg against 16% on placebo [2]. Stopping for side effects was 9.8% on Saxenda and 6.8% on Wegovy. Those figures come from different trials and cannot be compared directly.
In type 2 diabetes, at lower doses
SUSTAIN 10 compared the two drugs at their diabetes doses: semaglutide 1.0 mg weekly against liraglutide 1.2 mg daily, in 577 adults with type 2 diabetes for 30 weeks [4]. These are not the Wegovy or Saxenda doses.
HbA1c, the long-term blood sugar measure, fell 1.7 points on semaglutide and 1.0 on liraglutide, and weight fell 5.8 kg against 1.9 kg [4]. Here the direction of dropouts reversed: 11.4% stopped semaglutide for side effects, against 6.6% on liraglutide, and stomach side effects ran 43.9% against 38.3%.
What this means
On the evidence of the one trial that tested them against each other at weight-management doses, semaglutide took off more than twice as much weight as liraglutide, with a similar rate of stomach side effects. Its longer half-life is also what allows one injection a week in place of seven.
Semaglutide also comes as a daily tablet, covered in Wegovy pill, and the newest daily option is the orforglipron tablet, covered in Foundayo. The wider field is set out in peptides for weight loss, and the weight goal page is the place to start comparing options.