The current role of gliptins in the management of type 2 diabetic patients
Authors:
Ubomíra Fábryová
Authors‘ workplace:
MetabolKLINIK s. r. o., Ambulancia pre diabetológiu, poruchy látkovej premeny a výživy, MED PED centrum, Bratislava
1; Biomedicínske centrum Slovenskej Akadémie Vied, Bratislava
2; Vysoká škola zdravotníctva a sociálnej práce sv. Alžbety, Inštitút prevencie a intervencie, Bratislava
3
Published in:
Forum Diab 2022; 11(3): 129-134
Category:
Review Article
Overview
The current philosophy of antidiabetic treatment in type 2 diabetic patients is based on recently published results of clinical studies aimed at testing cardiocerebrovascular and renal morbidity and mortality and the safety of newer drugs for the treatment of type 2 diabetes mellitus. The new therapeutic recommendations of the Slovak Diabetes Association and the Slovak Diabetes Society published in 2021 detail the hierarchy of therapeutic groups as they should be used in clinical practice in the continuity of current knowledge. Metformin remains the first choice. GLP-1 RAs (glucagon-like peptide-1 receptor agonists) and SGLT-2i (sodium-glucose cotransporter 2 inhibitors) are in the first preferred position of choice with metformin. We prefer these groups of pharmaceuticals not only because of the significant improvement in glycemic compensation, low risk of hypoglycemia and beneficial effect on weight reduction, but mainly because of the confirmed cardiovascular, cerebrovascular and renal benefits. In case of intolerance or contraindication to GLP-1 RA or SGLT-2i, cardiovascular neutral DPP-4 inhibitors (dipeptidyl peptidase- 4 inhibitors) are listed in second place (sitagliptin, linagliptin). DPP-4 inhibitors are important oral antidiabetic agents that have no risk of hypoglycemia and are weight neutral. They should be used as second-line therapy to metformin in type 2 diabetics without pre-existing cardiovascular disease. DPP-4 inhibitors can also be administered in a triple combination with metformin and SGLT-2 inhibitors or with metformin and insulin. Combination with GLP-1 RA is not recommended because DPP-4 inhibitors as well as GLP-1 RA increase plasma concentrations of GLP-1. The side effect profile of DPP-4 inhibitors is favorable, there are few treatment-limiting adverse events, and DPP-4 inhibitors have demonstrated cardiovascular safety. Another favorable characteristic of DPP-4 inhibitors is their efficacy and safety profile in patients with impaired renal function.
Keywords:
DPP-4 inhibitors – linagliptin – sitagliptin – alogliptin – CARMELINA – CAROLINA – EXAMINE – Savor-TIMI-53 – saxagliptin – TECOS – therapeutic algorithm – vildagliptin
Sources
1. IDF. Estimated number of people with diabetes worldwide per region (20–79 years) in 2019. International Diabetes Federation (IDF) Diabetes Atlas. 9th ed. IDF: Brussels, Belgium 2019. Dostupné z WWW: <https://diabetesatlas.org/en/resources/>.
2. Činnosť diabetologických ambulancií v Slovenskej republike 2020. NCZI 2021. Dostupné z WWW: <https://www.nczisk.sk/Statisticke_vystupy/Tematicke_statisticke_vystupy/Diabetologia>.
3. Draznin B, Aroda VR, Bakris G. [American Diabetes Association Professional Practice Committee]. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes – 2022. Diabetes Care 2022; 45(Suppl 1): S125–S143. Dostupné z DOI: <https://doi.org/10.2337/dc22-S009>.
4. Martinka E, Tkáč I, Mokáň M et al. 2021 Konsenzuálne odporúčania Slovenskej diabetologickej asociácie (SDiA) a Slovenskej diabetologickej spoločnosti (SDS) pre liečbu diabetes mellitus 2. typu. Forum Diab 2021; 10(Suppl 2): 43–76.
5. Gallwitz B. Clinical Use of DPP-4 Inhibitors. Front Endocrinol (Lausanne) 2019; 10: 389. Dostupné z DOI: <http://dx.doi.org/10.3389/fendo.2019.00389>.
6. Monami M, Vitale V, Ambrosio ML et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther 2012; 29(9):736–746. Dostupné z DOI: <http://dx.doi.org/10.1007/s12325–012–0045–5>.
7. Fábryová Ľ. Antiaterogénny efekt inkretínov: fakt alebo fikcia? Interná Med 2014; 14(2): 77–82.
8. Almagthali AG, Alkhaldi EH, Alzahrani AS et al. Dipeptidyl peptidase-4 inhibitors: antidiabetic drugs with potential effects on cancer. Diabetes Metab Syndr 2019; 13(1): 36–39. Dostupné z DOI: <http://dx.doi.org/10.1016/j.dsx.2018.08.012>.
9. Kawaguchi Y, Shimauchi R, Nishibori N et al. Dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid: A retrospective study of 168 pemphigoid and 9,304 diabetes mellitus patients. J Diabetes Investig 2019: 10(2): 392–398. Dostupné z DOI: <http://dx.doi.org/10.1111/jdi.12877>.
10. Tkáč I, Raz I. Combined analysis of three large interventional trials with gliptins indicates increased incidence of acute pancreatitis in patients with type 2 diabetes. Diabetes Care 2017; 40(2): 284–286. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1707>.
11. White WB, Cannon CP, Heller SR et al. [EXAMINE Investigators]. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013: 369(14): 1327–1335. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1305889>.
12. Scirica BM, Bhatt DL, Braunwald E et al. [SAVOR-TIMI 53 steering committee and investigators]. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013: 369(14): 1317–1326. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1307684>.
13. Green JB, Bethel MA, Armstrong PW et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373(1): 232–242. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1501352>.
14. Rosenstock J, Perkovic V, Johansen OE et al. [CARMELINA investigators]. Effect of linagliptin vs placebo on major cardiovascular events in adults with Type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA 2019: 321(1): 69–79. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2018.18269>.
15. Rosenstock J, Kahn SE, Johansen OE et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA 2019; 322(12): 1155–1166. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2019.13772>.
16. Fábryová Ľ. Diabetes Mellitus a obezita (Diabezita) a COVID-19. Forum Diab 2022; 11(1): 15–23.
17. Popovic DS, Papanas N, Stoian AP et al. Use of Novel Antidiabetic Agents in Patients with Type 2 Diabetes and COVID-19: A Critical Review. Diabetes Ther 2021; 12(12): 3037–3054. Dostupné z DOI: <https://doi.org/10.1007/s13300–021–01170–3>.
18. Katsiki N, Ferrannini E. Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era? J Diabetes Complications 2020; 34(12):107723. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jdiacomp.2020.107723>.
19. [WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection]. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20(8): e192–e197. Dostupné z DOI: <http://dx.doi.org/10.1016/S1473–3099(20)30483–7>.
20. Popovic DS, Papanas N, Stoian AP et al. Use of Novel Antidiabetic Agents in Patients with Type 2 Diabetes and COVID-19: A Critical Review. Diabetes Ther 2021; 12(12): 3037–3054.Dostupné z DOI: <http://dx.doi.org/https://doi.org/10.1007/s13300–021–01170–3>.
21. Katsiki N, Ferrannini E. Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era? J Diabetes Complications 2020; 34(12): 107723. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jdiacomp.2020.107723>.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Forum Diabetologicum
2022 Issue 3
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