Suomen uutisissa mainitaan semaglutide- lääkkeen puute diabeetikoilla, koska lääkettä on alettu käyttää toiseen indikaatioon, obesitas, enenevästi. Kyse on lääkkeen injisoitavasta muodosta. Lääkkeestä on myös tablettimuoto diabeteksen hoitoon. Ruotsissa on 2 valmistetta semaglutidia:
Toinen on suun kautta otettava tablettimuoto.Rybelsus. Toinen on injektiomuoto Ozempic (NovoNordisk), josta Suomen lehdistä mainitsee.
Uutiset https://www.aamulehti.fi/uutiset/art-2000009091964.html
Elintärkeä diabeteslääke loppui Suomen apteekeista, syynä sen suuri suosio laihdutuslääkkeenä – ”Kaikki varastot on myyty loppuun” Ozempicia käytetään tyypin 2 diabeteksessa verensokerin hoitoon. Lääkkeellä on havaittu myös selvästi laihduttava vaikutus, mikä on saanut sen kysynnän rajuun kasvuun syksyn aikana….
Inkretiinilääkkeiden historiasta muutama artikkeli:
Vuodelta 2022 ( semaglutide)
Wegovy (semaglutide): a new weight loss drug for chronic weight management.
Singh G, Krauthamer M, Bjalme-Evans M. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID: 34706925 Free PMC article. Review.
Vuodelta 2021 (semaglutide)
Front Endocrinol (Lausanne) 2021 Jul 7;12:645563.
eCollection 2021. Safety of Semaglutide Mark M Smits 1 et al. DOI: 10.3389/fendo.2021.645563 Free PMC article
Vuodelta 2021 (lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, dulaglutide) https://www.eurekaselect.com/images/graphical-abstract/chyr/17/2/007.jpg
GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients
Author(s): Aschner Pablo et al. Volume 17, Issue 2, 2021 Published on: 24 November, 2020 DOI: 10.2174/1573402116999201124123549 Background: Diabetes is a chronic disease with high complexity that demands strategic medical care with a multifactorial risk-reduction approach. Over the past decade, the treatment of type 2 diabetes mellitus (T2DM) has entirely changed. One of the paradigm changes has been the arrival of new drugs that reduce cardiovascular risk beyond the reduction of A1C. Objective: Sodium-glucose cotransporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are two groups of antidiabetics drugs, which have demonstrated superiority compared to placebo for major cardiovascular events (MACE).
Methods: We update and discuss their impact on MACE expressed as relative risk (HR hazard ratio) and as the number needed to treat (NNT) to avoid one cardiovascular event in 5 years. We include the publications of the last 10 years. Results: Empagliflozin, Canagliflozin and Dapagliflozin present an HR for MACE of 0.86, 0.86, 0.86 and an NNT of 38, 44, and 33, respectively (Dapagliflozin in secondary prevention). Regarding HHF (Hospitalization for Heart Failure), the HR was 0.65, 0.67, 0.73 and NNT was 44, 62, and 98, respectively. Lixisenatide, Exenatide, Liragutide, Semaglutide, Albiglutide and Dulaglutide presented for MACE an HR of 1.02, 0.91, 0.87, 0.74, 0.78, 0.88, respectively. There was no increase in the risk of HHF, but there was no benefit either. Conclusion: Cardiovascular benefits of the GLP-1RA and the SGLT2i are clinically significant. A number needed to treat under 50 is required to avoid one MACE in five years. These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM. Keywords: Cardiovascular outcomes, glucose lowering medications, type 2 diabetes mellitus, SGLT2i, GLP1 agonist, cardiovascular mechanisms, cardiovascular disease.
Vuodelta 2020 ( Semaglutide , dulaglutide, exenatide, liraglutide, lixisenatide)
https://pubmed.ncbi.nlm.nih.gov/31990244/
J Med Econ 2020 Jun;23(6):650-658.
doi: 10.1080/13696998.2020.1722678. Epub 2020 Feb 7. Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis B B Hansen 1 , S Nuhoho 1 , S N Ali 2 , T Dang-Tan 2 , W J Valentine 3 , S J P Malkin 3 , B Hunt 3 DOI: 10.1080/13696998.2020.1722678 Free article Results: For the treatment target of HbA1c ≤6.5%, once-weekly semaglutide 1 mg and oral semaglutide 14 mg were associated with the lowest costs of control, at USD 15,430 and USD 17,383 per patient achieving target, respectively. Similarly, the cost of control was lowest with once-weekly semaglutide 1 mg at USD 12,627 per patient achieving target, followed by oral semaglutide 14 mg at USD 13,493 per patient achieving target for the target of HbA1c <7.0%. All other interventions were associated with higher cost of control values for both targets. Conclusions: Oral semaglutide 14 mg is likely to be cost-effective versus dulaglutide, exenatide (once weekly and twice daily), liraglutide, and lixisenatide in terms of bringing people with type 2 diabetes to glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0% in the US.
(Bacground: Clinicians have a range of treatment options available to treat people with type 2 diabetes not achieving glycemic control on metformin monotherapy, including modern interventions such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and older interventions such as thiazolidinediones and sulfonylureas1. GLP-1 receptor agonists are recommended when there is a need to minimize the risk of hypoglycemia, and when there is a need to minimize weight gain or promote weight loss1. Furthermore, GLP-1 receptor agonists with a proven positive impact on the risk of cardiovascular disease are preferred for treatment of patients at high risk of cardiovascular disease1. )
Vuodelta 2020 (lixisenatide)
Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats
2020, Life Sciences
https://www.sciencedirect.com/science/article/abs/pii/S002432052031345X
Lixisenatide, in a low dose regimen, induced a nephroprotective effect evident by significant decreases in serum creatinine and serum urea along with improved renal histology. Low lixisenatide dose showed an antioxidant effect, exhibited by a significant decrease in renal malondialdehyde and total NOx− levels along with a marked rise in total antioxidant capacity. Apart from ameliorating glucose intolerance and insulin resistance, significant down-regulation in renal expressions of iNOS, COX-2, and TGF-B1 were recorded in the diabetic group treated with low dose lixisenatide. Furthermore, low dose lixisenatide was reported to be superior to glimepiride as a nephroprotective. On the contrary, treatment with large dose lixisenatide was founded to be deleterious.
Vuodelta 2019 kuva (liraglutide, semaglutide)
Figure: GLP-1, liraglutide, semaglutide:
Vuodelta 2019: Obes Rev 2019 Jun;20(6):805-815.
Epub 2019 Feb 15. Semaglutide as a promising antiobesity drug Georgios A Christou 1 et al. DOI: 10.1111/obr.12839 https://pubmed.ncbi.nlm.nih.gov/30768766/ Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.
Vuodelta 2019 (liraglutide, semaglutide)
The Discovery and Development of Liraglutide and Semaglutide. Knudsen LB, Lau J. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. eCollection 2019. PMID: 31031702 Free PMC article. Review. Furthermore, the development of an oral formulation for semaglutide may provide individuals with additional benefits in relation to treatment adherence. In addition to T2D, liraglutide is used in the treatment of obesity, while semaglutide is currently under investi …
Vuodelta 2018 ( GLP-1RAs, insulin combination)
Am J Med 2018 Nov;131(11):1304-1306.
doi: 10.1016/j.amjmed.2018.05.043. Epub 2018 Jul 2. New Injectable Agents for the Treatment of Type 2 Diabetes Part 2-Glucagon-Like Peptide-1 (GLP-1) Agonists Christa George 1 , AhYoung Byun 2 , Amanda Howard-Thompson 3 Affiliations DOI: 10.1016/j.amjmed.2018.05.043 Abstract The US Food and Drug Administration has recently approved several new glucagon-like peptide-1 (GLP-1) agonists alone and in combination with various insulin products. The second of 2 articles in a series, this review will describe the potential advantages and disadvantages of the GLP-1 agonist class of products. Keywords: GLP-1 combination products; Glucagon like peptide-1 (GLP-1) agonist; Type 2 diabetes.
Vuodelta 2016 (exenatide, albiglutide, dulaglutide, liraglutide, lixisenatid)
Vuodelta 2015 informaatiota ruotsalaisesta diabeteslääkehoidon arsenaalista: Mikael Ry´den :Inkretinläkemedel- dyra med oklara läkemedeleffekter (Sida 67) “Det senaste tillskottet I den terapeutiska arsenalen är preparat som påverkar inkretinsystemet. Glukagonlik peptid 1 (GLP-1) är den fysiologiskt kanske viktigaste inkretinen, som verkar genom att öka insulinfrisättningen på intracellulära steg nedom sulfonylureapreparat (SU). Det innebär bl a att GLP-1 stimulerar insulinfrisättningen endast vid förhöjda glukosvärden. Antingen kan man ge subkutana injektioner av GLP-1-analoger (exanatide, liraglutide etc. ) eller perorala preparat som hämmar enzymet dipeptidylpeptidas-4 (DPP4) (sitagliptin etc.) , som bryter ned endogent GLP-1 HbA1c sänks med ca 1 procentenhet med GLP-1-analoger och med 0,7 procentenheter med DPP4-hämmare. GLP-1-analoger förlångsammar även ventrikeltömmningen och kan eventuellt ha effekter på centrala mättnadssystemet. Illamående är vanlig biverkan, men för de patienter som föredrar behandlingen innebär behandlingen med GLP-1-analoger ofta viktnedgång. I kliniska studier har man observerat en viktminskning på ca 3 kg under sex månader, men hos enskilda individer kan effekten vara både större och mindre. DPP-4 hämmare (-gliptiner) är viktneutrala. Det finns ännu inga långtidsstudier på något av dessa preparat, och de är väsentligt dyrare än övriga läkemedel, varför de bör användas restriktivt. Följaktligen bör de betraktas som tredjehandspreparat (prioritet 10 enligt Socialstyrelsen) . En lämplig patient för GLP-1-analoger kan t ex vara en kraftigt obes patient med postprandiala hyperglykemier, där insulin lett eller förväntas leda till utttalada viktuppgång, som kan innebära medicinsk risk. DPP4-hämmare kan övervägas hos patienter som behöver tillägg av perorala antidiabetik men som reagerar med hypoglykemier även på låga elelr måttiga doser av sulfonyureapreparat(SU). Det är viktigt att med dessa nya och dyra preparat utvärdera effekten efter 3-6 månader och seponera preparatet vid utebliven eller otillräcklig effekt.
Vuodelta 2015 (exenatide)
Epub 2015 Nov 11. The value of short- and long-acting glucagon-like peptide-1 agonists in the management of type 2 diabetes mellitus: experience with exenatide
DOI: 10.1185/03007995.2015.1103214 AbstractBackground: Only about half of patients with type 2 diabetes treated with antihyperglycemic drugs achieve glycemic control (HbA1c <7%), most commonly due to poor treatment adherence. Glucagon-like peptide-1 (GLP-1) receptor agonists act on multiple targets involved in glucose homeostasis and have a low risk of causing hypoglycemia. While GLP-1 receptor (GLP-1R) agonists (GLP-1RA) share the same mechanism of action, clinical profiles of individual agents differ, particularly between short- and long-acting agents.
In this article, recent findings regarding the pharmacology of GLP-1 agonists are reviewed, and the clinical effects of short- versus long-acting agents are compared.Data sources: Relevant articles were identified through a search of PubMed using the keywords glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor agonist, GLP-1R agonist, and exenatide for publications up to 22 May 2015. Supporting data were obtained from additional searches for e as well as from the bibliographies of key articles.Findings: Short-acting GLP-1R agonists produce greater reductions in postprandial glucose levels by slowing gastric emptying, whereas long-acting GLP-1R agonists produce greater reductions in fasting blood glucose by stimulating insulin secretion from the pancreas. These characteristics can be exploited to provide individualized treatment to patients. A large body of evidence supports the benefits of short- and long-acting exenatide as add-on therapy in patients with inadequate glycemic control despite maximum tolerated doses of metformin and/or sulfonylurea. Exenatide is generally well tolerated and no new safety concerns were identified during long-term follow-up of up to 5 years. A limitation of this review of short-and long-acting GLP-1 receptor agonists is that it focuses on exenatide rather than all the drugs in this class. However, the focus on a single molecule helps to avoid any confusion that may be introduced as a result of differences in molecular structure and size.Conclusions: Short-acting GLP-1R agonists including exenatide are well suited to patients with type 2 diabetes with exaggerated postprandial glucose excursions and for co-administration with basal insulin therapy. Long-acting GLP-1R agonists including once weekly exenatide offer greater convenience and are well suited to patients who require specific control of fasting hyperglycemia.Vuodelta 2014 (GLP1 reseptoriagonisti- insuliini-kombinaatio)
Insulin and glucagon-like peptide receptor agonist (GLP 1 RA) combinations. Kalra S. J Pak Med Assoc. 2014 Mar;64(3):359-61. PMID: 24864619 Review.
Vuodelta 2013 (lixisenatide , exenatide )
Rosenstock J .Raccah D ,Koranyi L et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin (Get Goal-X).Diabetes Care. 2013; 36: 2945-2951
- Vuodelta 2012 (exenatide, liraglutide)
(Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives). Clinical efficacy and safety of once-weekly glucagon-like peptide-1 agonists in development for treatment of type 2 diabetes mellitus in adults. Tzefos M, Harris K, Brackett A. Ann Pharmacother. 2012 Jan;46(1):68-78. doi: 10.1345/aph.1Q379. PMID: 22232377 Review.
Vuodelta 2012 (Liraglutide)
.2012 Oct;28(4):436-44.
doi: 10.1017/S0266462312000608. Epub 2012 Sep 24. Cost-utility analysis of liraglutide versus glimepiride as add-on to metformin in type 2 diabetes patients in ChinaVuodelta 2011 (Liraglutide, exenatide)
https://pubmed.ncbi.nlm.nih.gov/21609656/
Liraglutide for the treatment of type 2 diabetes D Shyangdan 1 , E Cummins, P Royle, N Waugh Affiliations DOI: 10.3310/hta15suppl1/09 Health Technol Assess 2011 May;15 Suppl 1:77-86. doi: Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon.
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