2022. One of the meta-analyses showed that SGLT2 inhibitors were associated with a significantly lower risk of atrial arrhythmias and a risk of sudden cardiac death in patients with type 2 diabetes and heart failure [, Gliflozins can also be used in the treatment of obesity. Sfairopoulos, D.; Zhang, N.; Wang, Y.; Chen, Z.; Letsas, K.P. 12 2021 Vol. The site is secure. Only a few years ago, lifestyle modification, sulfonylureas, metformin, and insulin were the only treatment options for type 2 diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a long history, which began with the isolation of phlorizin from apple tree bark and hence the name of the group (gliflozins). ; Zafar, M.U. 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Packer, M.; Anker, S.D. Despite that around half of the SGLT2-i- and the GLP1-RA users discontinued therapy (for at least 90 days), almost a quarter reinitiated therapy shortly after, indicating that a large proportion of the patients only discontinued temporarily. ; Terres, W.; Seyfarth, M.; Schultheiss, H.-P.; Richardt, G.; Sheehan, F.H. The ketone metabolite -hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Uthman, L.; Baartscheer, A.; Schumacher, C.A. ; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. ; Lewis, J.B.; Ritz, E.; Atkins, R.C. Voros, G.; Ector, J.; Garweg, C.; Droogne, W.; Van Cleemput, J.; Peersman, N.; Vermeersch, P.; Janssens, S. Increased Cardiac Uptake of Ketone Bodies and Free Fatty Acids in Human Heart Failure and Hypertrophic Left Ventricular Remodeling. The content on this site is intended for healthcare professionals. 8 2017 Vol. Morten Schou: reports lecture fees from Novartis, Boehringer-Ingelheim, Astra Zeneca and Novo Nordisk. A total of 77,745 first-time users of SGLT2-is (64% male, median age 64 [interquartile range 5672]) and 56,037 first-time users of GLP1-RAs (56% male, median age 61 [5370]) were included. ; Leiter, L.A.; McGuire, D.K. ; Hattersley, A.T.; Jones, A.G.; Dennis, J.M. A differential volume regulation hypothesis. Weight loss variability with SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes mellitus and obesity: Mechanistic possibilities. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. ; Blohlvek, J.; et al. Another notable observation in our study was the improved persistence with both drugs, respectively, over the study period. ; Ponikowski, P.; DeMets, D.L. ; Broedl, U.C. ; Tse, G.; Li, G.; Lip, G.; Liu, T.; Korantzopoulos, P. Association between sodium-glucose cotransporter-2 inhibitors and risk of sudden cardiac death or ventricular arrhythmias: A meta-analysis of randomized controlled trials. Topics include etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications such as nephropathy. Lecture fees/manuscript writing for Abbott Laboratories, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk. Aubert, G.; Martin, O.J. 25 Issue 3 CURRENT ISSUE pp.157-216 February 2023 Vol. ; Baumbach, A.; Bhm, M.; Burri, H.; Butler, J.; elutkien, J.; Chioncel, O.; et al. krti, M.; Cherney, D.Z. Factors associated with discontinuation of GLP1-RA. No other diabetes medication excels in the STEPS criteria as well as metformin. ; McMurray, J.J.V. Historical concern for lactic acidosis, but Cochrane review of 347 studies found no cases in 70,490 patient-years, with lactate levels similar between patients receiving metformin (Glucophage) and a control group, GI effects (e.g., diarrhea, nausea, vomiting) in <10% of patients; discontinuation rate is <1%, Twice-daily oral dosing (once daily for extended-release formulation), Glipizide: $5 ($50 to $100, depending on dosage), Once- or twice-daily oral dosing (depending on dosage; once daily for extended-release formulation), Hypoglycemia, worse with intensive or complicated regimens, Subcutaneous injections one to four times daily, depending on formulation. As HF progresses, the activity of enzymes involved in mitochondrial fatty acid oxidation decreases. Around half of all SGLT2-i and GLP1-RA users discontinued therapy, temporary or permanent, during the first five years of therapy with a significant improvement in the persistence over the years. Of the SGLT2-i users, 14,691 were excluded because of age <40 years or type 1 diabetes. Factors associated with discontinuation of SGLT2-i. Throughout the study, patients were followed from index date until emigration, death, or end of study period (December 31, 2021), whichever occurred first. Journal List Diabetes Ther Diabetes Therapy Vols. The index date was defined as the date of first redeemed prescription of a SGLT2-i in the SGLT2-i cohort, and the date of first redeemed prescription of a GLP1-RA in the GLP1-RA cohort. The study protocol is available upon reasonable request via e-mail to the corresponding author. ; Powers, J.C.; Matsuura, T.R. "Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure" Journal of Cardiovascular Development and Disease 9, no. You are accessing a machine-readable page. Rapid publication: The journal aims for a 2-week peer review, 3-4 weeks from acceptance to online. Naveed Sattar: reports grants/contracts from Astra Zeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics. 2023 Springer Nature Switzerland AG. The study is approved by the Data Responsible Institute in the Capital Region of Denmark (approval number: P-2019-191). 2023 Springer Nature Switzerland AG. It is stressed that their diuretic effect may translate into a reduced need for loop diuretics. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Ansary, T.M. Additional subgroup analyses of the outcomes mentioned above, were performed in patients with and without cardiovascular disease (defined as heart failure, ischemic heart disease, acute myocardial infarction, peripheral artery disease, atrial fibrillation/flutter and stroke), in different calendar periods, in age groups and by sex. Research, treatment and education of diabetes and related disorders Diabetes Therapy Submission guidelines Submission guidelines Links and downloads Instructions for Authors (Download pdf, 510 kB) Author Information - Guidelines for digital features and plain language summaries (Download pdf, 359 kB) Open access publishing Fernandes, G.C. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. ; Leiter, L.A.; et al. Williams, S.M. However, it is possible that physicians prescribe injectable GLP1-RAs mainly to patients they perceive to be the most compliant, as the administration and dosage for this form of treatment is more complex compared to the daily tablet of SGLT2-is with no titration period or regular follow-up. Fitchett, D. A safety update on sodium glucose co-transporter 2 inhibitors. ; Hare, G.M. (1.0%) there is a greater probability that insulin therapy will be initiated, but when HbA1c gap is <6.6 mmol/mol (0.6%), a timely initiation of insulin therapy is less probable . The absolute five-year risk of discontinuing SGLT2-i therapy was 56% (95% CI: 5557) and the absolute five-year risk of discontinuing GLP1-RA therapy was 45% (4546) (, In SGLT2-i users, the presence of heart failure, atrial fibrillation and hypertension were all associated with a significantly lower rate of discontinuing therapy (, In total, 28,639 SGLT2-i users and 15,462 GLP1-RA users discontinued therapy over a five-year period and were included in the analyses. Patients were considered in therapy until 90 days after the estimated medication coverage period of the last refilled prescription, to avoid conditioning on future events. Inclusivity:All scientifically sound research considered be it positive, confirmatory or negative data. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. April 2019, issue 2. ; Ibrahim, N.E. ; Cannon, C.P. Bhatt, D.L. Mediators of the Effects of Canagliflozin on Heart Failure in Patients with Type 2 Diabetes. Author disclosure: No relevant financial affiliations. Submitted manuscripts can report any aspect of laboratory, animal, or human research. No . An extract of gymnema leaf, called GS4, has been studied as an adjuvant therapy to conventional care in two controlled, nonrandomized trials of patients with type 1 and type 2 diabetes, respectively. SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models. Mark C. Petrie: reports grants/contracts from Boehringer Ingelheim, Roche, SQ Innovations, Astra Zeneca, Novartis, Novo Nordisk, Pharmacosmos, and consulting fees from Boehringer Ingelheim, Novartis, Astra Zeneca, Novo Nordisk, Abbvie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, Vifor. Editors Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Seferovi, P.M.; Fragasso, G.; Petrie, M.; Mullens, W.; Ferrari, R.; Thum, T.; Bauersachs, J.; Anker, S.D. ; Malnic, G.; Girardi, A.C.C. Accepted: The absolute one-year probability of reinitiating therapy was 24% (95% CI: 2425) for SGLT2-i users and 26% (2527) for GLP1-RA users. If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. Since the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2-i) in 2013 and glucagon-like peptide-1 receptor agonists (GLP-1RA) in 2006 for the treatment of type 2 diabetes (T2D), both agents have come a long way proving to have beneficial effects in a broad spectrum of diseases. The patterns of discontinuation and reinitiation of SGLT2-is and GLP1-RAs among patients with T2D were very similar and was comparable to the discontinuation of other cardioprotective drugs (metformin, statins, and RAS-inhibitors). Common ground on dietary approaches for the prevention, management, and potential remission of type 2 diabetes can be found, argue Nita G Forouhi and colleagues Dietary factors are of paramount importance in the management and prevention of type 2 diabetes. Avoid the most common mistakes and prepare your manuscript for journal editors. Therapy with SGLT2 inhibitors should be continued as they slow down the deterioration of renal function in the long-term follow-up. Major guidelines are increasingly aligned with a STEPS approach to pharmacotherapy for type 2 diabetes. Cumulative incidence plots for reinitiating therapy are illustrated in, Of the 28,639 SGLT2-i users and the 15,462 GLP1-RA users that discontinued therapy during the study period, 36% (10,310) and 40% (6185), respectively, had at least one hospitalization (>24h) within 3 months prior to discontinuation (, The absolute five-year risks of discontinuing metformin, statins, and RAS inhibitors, respectively, in all first-time users >40 years at the same time-period (20132021) were also calculated and presented in, Defining discontinuation of therapy as a gap of. Contact:For more information about the journal, including pre-submission enquiries, please contact Charley Lai: charley.lai@springer.com. Foreign researchers can apply for access to the data through an affiliation to an authorized Danish research environment. Dapagliflozin in patients with heart failure and reduced ejection fraction. ; Woerle, H.J. Copyright 2023 American Academy of Family Physicians. ; Brandimarto, J.; Aziz, M.; Mesaros, C.; Worth, A.J. Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Denmark, Department of Cardiology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. Data through an affiliation to an authorized Danish research environment to the through... 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