Liraglutide vs Semaglutide: differences, evidence and safety

Answer first

Liraglutide and semaglutide both copy the gut hormone GLP-1, come from the same company and are prescription medicines. Semaglutide lasts about a week in the body, liraglutide about 13 hours. In STEP 8, the only head-to-head trial found, 338 adults with obesity but no diabetes lost 15.8% of their weight on semaglutide and 6.4% on liraglutide over 68 weeks.

At a glance

How they work

Both are peptides of 31 building blocks, made in the laboratory by Novo Nordisk. Both are altered copies of the human gut hormone GLP-1 and switch on its docking point, the GLP-1 receptor ^[1], ^[2].

Liraglutide

• Close to the natural hormone. It matches GLP-1 in 97% of its sequence. It is brewed in baker's yeast before a fatty tail is attached ^[1].
• Insulin only when needed. Insulin is released only while blood sugar is actually high. Less glucagon, the hormone that pushes blood sugar up, is released ^[1].
• Stomach and appetite. The stomach empties more slowly. The European text attributes the effect on weight to appetite and fullness signals in the brain ^[1], ^[3].
• Duration. A 16-carbon fatty chain sticks it to a carrier protein in the blood. The body clears half of it in about 13 hours ^[1].

Semaglutide

• One docking point only. It matches GLP-1 in 94% of its sequence and leaves the docking points of related gut hormones alone ^[2].
• Insulin and glucagon. More insulin and less glucagon are released, both only when blood sugar is high. The stomach empties a little more slowly after a meal ^[2].
• Protected against breakdown. One building block is swapped so that the enzyme which normally cuts GLP-1 apart within minutes cannot get a grip ^[4].
• Duration. A long fatty chain holds it to a carrier protein for about a week. It is still detectable roughly 5 weeks after the last dose ^[2].

The core difference is the fatty chain and what follows from it. Semaglutide's longer chain holds it in the body for days rather than hours ^[1], ^[2]. Semaglutide also exists as a tablet, which contains an extra ingredient that helps the peptide cross the wall of the stomach ^[5].

What the studies show

The head-to-head trial

Phase 3b RCT, the drug comparison unblinded STEP 8 put the two substances side by side in 338 adults with obesity and without diabetes, over 68 weeks at 19 American centres. Each drug was blinded against its own dummy treatment, but participants knew which of the two drugs they were on ^[6]. No other study comparing the two directly could be found in the sources reviewed for this page.

Weight fell by 15.8% on semaglutide against 6.4% on liraglutide, a gap of 9.4 percentage points (range 6.8 to 12.0, p < 0.001). On the dummy treatment it fell by 1.9% ^[6].

A loss of at least a tenth of body weight was reached by 70.9% on semaglutide against 25.6% on liraglutide. A loss of at least a fifth was reached by 38.5% against 6.0% ^[6].

Twice as many people stopped treatment on liraglutide, 27.6% against 13.5% ^[6]. Its limits are plain: it enrolled 338 people at 19 centres, and everyone knew which drug they were taking ^[6].

Everything below comes from separate trials. They enrolled different people, over different lengths of time, and measured different endpoints. Their numbers cannot be set against each other.

Weight in adults without diabetes

Phase 3 RCT SCALE enrolled 3,731 adults with obesity, or excess weight plus a related condition, and without diabetes. After 56 weeks the liraglutide group had lost 8.4 kg on average against 2.8 kg on placebo ^[7]. The American labelling reports the same trial as a fall of 7.4% against 3.0% ^[8].

Phase 3 RCT STEP 1 enrolled 1,961 adults with obesity and without diabetes. After 68 weeks the semaglutide group had lost 14.9% of their weight against 2.4% on placebo, a gap of 12.4 percentage points ^[9].

Weight in adults with type 2 diabetes

Phase 3 RCT SCALE Diabetes enrolled 846 adults with type 2 diabetes. Over 56 weeks weight fell by 6.0% at the higher liraglutide dose level and 4.7% at the lower one, against 2.0% on placebo ^[10].

Phase 3 RCT STEP 2 enrolled 1,210 adults with type 2 diabetes. Weight fell by 9.6% on semaglutide against 3.4% on placebo ^[11]. In both drugs the effect was smaller in people with diabetes than without ^[10], ^[11].

Keeping the weight off

Phase 3 RCT, maintenance design SCALE Maintenance took 422 adults who had already lost at least a twentieth of their weight on a low-calorie diet. Over the next 56 weeks the liraglutide group lost a further 6.2% against 0.2% ^[12]. The American labelling states that this result does not carry over to the general population ^[8].

Phase 3 RCT, withdrawal design In STEP 4, 803 adults were first treated with semaglutide for 20 weeks. Between week 20 and week 68, those who carried on lost a further 7.9%, while those switched to placebo put 6.9% back on ^[13].

Heart

Phase 3 RCT LEADER enrolled 9,340 adults with type 2 diabetes and a high heart risk, followed for a median of 3.8 years. A serious heart event struck 13.0% on liraglutide against 14.9% on placebo (hazard ratio 0.87, range 0.78 to 0.97, p = 0.01) ^[14].

Counted separately, heart attacks and strokes showed no clear difference. For heart attacks that people survived, the hazard ratio was 0.88 (range 0.75 to 1.03), for strokes 0.89 (range 0.72 to 1.11) ^[14].

Phase 3 RCT, built only to show it was no worse SUSTAIN-6 followed 3,297 adults with type 2 diabetes and a high heart risk. Over 104 weeks a serious heart event struck 6.6% on semaglutide against 8.9% on placebo (hazard ratio 0.74, range 0.58 to 0.95) ^[15].

Phase 3 RCT SELECT enrolled 17,604 adults aged 45 and over with obesity and existing heart disease, but without diabetes. Over a median of 39.8 months a serious heart event struck 6.5% on semaglutide against 8.0% (hazard ratio 0.80, range 0.72 to 0.90) ^[16].

For liraglutide, no long-term heart trial in people with obesity but without diabetes could be found in the sources reviewed. LEADER was run in people with diabetes ^[14].

Teenagers

Phase 3 RCT SCALE Teens enrolled 251 young people aged 12 to 17 with obesity for 56 weeks. The body mass index score fell by 0.22 points more on liraglutide than on placebo (range 0.08 to 0.37, p = 0.002). After the drug stopped, the score climbed back faster in the treated group ^[17].

Phase 3 RCT STEP TEENS enrolled 201 young people aged between 12 and 18. Body mass index fell by 16.1% on semaglutide against a rise of 0.6% on placebo ^[18].

The two trials used different measures, a score in one and a percentage change in the other.

Outcomes reported here for one substance only

• Liraglutide and later diabetes. The trial followed 2,254 adults with raised blood sugar. By week 160, type 2 diabetes was diagnosed in 2% on liraglutide against 6% on placebo (hazard ratio 0.21, range 0.13 to 0.34). Only 1,128 reached week 160 ^[19].
• Semaglutide and the kidneys. FLOW enrolled 3,533 adults with type 2 diabetes and long-standing kidney disease. The main kidney outcome occurred 331 times against 410 (hazard ratio 0.76, range 0.66 to 0.88) ^[20].
• Semaglutide and the liver. ESSENCE enrolled people with an inflamed fatty liver and moderate to advanced scarring. In its first 800 participants, liver inflammation cleared without worse scarring in 62.9% against 34.3% by week 72. The result is an interim look ^[21].
• Semaglutide and Alzheimer's disease. Two trials in 3,808 people with early Alzheimer's disease failed on their main question about thinking and memory. The differences from placebo were −0.08 (p = 0.57) and 0.10 (p = 0.46) ^[22].

Safety

Both drugs share the same main complaints: feeling sick, diarrhoea, constipation and vomiting. The figures below come from each drug's own pooled weight trials in adults, as printed in the American labelling. They cover different trials and are not a ranking.

Liraglutide. The pooled trials covered 3,384 people on the drug against 1,941 on placebo ^[8].

• Stomach and bowel. Feeling sick affected 39.3% against 13.8%, diarrhoea 20.9% against 9.9%, constipation 19.4% against 8.5% and vomiting 15.7% against 3.9%. Any such complaint affected 68% against 39% ^[8].
• Pancreas. Sudden inflammation of the pancreas was confirmed in 9 people of 3,291 against 2 of 1,843 ^[8].
• Gallbladder. Gallstones occurred in 2.2% against 0.8% ^[8].
• Pulse. The resting heart rate rose by 2 to 3 beats a minute on average. A rise of more than 10 beats at two visits in a row occurred in 34% against 19% ^[8].
• Teenagers. Feeling sick affected 42.4% against 14.3%, and vomiting 34.4% against 4% ^[8].

Semaglutide. The pooled trials covered 2,116 people on the drug against 1,261 on placebo ^[4].

• Stomach and bowel. Feeling sick affected 44% against 16%, diarrhoea 30% against 16%, vomiting 24% against 6% and constipation 24% against 11%. Any such complaint affected 73% against 47%, and severe complaints 4.1% against 0.9% ^[4].
• Pancreas. There were 4 confirmed cases against 1 ^[4].
• Gallbladder. Gallstones occurred in 1.6% against 0.7% ^[4].
• Diabetic eye disease. In the SUSTAIN-6 trial, retinal complications occurred in 3.0% against 1.8% (hazard ratio 1.76, range 1.11 to 2.78) ^[15].
• Stopping. In SELECT, 16.6% stopped because of side effects, against 8.2% on placebo ^[16].

Shared warnings. The American package inserts of both drugs carry a boxed warning. In rats and mice, both cause tumours of the C-cells of the thyroid gland, more often at higher amounts and longer exposure. Whether this applies to people is unknown ^[1], ^[4].

Neither may be used by anyone who has had medullary thyroid cancer or has it in the family. The same applies to a particular inherited hormone syndrome. The European liraglutide texts carry no boxed warning and name only allergy as a bar ^[1], ^[23].

On 29 January 2026 the British regulator tightened the pancreatitis warning for the whole class and named both substances ^[24]. Both labels warn that a pen holding several doses must not be passed between people, even with a fresh needle ^[1], ^[4].

Sudden loss of vision. In June 2025 the European committee added damage to the optic nerve (non-arteritic anterior ischaemic optic neuropathy) to the semaglutide texts. It counts as a very rare side effect, meaning up to 1 in 10,000 people treated ^[25], ^[26].

The British regulator's update of 5 February 2026 states that other drugs of the class were not included in its review. Nothing about liraglutide follows from that either way ^[27].

Why this page lists no doses. Both drugs are prescription-only wherever they are approved. Choosing an amount is a matter for the product information and the prescribing doctor. This page therefore names dose levels only as lower or higher, never as an amount.

Legal status

Liraglutide is an approved, prescription-only medicine in seven markets. Europe authorised it on 30 June 2009 and the United States on 25 January 2010. The first American generic version was approved on 23 December 2024 ^[23], ^[28], ^[29]. Semaglutide is approved and prescription-only in eight markets. The United States cleared it on 5 December 2017, the European Union on 8 February 2018 ^[30], ^[26]. Neither is on the 2026 prohibited list of the World Anti-Doping Agency. Semaglutide sits in section 6 of the penalty-free monitoring programme, liraglutide does not ^[31], ^[32]. The monographs reflect the position on 10 September 2026 for liraglutide and 6 September 2026 for semaglutide.

Used together?

The myPeptides blend directory lists no product that combines liraglutide and semaglutide. Its only entry containing semaglutide, Cagrilintide + Semaglutide, pairs it with cagrilintide, a copy of the appetite hormone amylin. The directory describes that combination as studied in trials but not approved.

No study of liraglutide and semaglutide given together could be found in the sources reviewed for this page. STEP 8 involved both, but it set one against the other rather than combining them ^[6]. Both act on the same receptor, and the American liraglutide labelling advises against combining several products of this kind ^[1], ^[8].

Frequently asked questions

Which is better, liraglutide or semaglutide?

None of the trials found answers that in general. STEP 8 compared them for one measure, body weight, in one group. It enrolled 338 adults with obesity and without diabetes. Over 68 weeks, weight fell by 15.8% on semaglutide and by 6.4% on liraglutide. No head-to-head trial of heart, kidney or blood sugar outcomes could be found in the sources reviewed for this page.

Is liraglutide or semaglutide safer?

No trial built to compare their safety could be found in the sources reviewed for this page. In STEP 8, 27.6% stopped liraglutide and 13.5% stopped semaglutide. Both labels list the same kinds of warnings, including inflammation of the pancreas and gallbladder trouble. Their side-effect rates come from separate pooled trials and cannot be ranked.

What is the difference between liraglutide and semaglutide?

Both switch on the GLP-1 receptor and both are made by Novo Nordisk. Semaglutide carries a longer fatty chain, lasts about a week instead of about 13 hours, and also comes as a tablet. Semaglutide has large trials on the heart without diabetes, the kidneys and the liver; liraglutide has a heart trial in type 2 diabetes.

Can liraglutide and semaglutide be taken together?

No study of the two given together could be found in the sources reviewed for this page. The myPeptides blend directory lists no product that combines them. Both act on the same receptor. The American liraglutide labelling advises against combining several products of this kind.

Is liraglutide the same as semaglutide?

No. Both are altered copies of the same gut hormone from the same company, but they are separate substances with separate approvals. Liraglutide matches the natural hormone in 97% of its sequence, semaglutide in 94%.

How long do liraglutide and semaglutide stay in the body?

The body clears half of a liraglutide dose in about 13 hours. For semaglutide that takes about a week, and it is still detectable roughly 5 weeks after the last dose. In both, a fatty chain makes the peptide stick to a carrier protein in the blood.

Have liraglutide and semaglutide been shown to lower heart risk?

Each in its own trial. In LEADER, among 9,340 adults with type 2 diabetes, serious heart events struck 13.0% on liraglutide against 14.9% on placebo. In SELECT, among 17,604 adults with obesity and heart disease but no diabetes, they struck 6.5% on semaglutide against 8.0% on placebo. The two trials enrolled different people and cannot be compared.

Are liraglutide and semaglutide banned in sport?

Neither is on the 2026 prohibited list of the World Anti-Doping Agency, in or out of competition. Semaglutide sits in the monitoring programme, which carries no penalty. Liraglutide is not named in that programme.