Coexistence of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of a patient with type 2 diabetes mellitus
Authors:
Piotr Waszczuk
Authors‘ workplace:
Diabetologická ambulancia UNsP Milosrdní bratia, spol. s r. o., Bratislava
Published in:
Diab Obez 2024; 24(1): 41-50
Category:
Reviews
Overview
The ADA/EASD recommendations are increasing the importance of the use of GLP-1 receptor agonists (GLP1-RA) and SGLT2 inhibitors (SGLT2i) in the treatment of type 2 diabetes mellitus. In patients already treated with GLP1-RA, the addition of SGLT2i with a proven cardiovascular benefit should be considered, or vice versa. The importance of the coexistence of SGLT2i and GLP1-RA, and their potential and additive effects in treatment has been pointed out by several studies, and addressed by several authors in their papers. The SUSTAIN 9 study and the ADWARD 10 study, both randomized, double-blind, placebo-controlled, multicentre and international trials, point to the significant metabolic effects of the combination of GLP1-RA and an SGLT2i and their importance in the treatment of type 2 diabetes mellitus. The coexistence of SGLT2 and GLP1-RA, and the complementary mechanisms of action of SGLT2i and GLP1-RA, yield cardio-renal-metabolic effects in the treatment of patients with type 2 diabetes mellitus. The current indication limitations expand the possibilities for the use of GLP1-RA and SGLT2i in therapeutic modalities. The coexistence of SGLT2i and GLP1-RA for outpatient practice is schematically illustrated and described in a step-by-step time sequence in the pictorial appendix. The combination of SGLT2i and GLP1-RA in fixed combination with basal insulin provides the possibility of influencing the pathophysiological mechanisms of the so-called “ominous octet”.
Keywords:
fixed combination – basal insulin – ADWARD 10 – cardio-renal-metabolic effects – coexistence of SGLT2i and GLP-1 RA – SUSTAIN 9
Sources
ElSayed NA, Grazia Aleppo G, Vanita R. Aroda VR et al. [American Diabetes Association]. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023. Diabetes Care 2023; 46(Suppl 1): S140–S157. Dostupné z DOI: <http://dx.doi.org/https://doi.org/10.2337/dc23-S009>.
Ministerstvo zdravotníctva Slovenskej republiky. Zoznam kategorizovaných liekov 1.3.2024 – 31.3.2024, Časť B: Indikačné obmedzenia. Dostupné z WWW: <https://www.health.gov.sk/Clanok?lieky202403>.
DeFronzo RA, Eldor R, Abdul-Ghani M et al. Pathophysiologic approach to therapy in patients with newly diagnosedtype 2 diabetes. Diabetes Care 2013; 36(Suppl 2): S127-S138. Dostupné z DOI: <http://dx.doi.org/10.2337/dcS13–2011>.
Waszczuk P. Fixná kombinácia inzulínu glargín a GLP-1 antagonistu lixisenatidu iGlarLixi – deintenzifikácia, titrácia a zlepšenie metabolickej kompenzácie pacienta s diabetes mellitus 2. typu. Dostupné z WWW: <https://www.m-edu.sk/fixna-kombinacia-inzulinu-glargin-a-glp-1-antagonistu-lixisenatidu-iglarlixi-deintenzifikacia-titracia-a-zlepsenie-metabolickej-kompenzacie-pacienta-s-diabetes-mellitus-2-typu/>.
DeFronzo RA. Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 2017; 19(10): 1353–1362. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12982>.
Gourdy P, Darmon P, Dievart F et al. Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM). Cardiovasc Diabetol 2023; 22(1): 79. Dostupné z DOI: <https://doi.org/10.1186/s12933–023–01798–4>.
Anderson JE. Combining Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors to Target Multiple Organ Defects in Type 2 Diabetes. Diabetes Spectr 2020; 33(2): 165–174. Dostupné z DOI: <https://doi.org/10.2337/ds19–0031>.
Frías JP, Guja C, Elise Hardy E et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 2016; 4(12): 1004–1016. Dostupné z DOI: <https://doi.org/10.1016/S2213–8587(16)30267–4>.
DeFronzo RA. Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 2017; 19(10) :1353–1362. Dostupné z DOI: <https://doi.org/10.1111/dom.12982>.
Díaz-Trastoy O, Villar-Taibo R, Sifontes-Dubón M et al. GLP1 receptor agonist and SGLT2 inhibitor combination: an effective approach in real-world clinical practice. Clin Ther 2020; 42(2): e1–e12. Dostupné z DOI: <http://dx.doi.org/10.1016/j.clinthera.2019.12.012>.
Goldenberg RM, Ahooja V, Clemens KK et al. Practical considerations and rationale for glucagon-like peptide-1 receptor agonist plus sodium-dependent glucose cotransporter-2 inhibitor combination therapy in type 2 diabetes. Can J Diabetes 2021; 45(3): 291–302. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jcjd.2020.09.005>.
Packer M. Critical reanalysis of the mechanisms underlying the cardiorenal benefits of SGLT2 inhibitors and reaffirmation of the nutrient deprivation signaling/autophagy hypothesis. Circulation 2022; 146(18): 1383–1405. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.122.061732>.
Bertoccini L, Baroni MG. GLP-1 receptor agonists and SGLT2 inhibitors for the treatment of type 2 diabetes: new insights and opportunities for cardiovascular protection. Adv Exp Med Biol 2021; 1307: 193–212. Dostupné z DOI: <http://dx.doi.org/10.1007/5584_2020_494>.
Lo CWH, Fei Y, Cheung BMY. Cardiovascular outcomes in trials of new antidiabetic drug classes. Card Fail Rev 2021; 7: e04. Dostupné z DOI: <http://dx.doi.org/10.15420/cfr.2020.19>.
Koyani CN, Plastira I, Sourij H et al.Empagliflozin protects heart from inflammation and energy depletion via AMPK activation. Pharmacol Res 2020; 158:104870. Dostupné z DOI: <http://doi: 10.1016/j.phrs.2020.104870>.
Iannantuoni F, de Aranzazu MM, Diaz-Morales N et al.The SGLT2 inhibitor Empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes. J Clin Med 2019; 8(11): 1814. Dostupné z DOI: <http://doi: 10.3390/jcm8111814>.
Nauck MA, Quast DR, Wefers J et al. GLP-1 receptor agonists in the treatment of type 2 diabetes—state-of-the-art. Mol Metab 2021; 46: 101102. Dostupné z DOI: <http://dx.doi.org/10.1016/j.molmet.2020.101102>.
Zinman B, Bhosekar V, Busch R et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2019; 7(5): 356–367. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30066-X>.
SPC Ozempic. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/ozempic-epar-product-information_sk.pdf>.
Ludvik B, Frías JP, Tinahones FJ et al. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2018; 6(5): 370–381. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(18)30023–8>.
SPC Trulicity. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/trulicity-epar-product-information_sk.pdf>.
Guo M, Gu J, Teng F et al. The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis. Endocrine 2020; 67(2): 294–304. Dostupné z DOI: <http://dx.doi.org/10.1007/s12020–019–02175–6>.
SPC Xultophy. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/xultophy-epar-product-information_sk.pdf>.
SPC Suliqua. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/suliqua-epar-product-information_sk.pdf>.
SPC Jardiance. Dostupné z WWW: <https://www.ema.europa.eu/sk/documents/product-information/jardiance-epar-product-information_sk.pdf>.
SPC Invokana. Dostupné z WWW: <https://www.ema.europa.eu/sk/documents/product-information/invokana-epar-product-information_sk.pdf>.
SPC Forxiga. Dostupné z WWW: <https://www.ema.europa.eu/sk/documents/product-information/forxiga-epar-product-information_sk.pdf>.
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Diabetology ObesitologyArticle was published in
Diabetes and obesity
2024 Issue 1
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