Peringatan Keamanan

Overdoses of up to 4 mg in one ingestion have been reported, with nausea being the most commonly reported symptom. All patients in clinical trials who experienced an overdose recovered fully.L8693 Appropriate supportive care should be given according and dictated by the patient's condition. Prolonged observation and treatment may be required, as the half-life of this drug is about one week.L8681 There is no antidote to an overdose with semaglutide.L8693

Semaglutide

DB13928

small molecule approved investigational

Deskripsi

Semaglutide is a glucagon-like peptide 1 (GLP-1) analog used to manage type 2 diabetes along with lifestyle changes, such as dietary restrictions and increased physical activity.A31421,L8681 Other members of this drug class include Exenatide and Liraglutide. Semaglutide was developed by Novo Nordisk and approved by the FDA for subcutaneous injection in December 2017.L8681 The tablet formulation was approved for oral administration in September 2019. Semaglutide works by binding to and activating the GLP-1 receptor, thereby stimulating insulin secretion and reducing blood glucose.L8678

The subcutaneous injection is administered once weekly and the tablet is administered once a day. Semaglutide offers a competitive advantage over other drugs used to manage diabetes, which may require several daily doses. Clinical trials have determined that this drug reduces glycosylated hemoglobin (HbA1c) levels and reduces body weight, proving to be effective for patients with type 2 diabetes.A186053 In June 2021, semaglutide was approved by the FDA for chronic weight management in adults with general obesity or overweight who have at least one weight-related condition, marking semaglutide as the first approved drug for such use since 2014.L34485 The use of semaglutide in weight management is also approved by Health Canada L39347 and the EMA.L41335

On May 31, 2023, the FDA issued a warning regarding the use of compounded semaglutide after receiving adverse event reports. The use of salt forms of semaglutide, including semaglutide sodium and semaglutide acetate, has not been proven to be safe or effective.L46726

Struktur Molekul 2D

Berat 4113.641
Wujud liquid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) One of the major properties of semaglutide is its long half-life of 168 h.[A31425] The long half-life is attributed to its albumin binding. This lowers the renal clearance and protects semaglutide from metabolic breakdown.[L8678,L8681]
Volume Distribusi The volume of distribution of semaglutide is 8L to 9.4L. It crosses the placenta in rats.[A31425,L8681]
Klirens (Clearance) The clearance rate of semaglutide is 0.039 L/h according to one clinical study.[A31425] On the FDA label, semaglutide clearance is reported to be about 0.05 L/h in patients with type 2 diabetes mellitus.[L8681]

Absorpsi

The Cmax of semaglutide was 10.9 nmol/L, with AUC of 3123.4 nmol h/L and a Tmax of 56 h in one clinical trial, achieved within 1-3 days.A31425,L8681 The absolute bioavailability is 89%.L8681 Steady-state concentration of the oral tablet is achieved in 4-5 weeks.A186089 Average steady state concentrations of semaglutide are the mean steady state concentrations after dosing at 0.5mg to 1mg range from 16 nmol/L to 30 nmol/L.L8693

Metabolisme

Semaglutide is cleaved at the peptide backbone, followed by ??oxidation of the fatty acid chain.A186092 Naturally occurring GLP?1 is quickly metabolized by dipeptidyl peptidase?4 (DPP?4) and other enzymes, which is ubiquitous in human tissues. Chemical structure modifications render semaglutide less susceptible to enzymatic degradation by gastrointestinal DPP?4 enzymes.A186092 It is slowly and extensively metabolized, with about 83% of the administered dose measured in the plasma as unchanged drug. Neural endopeptidase (NEP) is another enzyme that metabolizes this drug. DPP-4 inactivates semaglutide, truncating the N-terminal segment while NEP hydrolyzes peptide bondsSix different metabolites of semaglutide have been identified in human plasma. The major metabolite, named P3, accounts for about 7.7% of an ingested dose.A31425

Rute Eliminasi

This drug is mainly cleared by the kidneys, and is found excreted in both the urine and feces.A186092 The main elimination route is the urine by corresponding to 53% of an ingested radiolabeled dose, with 18.6% found in the feces. A smaller amount of 3.2% was found to be exhaled.A31425 Hepatic impairment does not appear to affect the clearance of this drug and dose adjustments are not required in patients with decreased liver function.A186092

Interaksi Makanan

2 Data
  • 1. Take on an empty stomach. For oral use of semaglutide, take 30 minutes before the first meal of the day.
  • 2. Take with plain water. For oral use of semaglutide, do not exceed 4 ounces of water (1/2 cup).

Interaksi Obat

603 Data
Pegvisomant The risk or severity of hypoglycemia can be increased when Pegvisomant is combined with Semaglutide.
Lipoic acid The risk or severity of hypoglycemia can be increased when Lipoic acid is combined with Semaglutide.
Moxifloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Moxifloxacin.
Grepafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Grepafloxacin.
Enoxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Enoxacin.
Pefloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Pefloxacin.
Ciprofloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Ciprofloxacin.
Trovafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Trovafloxacin.
Nalidixic acid The therapeutic efficacy of Semaglutide can be increased when used in combination with Nalidixic acid.
Rosoxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Rosoxacin.
Cinoxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Cinoxacin.
Lomefloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Lomefloxacin.
Gatifloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Gatifloxacin.
Norfloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Norfloxacin.
Levofloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Levofloxacin.
Gemifloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Gemifloxacin.
Ofloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Ofloxacin.
Sparfloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Sparfloxacin.
Temafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Temafloxacin.
Fleroxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Fleroxacin.
Technetium Tc-99m ciprofloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Technetium Tc-99m ciprofloxacin.
Garenoxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Garenoxacin.
Nemonoxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Nemonoxacin.
Flumequine The therapeutic efficacy of Semaglutide can be increased when used in combination with Flumequine.
Enrofloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Enrofloxacin.
Orbifloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Orbifloxacin.
Sarafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Sarafloxacin.
Difloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Difloxacin.
Pazufloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Pazufloxacin.
Prulifloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Prulifloxacin.
Delafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Delafloxacin.
Sitafloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Sitafloxacin.
Oxolinic acid The therapeutic efficacy of Semaglutide can be increased when used in combination with Oxolinic acid.
Rufloxacin The therapeutic efficacy of Semaglutide can be increased when used in combination with Rufloxacin.
Pipemidic acid The therapeutic efficacy of Semaglutide can be increased when used in combination with Pipemidic acid.
Methyclothiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Methyclothiazide.
Chlorthalidone The therapeutic efficacy of Semaglutide can be decreased when used in combination with Chlorthalidone.
Bendroflumethiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Bendroflumethiazide.
Metolazone The therapeutic efficacy of Semaglutide can be decreased when used in combination with Metolazone.
Benzthiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Benzthiazide.
Hydroflumethiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Hydroflumethiazide.
Indapamide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Indapamide.
Chlorothiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Chlorothiazide.
Hydrochlorothiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Hydrochlorothiazide.
Trichlormethiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Trichlormethiazide.
Polythiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Polythiazide.
Quinethazone The therapeutic efficacy of Semaglutide can be decreased when used in combination with Quinethazone.
Cyclopenthiazide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Cyclopenthiazide.
Epitizide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Epitizide.
Amitriptyline Amitriptyline may decrease the hypoglycemic activities of Semaglutide.
Protriptyline Protriptyline may decrease the hypoglycemic activities of Semaglutide.
Imipramine Imipramine may decrease the hypoglycemic activities of Semaglutide.
Nortriptyline Nortriptyline may decrease the hypoglycemic activities of Semaglutide.
Amoxapine Amoxapine may decrease the hypoglycemic activities of Semaglutide.
Trimipramine Trimipramine may decrease the hypoglycemic activities of Semaglutide.
Doxepin Doxepin may decrease the hypoglycemic activities of Semaglutide.
Desipramine Desipramine may decrease the hypoglycemic activities of Semaglutide.
Clomipramine Clomipramine may decrease the hypoglycemic activities of Semaglutide.
Amineptine Amineptine may decrease the hypoglycemic activities of Semaglutide.
Dimetacrine Dimetacrine may decrease the hypoglycemic activities of Semaglutide.
Butriptyline Butriptyline may decrease the hypoglycemic activities of Semaglutide.
Dosulepin Dosulepin may decrease the hypoglycemic activities of Semaglutide.
Tianeptine Tianeptine may decrease the hypoglycemic activities of Semaglutide.
Oxaprotiline Oxaprotiline may decrease the hypoglycemic activities of Semaglutide.
Opipramol Opipramol may decrease the hypoglycemic activities of Semaglutide.
Amitriptylinoxide Amitriptylinoxide may decrease the hypoglycemic activities of Semaglutide.
Dibenzepin Dibenzepin may decrease the hypoglycemic activities of Semaglutide.
Quinupramine Quinupramine may decrease the hypoglycemic activities of Semaglutide.
Melitracen Melitracen may decrease the hypoglycemic activities of Semaglutide.
Lofepramine Lofepramine may decrease the hypoglycemic activities of Semaglutide.
Iprindole Iprindole may decrease the hypoglycemic activities of Semaglutide.
Imipramine oxide Imipramine oxide may decrease the hypoglycemic activities of Semaglutide.
Glimepiride Semaglutide may increase the hypoglycemic activities of Glimepiride.
Acetohexamide Semaglutide may increase the hypoglycemic activities of Acetohexamide.
Chlorpropamide Semaglutide may increase the hypoglycemic activities of Chlorpropamide.
Tolazamide Semaglutide may increase the hypoglycemic activities of Tolazamide.
Glyburide Semaglutide may increase the hypoglycemic activities of Glyburide.
Glipizide Semaglutide may increase the hypoglycemic activities of Glipizide.
Gliclazide Semaglutide may increase the hypoglycemic activities of Gliclazide.
Tolbutamide Semaglutide may increase the hypoglycemic activities of Tolbutamide.
Gliquidone Semaglutide may increase the hypoglycemic activities of Gliquidone.
Glisoxepide Semaglutide may increase the hypoglycemic activities of Glisoxepide.
Glibornuride Semaglutide may increase the hypoglycemic activities of Glibornuride.
Carbutamide Semaglutide may increase the hypoglycemic activities of Carbutamide.
Metahexamide Semaglutide may increase the hypoglycemic activities of Metahexamide.
Dapagliflozin Dapagliflozin may increase the hypoglycemic activities of Semaglutide.
Canagliflozin Canagliflozin may increase the hypoglycemic activities of Semaglutide.
Leuprolide The therapeutic efficacy of Semaglutide can be decreased when used in combination with Leuprolide.
Goserelin The therapeutic efficacy of Semaglutide can be decreased when used in combination with Goserelin.
Nelfinavir The therapeutic efficacy of Semaglutide can be decreased when used in combination with Nelfinavir.
Indinavir The therapeutic efficacy of Semaglutide can be decreased when used in combination with Indinavir.
Ziprasidone The therapeutic efficacy of Semaglutide can be decreased when used in combination with Ziprasidone.
Etonogestrel The therapeutic efficacy of Semaglutide can be decreased when used in combination with Etonogestrel.
Desogestrel The therapeutic efficacy of Semaglutide can be decreased when used in combination with Desogestrel.
Olanzapine The therapeutic efficacy of Semaglutide can be decreased when used in combination with Olanzapine.
Megestrol acetate The therapeutic efficacy of Semaglutide can be decreased when used in combination with Megestrol acetate.
Clozapine The therapeutic efficacy of Semaglutide can be decreased when used in combination with Clozapine.
Levonorgestrel The therapeutic efficacy of Semaglutide can be decreased when used in combination with Levonorgestrel.
Progesterone The therapeutic efficacy of Semaglutide can be decreased when used in combination with Progesterone.
Chlorpromazine The therapeutic efficacy of Semaglutide can be decreased when used in combination with Chlorpromazine.

Target Protein

Glucagon-like peptide 1 receptor GLP1R

Referensi & Sumber

Synthesis reference: Synthesis of SemaglutideJ. CJPH, 2018, 49(06): 742-.
Artikel (PubMed)
  • PMID: 24608440
    Gotfredsen CF, Molck AM, Thorup I, Nyborg NC, Salanti Z, Knudsen LB, Larsen MO: The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates. Diabetes. 2014 Jul;63(7):2486-97. doi: 10.2337/db13-1087. Epub 2014 Mar 7.
  • PMID: 28266779
    Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, Hjerpsted JB: Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017 Sep;19(9):1242-1251. doi: 10.1111/dom.12932. Epub 2017 May 5.
  • PMID: 24140094
    Lee YS, Jun HS: Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism. 2014 Jan;63(1):9-19. doi: 10.1016/j.metabol.2013.09.010. Epub 2013 Oct 17.
  • PMID: 28323117
    Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjornsdottir I, Pedersen PJ, Rowe E, Derving Karsbol J, Pedersen ML: Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41. doi: 10.1016/j.ejps.2017.03.020. Epub 2017 Mar 16.
  • PMID: 29766634
    Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA: Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
  • PMID: 29756388
    Andreadis P, Karagiannis T, Malandris K, Avgerinos I, Liakos A, Manolopoulos A, Bekiari E, Matthews DR, Tsapas A: Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Obes Metab. 2018 Sep;20(9):2255-2263. doi: 10.1111/dom.13361. Epub 2018 Jun 10.
  • PMID: 30623143
    Rakipovski G, Rolin B, Nohr J, Klewe I, Frederiksen KS, Augustin R, Hecksher-Sorensen J, Ingvorsen C, Polex-Wolf J, Knudsen LB: The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE(-/-) and LDLr(-/-) Mice by a Mechanism That Includes Inflammatory Pathways. JACC Basic Transl Sci. 2018 Nov 21;3(6):844-857. doi: 10.1016/j.jacbts.2018.09.004. eCollection 2018 Dec.
  • PMID: 30929417
    Kim KK: Understanding the Mechanism of Action and Clinical Implications of Anti-Obesity Drugs Recently Approved in Korea. Korean J Fam Med. 2019 Mar;40(2):63-71. doi: 10.4082/kjfm.19.0013. Epub 2019 Mar 20.
Menampilkan 8 dari 11 artikel.

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