The STEP 8 trial published in JAMA in January 2022 is the only direct head-to-head obesity comparison of these two GLP-1 drugs. Semaglutide 2.4 mg weekly produced 15.8 percent average weight loss over 68 weeks. Liraglutide 3.0 mg daily produced 6.4 percent. The gap is 9.4 percentage points, and the discontinuation rate was twice as high on liraglutide (27.6 percent vs 13.5 percent) despite similar GI side-effect frequencies. In 2026, generic Saxenda is finally on the US market at around $469 to $704 per pack, but semaglutide still wins on raw weight loss. Here is the complete data and who each drug actually fits.
If you want semaglutide at compounded cash price, Yucca Health prescribes it from $146 to $258 per month with US providers and 2-day shipping. The branded vs generic vs compounded comparison breakdown sits below.
🔑 Key Takeaways
- Semaglutide produces 2.5 times more weight loss in head-to-head STEP 8 trial (15.8 percent vs 6.4 percent at 68 weeks).
- Liraglutide had twice the dropout rate (27.6 percent vs 13.5 percent), despite nearly identical GI side-effect rates. Daily-injection burden drives most of the gap.
- Generic Saxenda launched August 2025 (Teva). Generic Victoza launched June 2024 (Teva) and December 2024 (Hikma). This is the first time generic GLP-1 weight loss drugs are available in the US.
- Liraglutide still wins for specific use cases: patients planning surgery or pregnancy (faster clearance), adolescents (longer pediatric track record), and patients who want generic-level pricing today.
- Semaglutide is the only GLP-1 with SELECT data (20 percent reduction in major cardiovascular events in non-diabetic obese adults, n=17,604). For cardiac risk reduction in obesity, semaglutide is the only labeled option.
Telehealth Comparison Table
The Head-to-Head Verdict in 30 Seconds
STEP 8 randomized 338 adults with overweight or obesity without diabetes to either semaglutide 2.4 mg weekly, liraglutide 3.0 mg daily, or placebo, with diet and activity counseling on top. After 68 weeks of treatment, the weight loss numbers were unambiguous.
| Outcome at 68 weeks | Semaglutide 2.4 mg | Liraglutide 3.0 mg |
|---|---|---|
| Mean body weight change | -15.8% | -6.4% |
| ≥10% weight loss | 70.9% | 25.6% |
| ≥15% weight loss | 55.6% | 12.0% |
| ≥20% weight loss | 38.5% | 6.0% |
| Discontinuation for AE | 13.5% | 27.6% |
The discontinuation gap is the more interesting finding. Both arms had similar GI side-effect rates (any GI AE: 84.1 percent semaglutide vs 82.7 percent liraglutide). But twice as many liraglutide patients quit. The authors attribute this to the daily-injection burden and the sharper PK profile of liraglutide, which produces more abrupt peaks and troughs of GLP-1 receptor occupancy.
SUSTAIN-10: When the Goal Is Diabetes, Not Weight
SUSTAIN-10 was the head-to-head trial in 577 adults with type 2 diabetes on 1 to 3 oral antidiabetics, comparing semaglutide 1.0 mg weekly vs liraglutide 1.2 mg daily over 30 weeks. The baseline characteristics: A1C 8.2, weight 96.9 kg.
| Outcome at 30 weeks | Semaglutide 1.0 mg | Liraglutide 1.2 mg |
|---|---|---|
| A1C reduction | -1.7% | -1.0% |
| Weight loss | -5.8 kg | -1.9 kg |
| A1C below 7% without hypoglycemia | 76% | 37% |
Even at the lower 1.0 mg semaglutide dose used for diabetes (vs the 2.4 mg dose used for weight loss), semaglutide outperformed the 1.2 mg liraglutide diabetes dose on every endpoint. This is the trial that shifted prescribing patterns in endocrinology away from liraglutide and toward semaglutide for new T2D starts.
How They're Built Differently: Pharmacology Side-by-Side
| Property | Liraglutide | Semaglutide |
|---|---|---|
| Backbone | Human GLP-1(7-37) with Arg34Lys, lipid at Lys26 | Human GLP-1(7-37) with Aib at position 2, Arg34Lys, lipid at Lys26 |
| Fatty-acid chain | C16 palmitic acid via glutamate spacer | C18 octadecanedioic acid via gamma-glutamate plus 2x mini-PEG spacer |
| DPP-4 resistance | No Aib substitution, faster proteolytic cleavage | Aib at position 2 blocks DPP-4 cleavage |
| Albumin binding | Strong | Stronger (longer fatty-diacid + linker) |
| Half-life | ~13 hours | ~165 hours (~7 days) |
| Dose frequency | Daily SC injection | Weekly SC injection |
| Steady state | ~3 days | ~4 to 5 weeks |
| Receptor affinity | Roughly comparable to native GLP-1 | Higher affinity, slower off-rate, longer signaling |
The structural difference that matters most is the Aib substitution at position 2 of semaglutide, which blocks the enzyme DPP-4 from cleaving the peptide. Combined with the longer fatty-acid chain that allows tighter albumin tethering, this drives the 12-fold longer half-life. The flatter PK curve produces more uniform receptor occupancy throughout the dosing interval, which translates to better appetite suppression and likely explains both the superior weight loss and the lower discontinuation rate.
FDA Approvals and Branded Products
Liraglutide
- Victoza (1.2 / 1.8 mg) FDA approved 2010 for T2D
- Saxenda (3.0 mg) FDA approved December 2014 for chronic weight management
- Saxenda pediatric FDA approved December 2020 for adolescents 12 to 17, the first GLP-1 approved for adolescent obesity
- Generic Victoza: Teva launched June 2024, Hikma followed December 2024 (~30 percent off branded)
- Generic Saxenda: Teva launched August 2025, the first generic GLP-1 indicated for weight loss
Semaglutide
- Ozempic (0.25 / 0.5 / 1.0 / 2.0 mg) FDA approved December 2017 for T2D
- Rybelsus (3 / 7 / 14 mg oral tablets) FDA approved September 2019 for oral T2D, first oral GLP-1
- Wegovy injectable (up to 2.4 mg) FDA approved June 2021 for chronic weight management
- Wegovy pediatric FDA approved December 2022 for ages 12 and up
- Wegovy oral 25 mg approved 2025 for chronic weight management
- SELECT label expansion March 2024: Wegovy approved to reduce MACE in non-diabetic obese adults with CVD
- No generic semaglutide available in US, patents extend into early 2030s
2026 Cost Comparison
| Product | Cash list / sticker | Cash program / best price |
|---|---|---|
| Saxenda 3.0 mg (branded) | $1,350 to $1,656/mo | Limited NovoCare programs |
| Generic Saxenda (Teva) | ~$945 to $1,300/mo | ~30% off branded |
| Victoza 1.8 mg (branded) | ~$900 to $1,000/mo | Limited programs |
| Generic Victoza (Teva / Hikma) | $469 to $704/pack | Cheaper at larger pack sizes |
| Wegovy 2.4 mg | $1,350 list | $199 first 2 months, $349/mo ongoing (NovoCare) |
| Wegovy + savings card + commercial insurance | n/a | $0 to $25/mo |
| Ozempic 1.0 mg | ~$998 list | $199 intro (2 mo), $349 to $499 ongoing |
| Rybelsus 14 mg | ~$1,000 to $1,350/mo | $149 to $299 pill program |
| Yucca compounded semaglutide | $146 to $258/mo | 6-month plan cheapest |
| MEDVi compounded semaglutide | $179 first / $299 refill | 4.4/5 Trustpilot |
The big shift in 2025 to 2026: generic liraglutide cracked the $500 floor for the first time. Compounded semaglutide via Yucca sits at $146 per month on the 6-month plan. NovoCare's $349 cash price for Wegovy closed most of the branded gap. The cheapest legitimate semaglutide path is still compounded; the cheapest legitimate liraglutide is generic Saxenda.
Side Effects Head-to-Head
| Event (STEP 8 trial) | Semaglutide 2.4 mg | Liraglutide 3.0 mg |
|---|---|---|
| Any GI AE | 84.1% | 82.7% |
| Nausea | 58% | 56% |
| Diarrhea | 33% | 25% |
| Constipation | 27% | 14% |
| Vomiting | 25% | 17% |
| Discontinuation for AE | 13.5% | 27.6% |
Class-level safety signals are similar for both: gallbladder events elevated (1 to 2 percent absolute risk in trials), rare acute pancreatitis, boxed warning for thyroid C-cell tumors derived from rodent studies, modest heart-rate increase (2 to 4 bpm). Injection-site reactions are more common with liraglutide simply because there are 7x as many injections per week.
Cardiovascular Outcomes: LEADER vs SELECT
Both drugs have cardiovascular outcomes data, but only one is FDA-labeled for cardiac risk reduction in non-diabetic obesity.
LEADER (liraglutide, n=9,340, 3.8-year median follow-up): 13 percent reduction in major adverse cardiovascular events in adults with T2D and high CV risk. This was the first GLP-1 RA to demonstrate cardiovascular benefit in T2D and is the basis of Victoza's CV indication.
SELECT (semaglutide, n=17,604, 208 weeks): 20 percent reduction in MACE in non-diabetic adults with obesity and established cardiovascular disease. This trial expanded semaglutide's label in March 2024 to cover MACE reduction in non-diabetic obese adults, the first GLP-1 to get this indication outside of diabetes.
If you have established CVD without diabetes and want labeled cardiac protection, semaglutide is the only option. If you have T2D and want strong outcomes data, both work but the trial-based reductions favor semaglutide.
Decision Framework: Who Fits Which
Pick liraglutide when:
- Daily injection routine is fine, weekly "stack" of side effects on semaglutide feels too spiky
- Surgery, pregnancy planning, or contrast imaging is on the horizon (liraglutide clears in ~3 days vs semaglutide's ~5 weeks)
- Cost matters and generic Saxenda is cheaper than NovoCare Wegovy in your market
- Adolescents 12 to 17 (Saxenda has the longer pediatric track record, though Wegovy is now approved too)
- T2D with cardio-renal protection needs and you want LEADER trial backing
Pick semaglutide when:
- Maximum weight loss is the goal (2.5 times more in STEP 8)
- Weekly injection works better for your routine than daily
- You have established CVD without diabetes (SELECT trial, only semaglutide is FDA-labeled for this)
- T2D with broader cardio-renal protection
- You want a future on-ramp to oral (Rybelsus tablet, Wegovy oral)
