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liraglutide (Victoza, Saxenda)

Indications: - type 2 diabetes* (Victoza) - addition of liraglutide to insulin in patients with long-standing type 2 diabetes improves glycemic control [11] - reduces risk of type 2 diabetes in patients with prediabetes [13] - reduces risk of albuminuria in type 2 diabetes (6 vs 7% for placebo) [17] - approved for use in patients >= 10 years of age [19] - type 1 diabetes - adjunct to insulin, may improve glycemic control [13] - obesity (Sandexa) [7] (BMI >= 30) - may add an additional 8% weight loss after bariatric surgery [26] - *BMI >= 27 + hypertension, type 2 diabetes or dyslipidemia - helps nondiabetic patients lose weight [9] - reduces 4 year cardiovascular mortality (4.7 vs 6.0%) & all-cause mortality (8.2 vs 9.6%) in high-risk patients with type 2 diabetes [12,15] - FDA-approval for cardiovascular risk reduction in patients with type 2 diabetes (Aug 2017) [16] - may reduce cardiovascular events in adults aged >= 75 years [18] & those at high risk of cardiovascular events [21] * not first line Contraindications: - pancreatitis - history of pancreatitis is relative contraindication - family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia-2 (MEN2) - gastroparesis [25] - does not reduce hospitalization due to heart failure [24] Pregnancy category: C Dosage: - 0.6-1.8 mg SQ QD pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg (6 mg/mL, 3 mL) Dosage adjustment in renal failure: - use with caution in patients with severe renal impairment [27] Adverse effects: - hypoglycemia less than glimepiride - GI side effects most common (41% overall) - nausea (28.4%), diarrhea (17.1%), vomiting (10.9%), constipation (9.9%) - headache - allergic-like reactions: hives - pancreatitis (rare) [3,4,6] - serious gall bladder events [14]; gallstone disease [20] - not associated with an increased risk for cardiovascular events in patients at low risk - dose-dependent & treatment-duration-dependent thyroid C-cell tumors (including medullary thyroid carcinoma) at clinically relevant exposures [3,6] Drug interactions: - theoretically slows gastric emptying - does not affect absorption of any tested orally administered pharmaceuticals to any clinically relevant extent Mechanism of action: - glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic) - appetite suppressant, weight reduction [7,10] Clinical trials: - outperforms sitagliptin in metformin resistant diabetes [5] - mean decline in HbA1c level: 1.48% with liraglutide & 1.28% with exenatide [2] - 60% of liraglutide recipients vs 53% of exenatide recipients achieved HbA1c levels <7.0% - mean weight loss was about 3 kg in both groups - GI side effects were somewhat more common with liraglutide [2] - low calorie diet, exercise & liraglutide bests any one or two of combination of three in maintenance & enhancement of weight reduction [23] - GI side effects were more common with liraglutide [23] Notes: - manufactured by Novo Nordisk of Bagsvaerd, Denmark

Interactions

drug adverse effects of hypoglycemic agents

General

glucagon-like peptide 1 (GLP-1) receptor agonist; incretin mimetic; GLP-1 mimetic; GLP-1 agonist; glutide; GLP-1RA

Database Correlations

PUBCHEM cid=16134956

References

  1. Garber A et al Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): A randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009 Feb 7; 373:473. PMID: 18819705
  2. Buse JB et al Liraglutide once a day versus exenatide twice a day for type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009 Jul 4; 374:39. PMID: 19515413 - Buse JB et al Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet 2012 Nov 7 PMID: 23141817 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61267-7/fulltext
  3. FDA NEWS RELEASE, Jan. 25, 2010 FDA Approves New Treatment for Type 2 Diabetes http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198638.htm
  4. Prescriber's Letter 17(3): 2010 New Drug: Victoza (Liraglutide) Detail-Document#: 260304 (subscription needed) http://www.prescribersletter.com
  5. Pratley RE et al Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial The Lancet 2010, 375(9724):1447-1456 PMID: 20417856 doi:10.1016/S0140-6736(10)60307-8
  6. FDA MedWatch: 06/13/2011 Victoza (liraglutide [rDNA origin]) Injection: REMS - Risk of Thyroid C-cell Tumors, Acute Pancreatitis http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258826.htm
  7. Vilsbol T Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials BMJ 2012;344:d7771 PMID: 22236411 http://www.bmj.com/node/557082 - Padwal R Glucagon-like peptide-1 agonists BMJ 2012;344:d7282 PMID: 22236410 http://www.bmj.com//node/557081 - Medscape Oncology. FDA Approvals > Medscape Medical News December 23, 2014 FDA Approves Liraglutide (Saxenda) for Weight Loss. http://www.medscape.com/viewarticle/837147 - FDA News Release. December 23, 2014 FDA approves weight-management drug Saxenda http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm
  8. FDA Briefing Document. NDA 206321 Liraglutide Injection. 3 mg Endocrinologic and Drugs Advistory Committtee Meeting Sept 11, 2014 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf
  9. Pi-Sunyer X, Astrup S, Fujioka K et al A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373:11-22. July 2, 2015 PMID: 26132939 http://www.nejm.org/doi/full/10.1056/NEJMoa1411892 - Siraj ES, Williams KJ Another Agent for Obesity - Will This Time Be Different? N Engl J Med 2015; 373:82-83. July 2, 2015 PMID: 26132945 http://www.nejm.org/doi/full/10.1056/NEJMe1506236
  10. Davies MJ et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA 2015 Aug 18; 314:687 PMID: 26284720 http://jama.jamanetwork.com/article.aspx?articleid=2428956
  11. Lind M et al Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (MDI Liraglutide trial). BMJ 2015;351:h5364 PMID: 26512041 http://www.bmj.com/content/351/bmj.h5364
  12. Marso SP, Daniels GH, Brown-Frandsen K et al Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. June 13, 2016 PMID: 27295427 http://www.nejm.org/doi/full/10.1056/NEJMoa1603827 - Ingelfinger JR, Rosen CJ. Cardiac and renovascular complications in type 2 diabetes - Is there hope? N Engl J Med 2016 Jun 14 PMID: 26605932
  13. Varanasi A, Bellini N, Rawal D, Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011 Jul;165(1):77-84. PMID: 21646283 Free Article
  14. le Roux CW, Astrup A, Fujioka K et al 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. Feb 22, 2017 PMID: 28237263 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30069-7/fulltext - Farr OM, Mantzoros CS. Treating prediabetes in the obese: Are GLP-1 analogues the answer? Lancet 2017 Feb 22 PMID: 28237265
  15. Phend C Clear Sailing Likely for Victoza CV Indication - No major issues put forth for Tuesday FDA advisory committee. MedPage Today. June 19, 2017 https://www.medpagetoday.com/Cardiology/Prevention/66131
  16. Fiore K Another Diabetes Drug Scores Heart Indication. Liraglutide follows empagliflozin into cardiovascular approval. MedPage Today. August 25, 2017 https://www.medpagetoday.com/Endocrinology/Diabetes/67504 - Tucker ME FDA Grants Liraglutide Cardiovascular Events Indication Medscape - Aug 25, 2017. http://www.medscape.com/viewarticle/884726
  17. Mann JFE, Orsted DD, Brown-Frandsen K et al Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:839-848. August 31, 2017 PMID: 28854085 http://www.nejm.org/doi/full/10.1056/NEJMoa1616011 - de Boer IH A New Chapter for Diabetic Kidney Disease. N Engl J Med 2017; 377:885-887. August 31, 2017 PMID: 28854097 http://www.nejm.org/doi/full/10.1056/NEJMe1708949
  18. Gilbert MP, Bain SC, Franek E et al Effect of Liraglutide on Cardiovascular Outcomes in Elderly Patients: A Post Hoc Analysis of a Randomized Controlled Trial. Ann Intern Med. 2018. Dec 4. PMID: 30508430 http://annals.org/aim/article-abstract/2717732/effect-liraglutide-cardiovascular-outcomes-elderly-patients-post-hoc-analysis-randomized
  19. FDA News Release. June 17, 2019 FDA approves new treatment for pediatric patients with type 2 diabetes. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pediatric-patients-type-2-diabetes
  20. Nauck MA, Muus Ghorbani ML, Kreiner E et al. Effects of liraglutide compared with placebo on events of acute gallbladder or biliary disease in patients with type 2 diabetes at high risk for cardiovascular events in the LEADER randomized trial. Diabetes Care 2019 Oct; 42:1912 PMID: 31399438 https://care.diabetesjournals.org/content/42/10/1912
  21. Verma S, Bain SC, Buse JB et al Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events. A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019;4(12):1214-1220. Nov 13. PMID: 31721979 Free PMC Article https://jamanetwork.com/journals/jamacardiology/fullarticle/2754760
  22. Astrup A, Rossner S, Van Gaal L et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009 Nov 7; 374:1606. PMID: 19853906
  23. Lundgren JR et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med 2021 May 6; 384:1719 PMID: 33951361 https://www.nejm.org/doi/10.1056/NEJMoa2028198
  24. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  25. NEJM Knowledge+ Endocrinology
  26. Mok J et al. Safety and efficacy of liraglutide, 3.0 mg, once daily vs placebo in patients with poor weight loss following metabolic surgery: The BARI-OPTIMISE randomized clinical trial. JAMA Surg 2023 Jul 26; [e-pub]. PMID: 37494014 PMCID: PMC10372755 Free PMC article. https://jamanetwork.com/journals/jamasurgery/fullarticle/2807724
  27. Medscape: liraglutide Rx https://reference.medscape.com/drug/victoza-saxenda-liraglutide-999449

Component-of

degludec/liraglutide (Xultophy)