Peptide Evidence Index

Liraglutide

Evidence last reviewed: September 2026

Quick answers

What is it?: Liraglutide is a synthetic analog of human GLP-1, injected once daily, sold as Victoza for diabetes and Saxenda for weight management.
Why are people interested in it?: It was the first GLP-1 drug to show a cardiovascular benefit in a dedicated outcomes trial and meaningful weight loss in a dedicated obesity trial.
What has actually been studied?: Large randomized trials in adults with type 2 diabetes at high cardiovascular risk and in adults with obesity or prediabetes, plus the earlier LEAD program that supported its original approval.
How strong is the evidence?: Solid and long-standing, but its own placebo-controlled effects are consistently smaller than those later shown for semaglutide and tirzepatide in head-to-head evidence.
What don't we know yet?: What happens specifically after stopping liraglutide, since no dedicated withdrawal trial like STEP 1's extension has been run for it.
Where can I read the original research?: Sources at the bottom of this page: LEADER (Marso et al., NEJM 2016) and SCALE Obesity and Prediabetes (Pi-Sunyer et al., NEJM 2015).

Plain-English overview

Liraglutide is a synthetic analog of human GLP-1, about 97% identical to the native hormone's amino-acid sequence, with a fatty-acid side chain that binds albumin and extends its half-life to roughly 13 hours — short enough to require once-daily injection, unlike the once-weekly drugs that followed it. It was the first GLP-1 receptor agonist to demonstrate a cardiovascular benefit in a dedicated outcomes trial and the first approved specifically for weight management at a higher dose than its diabetes formulation. It is FDA-approved as Victoza for type 2 diabetes, with a cardiovascular-risk-reduction indication added in 2017, and as Saxenda for chronic weight management. It has since been largely superseded in practice by once-weekly successors — semaglutide and tirzepatide — that produced larger effects in head-to-head evidence, but its own trial record, including the LEAD program that supported its original diabetes approval, is substantial and long-standing.

What researchers are studying it for

Type 2 diabetes (glycemic control)
Cardiovascular risk reduction in type 2 diabetes
Chronic weight management in overweight/obesity

Current evidence level

Randomized trials

Regulatory status: Approved medicine. Evidence strength and approval are scored separately; approval is a regulatory decision about a specific use, not a measure of how much research exists.

Human research

LEADER (Marso et al., NEJM 2016) randomized 9,340 adults with type 2 diabetes and high cardiovascular risk to daily liraglutide or placebo, added to standard care; over a median 3.8 years, the composite of cardiovascular death, non-fatal heart attack, or non-fatal stroke occurred in 13.0% of the liraglutide group versus 14.9% with placebo, a statistically significant reduction that established the drug's cardiovascular-benefit indication. SCALE Obesity and Prediabetes (Pi-Sunyer et al., NEJM 2015) randomized 3,731 adults without diabetes, most with prediabetes, to daily liraglutide 3.0 mg or placebo for 56 weeks alongside lifestyle counseling; the liraglutide group lost a mean 8.4 kg versus 2.8 kg with placebo, and 63.2% lost at least 5% of body weight versus 27.1% on placebo. Before either of those, the LEAD program of trials established liraglutide's glucose-lowering effect in type 2 diabetes and supported its original approval; LEAD-6 (Buse et al., Lancet 2009) directly compared once-daily liraglutide against twice-daily exenatide over 26 weeks and found liraglutide produced significantly greater HbA1c reduction. 514 studies listing liraglutide as an intervention are registered on ClinicalTrials.gov, reflecting its longer market history relative to semaglutide and tirzepatide. What happens after stopping liraglutide has not been studied with the same dedicated withdrawal-trial design used for semaglutide's STEP 1 extension or tirzepatide's SURMOUNT-4; the general class pattern of weight regain is expected to apply but has not been directly measured for this drug.

Animal and preclinical research

As with the rest of this drug class, rodent studies found thyroid C-cell tumors, the basis for liraglutide's boxed warning and its contraindication in people with a personal or family history of medullary thyroid carcinoma or MEN2. The source material reviewed here does not describe other animal studies in detail.

Major findings

LEADER: 13% relative reduction in cardiovascular death, heart attack, or stroke over a median 3.8 years in 9,340 adults with type 2 diabetes at high cardiovascular risk.
SCALE: mean 8.4 kg weight loss over 56 weeks versus 2.8 kg with placebo, in 3,731 adults without diabetes.
LEAD-6: once-daily liraglutide produced significantly greater HbA1c reduction than twice-daily exenatide over 26 weeks.
514 studies registered on ClinicalTrials.gov, with hundreds posting results.
Liraglutide was the first GLP-1 drug to show a cardiovascular benefit in a dedicated outcomes trial.

What has not been established

What happens after stopping liraglutide specifically — no dedicated withdrawal trial exists comparable to STEP 1's extension or SURMOUNT-4.
Multi-decade safety — LEADER followed patients for a median 3.8 years, and SCALE's main phase ran 56 weeks.
Whether the rodent thyroid C-cell tumor signal applies to humans.
Cardiovascular benefit in lower-risk diabetes patients — LEADER enrolled people selected for elevated cardiovascular risk.

Important limitations

LEADER enrolled adults selected specifically for elevated cardiovascular risk, so its benefit does not automatically apply to lower-risk diabetes patients.
SCALE excluded people with a history of major depressive disorder or a suicide attempt, uncontrolled hypertension, and prior obesity surgery.
Head-to-head trials with newer drugs favor semaglutide and tirzepatide, so liraglutide's placebo-controlled record, while real, no longer represents the most effective drug in its class.
Requires once-daily injection with a daily escalation schedule, unlike the once-weekly drugs that followed it.

Regulatory status

Approved by the FDA as Victoza (subcutaneous, once daily) in January 2010 for type 2 diabetes, with an added cardiovascular-risk-reduction indication in 2017 based on LEADER; and as Saxenda (subcutaneous, once daily, 3.0 mg) in December 2014 for chronic weight management. Not on the World Anti-Doping Agency's Prohibited List.

Primary research sources

Marso SP et al., LEADER: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes: NEJM 2016; PMID 27295427; ClinicalTrials.gov NCT01179048
Pi-Sunyer X et al., SCALE Obesity and Prediabetes: NEJM 2015; PMID 26132939; ClinicalTrials.gov NCT01272219
Buse JB et al., LEAD-6: Liraglutide Once a Day versus Exenatide Twice a Day for Type 2 Diabetes: Lancet 2009; PMID 19515413

Full evidence entry (complete data, registry records, dosing evidence)

Approved medicine

Approved by a major regulator for a specific use

At a glance

Also known as: Victoza, Saxenda
Class: GLP-1 receptor agonist
Derived from: A synthetic analog of human GLP-1, about 97% identical to the native hormone's amino-acid sequence, with a fatty-acid side chain that binds albumin to extend its half-life to roughly 13 hours — short enough to require once-daily injection, unlike the once-weekly drugs that followed it
Registered human trials: 514
…with published results: hundreds, including every pivotal trial cited below (counted on ClinicalTrials.gov this session)
Largest human trial: 9,340 adults with type 2 diabetes and high cardiovascular risk (LEADER, 2016) — liraglutide reduced the composite of cardiovascular death, non-fatal heart attack, or non-fatal stroke by 13% versus placebo over a median 3.8 years
Studied for: type 2 diabetes (glycemic control), cardiovascular risk reduction in type 2 diabetes, chronic weight management in overweight/obesity
Dosing evidence: Prescribed by a clinicianEvery studied dose followed a supervised daily escalation schedule defined by the trial protocol and, in practice, by a prescriber following the FDA-approved label.
Regulatory status: Approved by the FDA as Victoza (subcutaneous, once daily) in January 2010 for type 2 diabetes, with an added cardiovascular-risk-reduction indication in 2017 based on LEADER; and as Saxenda (subcutaneous, once daily, 3.0 mg) in December 2014 for chronic weight management in adults, and later adolescents, with obesity or overweight plus a weight-related condition.
Anti-doping status: Not on the World Anti-Doping Agency's Prohibited List

What it is

Liraglutide is a synthetic analog of human GLP-1 — about 97% identical to the native hormone's amino-acid sequence, with a fatty-acid chain attached that lets it bind albumin in the blood. That extends its half-life to roughly 13 hours, which is why it is injected once daily, unlike the once-weekly semaglutide and tirzepatide that followed it. It was the first GLP-1 receptor agonist to demonstrate a cardiovascular benefit in a dedicated outcomes trial, and the first approved specifically for weight management at a higher dose than its diabetes formulation.

It is FDA-approved as Victoza for type 2 diabetes, with a cardiovascular-risk-reduction indication added in 2017, and as Saxenda, at a higher daily dose, for chronic weight management.

What the studies actually found

LEADER (Marso et al., NEJM 2016; PubMed PMID 27295427, DOI) randomized 9,340 adults with type 2 diabetes and high cardiovascular risk to daily liraglutide or placebo, added to standard care. Over a median 3.8 years, the composite of cardiovascular death, non-fatal heart attack, or non-fatal stroke occurred in 13.0% of the liraglutide group versus 14.9% with placebo (hazard ratio 0.87) — a statistically significant reduction that established the drug's cardiovascular-benefit indication.

SCALE Obesity and Prediabetes (Pi-Sunyer et al., NEJM 2015; PubMed PMID 26132939, DOI) randomized 3,731 adults without diabetes, most with prediabetes, to daily liraglutide 3.0 mg or placebo for 56 weeks alongside lifestyle counseling. The liraglutide group lost a mean 8.4 kg versus 2.8 kg with placebo; 63.2% lost at least 5% of body weight versus 27.1% on placebo.

What exists in humans

514 studies listing liraglutide as an intervention are registered on ClinicalTrials.gov as of this session — a reflection of its longer market history relative to semaglutide and tirzepatide. Both pivotal trials above posted full results in peer-reviewed journals.

LEADER enrolled adults selected specifically for elevated cardiovascular risk, either existing cardiovascular disease or multiple risk factors; its benefit does not automatically apply to lower-risk diabetes patients. SCALE excluded people with a history of major depressive disorder or a suicide attempt, uncontrolled hypertension, and prior obesity surgery, and — as with the rest of this drug class — anyone with a personal or family history of medullary thyroid carcinoma or MEN2.

What doses have been studied in humans

LEADER gave 9,340 adults with type 2 diabetes a once-daily subcutaneous injection, escalated to a target maintenance dose over several weeks and continued for a median 3.8 years; the endpoint was time to a cardiovascular event. SCALE gave 3,731 adults without diabetes a once-daily subcutaneous injection escalated over five weeks to a 3.0 mg maintenance dose, continued for 56 weeks; the endpoint was percent change in body weight.

As with all drugs in this class, the specific dose, escalation schedule, and target maintenance level for a given patient are set by a prescriber against the FDA-approved label for that patient's indication — diabetes and weight management use different maintenance doses of the same molecule — not by extrapolating from a trial protocol. Nothing here describes what a reader should take.

What remains unknown

What happens after stopping has not been studied for liraglutide with the same dedicated withdrawal-trial design used for semaglutide's STEP 1 extension or tirzepatide's SURMOUNT-4. The general GLP-1 class pattern — substantial weight regain within a year of discontinuation — is expected to apply, but liraglutide-specific long-term discontinuation data is thinner than for its newer competitors.
Head-to-head performance against newer drugs favors semaglutide and tirzepatide in the trials that have compared them directly (see those profiles); liraglutide's own placebo-controlled record remains real, but by trial evidence it is no longer the most effective drug in its class.
Thyroid C-cell tumors, flagged in rodent studies, carry the same boxed warning and unresolved human-risk question as the rest of the GLP-1 class.
Use beyond several years is not directly answered by either pivotal trial — LEADER followed patients for a median 3.8 years, and SCALE's main phase ran 56 weeks.

Registry and study records

LEADER: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes: ClinicalTrials.gov NCT01179048 · registered enrollment 9,341 (published trial n=9,340), completed 2015, results posted; Marso et al., NEJM 2016
SCALE Obesity and Prediabetes: ClinicalTrials.gov NCT01272219 · n=3,731, completed 2015, results posted; Pi-Sunyer et al., NEJM 2015

See the full Evidence Index →

Evidence last reviewed: September 2026. Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.