Liraglutide: Difference between revisions

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| generic = Liraglutide

| brand = Victoza (T2DM), Saxenda (obesity)

| structure = 31-amino-acid acylated peptide analog of human [[GLP-1]] (7–37), with Arg34 substitution and a C16 palmitic acid linked via γGlu spacer at Lys26 — drives albumin binding for a ~13-hour half-life supporting once-daily dosing.<ref name="knudsen2000">Knudsen LB, Nielsen PF, Huusfeldt PO et al. (2000). Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. ''J Med Chem'' 43(9):1664–9. doi:10.1021/jm9909645</ref>

| structure =

| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · [[Anti-obesity medicines|Anti-obesity]] · [[Cardiovascular risk reduction]] agent

| mechanism = ~~Selective~~ agonist of the [[GLP-1 receptor]]. Produces glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression, and cardiovascular benefits independent of glycemia.<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351.</ref>

| mechanism = Once-daily agonist of the [[GLP-1 receptor]].

| uses = [[Type 2 diabetes mellitus]] (incl. pediatric ≥10 y) · [[Obesity]] (incl. pediatric ≥12 y) · [[Cardiovascular risk reduction]] in T2DM

| starting_dose = Victoza: 0.6 mg SC daily × 1 wk<ref name="victoza-label">US FDA. ''Victoza (liraglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022341s027lbl.pdf</ref> · Saxenda: 0.6 mg SC daily × 1 wk<ref name="saxenda-label">US FDA. ''Saxenda (liraglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206321Orig1s000lbl.pdf</ref>

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Clinically, liraglutide is the first GLP-1 RA shown to reduce cardiovascular events in T2DM ([[LEADER trial|LEADER]]) and remains the only GLP-1 RA with formal pediatric approval — Victoza for T2DM in children ≥10 y, Saxenda for obesity in adolescents ≥12 y.<ref name="leader2016">Marso SP et al. (2016). Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). ''NEJM'' 375:311–22. doi:10.1056/NEJMoa1603827</ref><ref name="victoza-label"/><ref name="saxenda-label"/>

| pharmacokinetics = The C16 fatty acid drives non-covalent albumin binding (~98%), protecting from DPP-4 cleavage and slowing renal clearance — terminal half-life ~13 hours, supporting once-daily dosing.<ref name="knudsen2000"/><ref name="victoza-label"/> Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.<ref name="victoza-label"/>

| pharmacokinetics = '''Chemistry'''. 31-amino-acid acylated peptide analog of human [[GLP-1]] (7–37), with Arg34 substitution and a C16 palmitic acid linked via γGlu spacer at Lys26 — drives albumin binding for a ~13-hour half-life supporting once-daily dosing.<ref name="knudsen2000">Knudsen LB, Nielsen PF, Huusfeldt PO et al. (2000). Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. ''J Med Chem'' 43(9):1664–9. doi:10.1021/jm9909645</ref>

The C16 fatty acid drives non-covalent albumin binding (~98%), protecting from DPP-4 cleavage and slowing renal clearance — terminal half-life ~13 hours, supporting once-daily dosing.<ref name="knudsen2000"/><ref name="victoza-label"/> Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.<ref name="victoza-label"/>

| pharmacodynamics = '''Receptor pharmacology'''. Selective agonist of the [[GLP-1 receptor]]. Produces glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression, and cardiovascular benefits independent of glycemia.<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351.</ref>

~~| pharmacodynamics =~~ At maintenance doses:

At maintenance doses:

* HbA1c reduction of ~1.0–1.5 percentage points at 1.8 mg/day (T2DM)<ref name="victoza-label"/>

* Weight loss of ~2–3 kg at 1.8 mg/day in T2DM; ~5–8 kg (~5–10% body weight) at 3.0 mg/day in obesity without T2DM (SCALE trials)<ref name="scale">Pi-Sunyer X, Astrup A, Fujioka K et al. (2015). A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes). ''NEJM'' 373(1):11–22. doi:10.1056/NEJMoa1411892</ref>

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