liraglutide (Victoza, Saxenda)
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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]
Dosage
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
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of SGLT-2 inhititor (flozin) in combination with GLP1-agonist
- drug interaction(s) of acetaminophen in combination with GLP1-agonist
- drug interaction(s) of fluoroquinolones with hypoglycemic agents
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]
- low calorie diet, exercise & liraglutide bests any one or two of combination of three in maintenance & enhancement of weight reduction[23]
Notes
More general terms
Component of
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18819705
- ↑ 2.0 2.1 2.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23141817 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61267-7/fulltext - ↑ 3.0 3.1 3.2 FDA NEWS RELEASE, Jan. 25, 2010 FDA Approves New Treatment for Type 2 Diabetes http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198638.htm
- ↑ 4.0 4.1 Prescriber's Letter 17(3): 2010 New Drug: Victoza (Liraglutide) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260304&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/20417856 doi:10.1016/S0140-6736(10)60307-8
- ↑ 6.0 6.1 6.2 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
- ↑ 7.0 7.1 7.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22236411 <Internet> http://www.bmj.com/node/557082
Padwal R Glucagon-like peptide-1 agonists BMJ 2012;344:d7282 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22236410 <Internet> 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 - ↑ 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
- ↑ 9.0 9.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26132939 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26132945 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1506236 - ↑ 10.0 10.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26284720 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2428956
- ↑ 11.0 11.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26512041 <Internet> http://www.bmj.com/content/351/bmj.h5364
- ↑ 12.0 12.1 Marso SP, Daniels GH, Brown-Frandsen K et al Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. June 13, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27295427 <Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/26605932 - ↑ 13.0 13.1 13.2 Varanasi A, Bellini N, Rawal D, Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011 Jul;165(1):77-84. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21646283 Free Article
- ↑ 14.0 14.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28237263 <Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/28237265 - ↑ 15.0 15.1 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
- ↑ 16.0 16.1 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 - ↑ 17.0 17.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28854085 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28854097 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1708949 - ↑ 18.0 18.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30508430 <Internet> http://annals.org/aim/article-abstract/2717732/effect-liraglutide-cardiovascular-outcomes-elderly-patients-post-hoc-analysis-randomized
- ↑ 19.0 19.1 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
- ↑ 20.0 20.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31399438 https://care.diabetesjournals.org/content/42/10/1912
- ↑ 21.0 21.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31721979 Free PMC Article https://jamanetwork.com/journals/jamacardiology/fullarticle/2754760
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/19853906
- ↑ 23.0 23.1 23.2 Lundgren JR et al. Healthy weight loss maintenance with exercise, liraglutide, or both combined. N Engl J Med 2021 May 6; 384:1719 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33951361 https://www.nejm.org/doi/10.1056/NEJMoa2028198
- ↑ 24.0 24.1 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
- ↑ 25.0 25.1 NEJM Knowledge+ Endocrinology
- ↑ 26.0 26.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37494014 PMCID: PMC10372755 Free PMC article. https://jamanetwork.com/journals/jamasurgery/fullarticle/2807724
- ↑ 27.0 27.1 Medscape: liraglutide Rx https://reference.medscape.com/drug/victoza-saxenda-liraglutide-999449