Liraglutide

An acylated 31-amino-acid analog of human GLP-1 dosed once daily by subcutaneous injection, approved for type 2 diabetes in 2010 and for chronic weight management in 2014 as the first GLP-1 receptor agonist licensed for obesity.

Also referenced as: Victoza, Saxenda, NN2211, NN-2211

Also appears in: Metabolic

What is Liraglutide?

Liraglutide is a genuine peptide drug: a 31-residue analog of human GLP-1(7-37) sharing roughly 97% of the native sequence, differing by a single Lys34→Arg substitution and by a C16 palmitic acid attached to Lys26 through a glutamic acid spacer. The substitution exists only to make the acylation site unique — with Lys34 replaced, the fatty acid can attach at one position and nowhere else.

That fatty-acid chain is the whole design. It drives self-association into heptamers at the injection site and reversible binding to serum albumin in circulation, which together slow absorption, shield the molecule from dipeptidyl peptidase-4 cleavage, and stretch the plasma half-life to roughly 13 hours — long enough for once-daily subcutaneous dosing, where native GLP-1 lasts minutes.

It appears in research-peptide catalogs for two reasons that have little to do with each other. First, it is the compound that proved the acylation strategy later scaled up into semaglutide, and it accumulated one of the deepest trial records of any GLP-1 receptor agonist along the way. Second, both of its brands are now off-patent, and its fall from clinical fashion has left it circulating as bulk material alongside the incretin drugs that displaced it.

How it works

• GLP-1 receptor agonism with an engineered half-life. Liraglutide was selected from a series of fatty-acid-acylated GLP-1 derivatives explicitly designed for once-daily pharmacokinetics (Knudsen et al., Journal of Medicinal Chemistry, 2000;43(9):1664–1669). The albumin-binding acyl chain, not the peptide backbone, is what separates liraglutide from endogenous GLP-1; receptor pharmacology is otherwise close to native.
• Glucose-dependent insulin and glucagon effects. One week of liraglutide in adults with type 2 diabetes improved 24-hour glycemia, enhanced beta-cell function, suppressed alpha-cell glucagon output, and reduced endogenous glucose release (Degn et al., Diabetes, 2004;53(5):1187–1194). The insulinotropic effect is conditional on elevated glucose, which is why GLP-1 agonism alone carries a low intrinsic hypoglycemia risk.
• Appetite suppression via the hypothalamic arcuate nucleus. Peripherally injected fluorescent liraglutide reached circumventricular organs and bound neurons in the arcuate nucleus, where it was internalized by POMC/CART neurons; NPY/AgRP neurons were inhibited indirectly through GABA-dependent signaling. Weight loss was independent of GLP-1 receptors in the vagus nerve, area postrema, and paraventricular nucleus (Secher et al., Journal of Clinical Investigation, 2014;124(10):4473–4488).
• Gastric emptying is a smaller contributor than commonly assumed. In obese non-diabetic adults, five-hour gastric emptying was statistically equivalent to placebo at both 1.8 mg and 3.0 mg; only the first hour was measurably slowed, by 23% at 3.0 mg — the 13% seen at 1.8 mg did not reach significance. Satiety ratings rose and ad libitum energy intake fell about 16% at both doses (van Can et al., International Journal of Obesity, 2014;38(6):784–793). The satiety effect and the emptying effect do not track together.

Research status

Liraglutide has one of the deepest human evidence bases of any peptide, and it is unusual in that its problems are competitive rather than evidentiary.

Type 2 diabetes. The LEAD program established liraglutide in diabetes and led to Victoza’s approval on January 25, 2010 (NDA 022341) — the first once-daily GLP-1 analog in the United States. LEAD-6, the head-to-head against twice-daily exenatide in a 26-week open-label trial, cut HbA1c by 1.12 percentage points versus 0.79 with exenatide, with less persistent nausea and less minor hypoglycemia, though postprandial glucose control after breakfast and dinner was worse (Buse et al., Lancet, 2009;374(9683):39–47). Pediatric extension came later: among 134 treated children and adolescents with type 2 diabetes, liraglutide added to metformin lowered HbA1c by an estimated 1.06 percentage points versus placebo at 26 weeks, widening to 1.30 points by 52 weeks (Tamborlane et al., New England Journal of Medicine, 2019;381(7):637–646).

Obesity — the SCALE program. Saxenda was approved on December 23, 2014 (NDA 206321), making liraglutide 3.0 mg the first GLP-1 receptor agonist licensed for chronic weight management. The pivotal trial randomized 3,731 adults without diabetes for 56 weeks: mean weight loss was 8.4 kg with liraglutide versus 2.8 kg with placebo (difference −5.6 kg), with 63.2% versus 27.1% losing at least 5% and 33.1% versus 10.6% losing more than 10% (Pi-Sunyer et al., New England Journal of Medicine, 2015;373(1):11–22). Companion trials covered adjacent questions: weight maintenance after a low-calorie-diet run-in, where liraglutide produced a further 6.2% loss versus 0.2% on placebo over 56 weeks (Wadden et al., International Journal of Obesity, 2013;37(11):1443–1451); weight loss in type 2 diabetes (Davies et al., JAMA, 2015;314(7):687–699); and moderate-to-severe obstructive sleep apnea, where the apnea-hypopnea index fell 12.2 versus 6.1 events per hour at 32 weeks (Blackman et al., International Journal of Obesity, 2016;40(8):1310–1319). In adolescents aged 12 to under 18, the BMI standard-deviation score fell by an estimated 0.22 more than placebo at 56 weeks, with body weight 4.50 kg lower (Kelly et al., New England Journal of Medicine, 2020;382(22):2117–2128); FDA extended the weight-management indication to patients 12 and older on December 4, 2020.

Cardiovascular outcomes. LEADER randomized 9,340 adults with type 2 diabetes and high cardiovascular risk, followed for a median 3.8 years. The composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke occurred in 13.0% on liraglutide versus 14.9% on placebo (hazard ratio 0.87, 95% CI 0.78–0.97; P=0.01 for superiority), with cardiovascular death at 4.7% versus 6.0% (hazard ratio 0.78) and all-cause death at 8.2% versus 9.6% (Marso et al., New England Journal of Medicine, 2016;375(4):311–322). This is a genuine outcomes result, not a surrogate endpoint.

Where it loses. STEP 8 put liraglutide 3.0 mg directly against once-weekly semaglutide 2.4 mg in 338 adults over 68 weeks. Mean weight change was −15.8% with semaglutide versus −6.4% with liraglutide (difference −9.4 percentage points), and the gap widened at every response threshold: 20% or more weight loss was reached by 38.5% versus 6.0%. Discontinuation for any reason ran 13.5% versus 27.6% (Rubino et al., JAMA, 2022;327(2):138–150). Liraglutide is the reference arm that newer agents are measured against, and it is beaten.

Failures and unfinished programs. In type 1 diabetes, ADJUNCT ONE randomized 1,398 adults to liraglutide or placebo on top of treat-to-target insulin for 52 weeks; the HbA1c advantage was only 0.20 percentage points at the 1.8 mg dose, symptomatic hypoglycemia rose across the liraglutide arms — significantly at 1.2 mg and 1.8 mg — and hyperglycemia with ketosis more than doubled at 1.8 mg (rate ratio 2.22). The authors concluded these findings limited clinical use, and no type 1 indication was pursued (Mathieu et al., Diabetes Care, 2016;39(10):1702–1710). In Alzheimer’s disease, the ELAD Phase 2b trial (NCT01843075) randomized 204 participants with mild-to-moderate disease and no diabetes to 52 weeks of daily liraglutide; the primary endpoint, change in cerebral glucose metabolic rate, was not met (difference −0.17, 95% CI −0.39 to 0.06, P=0.14). The secondary picture is thinner than it is usually reported: the executive-function domain of the Alzheimer’s Disease Assessment Scale favored liraglutide (0.15, 95% CI 0.03–0.28) on an unadjusted P of 0.01, while ADCS-ADL (P=0.65) and CDR-Sum of Boxes (P=0.81) showed no difference (Edison et al., Nature Medicine, 2026;32(1):353–361). Press coverage describing an 18% slowing of cognitive decline draws on that single unadjusted secondary domain, not on the endpoint the trial was designed to test. In non-alcoholic steatohepatitis, the small LEAN Phase 2 trial reported histological resolution in 9 of 23 liraglutide patients versus 2 of 22 on placebo (Armstrong et al., Lancet, 2016;387(10019):679–690) — a positive signal in 52 patients that was never advanced to Phase 3 for liraglutide.

Common dosage forms

• Multi-dose prefilled injection pens at 6 mg/mL (18 mg per 3 mL cartridge), the presentation used in every approved single-ingredient product and in essentially every clinical trial. Diabetes-labeled pens dial to a lower maximum than weight-management pens; the concentration is identical.
• Generic prefilled pens. FDA approved the first generic of Victoza in December 2024 and the first generic of Saxenda in August 2025 — the latter being the first generic GLP-1 receptor agonist approved for weight management in the United States. Both match the reference pen presentation at 18 mg per 3 mL.
• Fixed-ratio combination pens pairing liraglutide with insulin degludec (Xultophy 100/3.6, 10.8 mg liraglutide per 3 mL — a lower liraglutide concentration of 3.6 mg/mL), a distinct product rather than liraglutide alone.
• Lyophilized powder in vials, typically labeled in milligrams for reconstitution, in research-market listings. This format has no counterpart in the approved product line or in the pivotal trials, which used prefilled solution pens.
• Multi-compound blend vials combining liraglutide with other metabolic peptides, where the per-vial liraglutide content is frequently not stated separately.

This section describes formats only and is not dosing guidance.

Key considerations

• Approved, off-patent, and being retired by its originator. Liraglutide holds full FDA approval across type 2 diabetes (2010, extended to ages 10+), chronic weight management (2014, extended to ages 12+ in 2020), and cardiovascular risk reduction in type 2 diabetes. Generics now exist for both brands. Separately, Novo Nordisk has posted advance notice that it is discontinuing the Saxenda brand, with last shipments to wholesalers planned for late January 2027, describing this as a portfolio decision unrelated to safety or quality. Approved-product availability and brand availability are diverging.
• The compounding pathway is narrowing. On April 30, 2026, FDA proposed to exclude semaglutide, tirzepatide, and liraglutide from the 503B bulks list, finding no clinical need for outsourcing facilities to compound them from bulk substances. This is a proposal rather than a final determination — the notice published in the Federal Register on May 1, 2026 (Docket No. FDA-2018-N-3240) took comments through June 30, 2026 — and it governs 503B outsourcing facilities specifically, leaving 503A pharmacy compounding and shortage-period compounding on separate footing. Bulk liraglutide sold as research material has never been an approved drug product, and material labeled for research use carries no identity, purity, or sterility assurance from that approval.
• Boxed warning and known safety signals. Approved labeling carries a boxed warning for thyroid C-cell tumors — dose- and duration-dependent adenomas and carcinomas in both rats and mice at clinically relevant exposures, with human relevance undetermined — and contraindicates use with a personal or family history of medullary thyroid carcinoma or MEN 2. Warnings and precautions across the two labels cover acute pancreatitis, acute gallbladder disease, hypoglycemia when combined with insulin or an insulin secretagogue, acute kidney injury due to volume depletion, severe gastrointestinal reactions, hypersensitivity, and pulmonary aspiration during general anesthesia or deep sedation; the weight-management label adds heart rate increase. One warning has come off rather than on: in January 2026 FDA asked manufacturers to remove the suicidal behavior and ideation warning from GLP-1 labels after a 91-trial meta-analysis of roughly 108,000 participants found no increased risk — so older summaries of this drug list a warning the current label does not. Tolerability is a practical limit as well as a labeled one: 27.6% of the liraglutide arm discontinued treatment for any reason in STEP 8, roughly double the semaglutide arm.
• It is the weakest and most demanding of the incretin drugs it gets compared with. Daily injection rather than weekly, and roughly 6% versus 16% mean weight loss against semaglutide 2.4 mg in the one trial that tested them head to head. No randomized trial has compared liraglutide directly with tirzepatide, so cross-trial rankings against the dual GIP/GLP-1 agonist rest on separate placebo-controlled studies rather than on a direct comparison.
• Naming and product confusions are frequent. Victoza and Saxenda are the same molecule at different labeled maximum doses for different indications, and the labels are not interchangeable. NN2211 is the development code for the molecule while NN8022 designates the obesity trial program, so the two appear in different literatures. SCALE and LEAD are trial-program names, not formulations. Liraglutide, lixisenatide, and semaglutide are three distinct compounds whose names are easy to transpose, and Xultophy is a combination product rather than liraglutide by itself.