Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials

Mansoor Husain, Stephen C Bain, Anders Gaarsdal Holst, Thomas Mark, Søren Rasmussen, Ildiko Lingvay, Mansoor Husain, Stephen C Bain, Anders Gaarsdal Holst, Thomas Mark, Søren Rasmussen, Ildiko Lingvay

Abstract

Background: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog treatment for type 2 diabetes (T2D) available in subcutaneous (s.c.) and oral formulations. Two cardiovascular (CV) outcomes trials showed that in subjects with T2D at high risk of CV events there were fewer major adverse CV events (MACE; defined as CV death, non-fatal stroke, non-fatal myocardial infarction) with semaglutide than with placebo (hazard ratio [95% CI]: 0.74 [0.58;0.95] for once-weekly s.c. semaglutide and 0.79 [0.57;1.11] for once-daily oral semaglutide). However, there is little evidence for an effect of semaglutide on MACE in subjects not at high risk of CV events. This post hoc analysis examined CV effects of semaglutide in subjects across a continuum of baseline CV risk.

Methods: Data from the s.c. (SUSTAIN) and oral (PIONEER) semaglutide phase 3a clinical trial programs were combined according to randomized treatment (semaglutide or comparators) and analyzed to assess time to first MACE and its individual components. A CV risk model was developed with independent data from the LEADER trial (liraglutide vs placebo), considering baseline variables common to all datasets. Semaglutide data were analyzed to assess effects of treatment as a function of CV risk predicted using the CV risk prediction model.

Results: The CV risk prediction model performed satisfactorily when applied to the semaglutide data set (area under the curve: 0.77). There was a reduced relative and absolute risk of MACE for semaglutide vs comparators across the entire continuum of CV risk. While the relative risk reduction tended to be largest with low CV risk score, the largest absolute risk reduction was for intermediate to high CV risk score. Similar results were seen for relative risk reduction of the individual MACE components and also when only placebo comparator data were included.

Conclusion: Semaglutide reduced the risk of MACE vs comparators across the continuum of baseline CV risk in a broad T2D population. Trial registrations ClinicalTrials.gov identifiers: NCT02054897, NCT01930188, NCT01885208, NCT02128932, NCT02305381, NCT01720446, NCT02207374, NCT02254291, NCT02906930, NCT02863328, NCT02607865, NCT02863419, NCT02827708, NCT02692716, NCT02849080, NCT03021187, NCT03018028, NCT03015220.

Keywords: Cardiovascular; MACE; Oral semaglutide; PIONEER; Risk prediction model; SUSTAIN; Subcutaneous semaglutide; Type 2 diabetes.

Conflict of interest statement

MH received advisory board fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novo Nordisk and Roche; research grants from AstraZeneca, Merck and Novo Nordisk; and speaker fees from Boehringer Ingelheim, Janssen and Novo Nordisk. SCB received honoraria fees, teaching and research grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi; funding for development of educational programs from Elsevier and Medscape; he also provided expert advice from All-Wales Medicines Strategy Group and National Institute for Health and Care Excellence (NICE) UK; and is a shareholder of Glycosmedia. AGH was a full-time employee of Novo Nordisk for the majority of manuscript development, and is a Novo Nordisk shareholder. TM was a full-time employee of Novo Nordisk for the majority of manuscript development, and is a Novo Nordisk shareholder. SM is an employee of Novo Nordisk and owns stock in the company. IL received grant support from Merck, Mylan, Novo Nordisk, Pfizer and Sanofi, personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Mannkind, Novo Nordisk, Sanofi, TARGETPharma and Valeritas; and non-financial support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Jannsen, Novo Nordisk, Pfizer and Sanofi.

Figures

Fig. 1
Fig. 1
Relative risk of MACE as a function of baseline CV risk and distribution of subjects. Hazard ratio for treatment effect (semaglutide vs comparator) and 95% CI estimated using a stratified Cox proportional hazards model including effects of treatment, CV risk score and interaction between both. The x-axis shows the CV risk score derived from subjects’ baseline characteristics in the semaglutide trials. Data on graph cut off at the 5th and 95th percentile of the whole dataset. Hazard ratio value of 1.00 is indicated by a horizontal dashed line. Underlying histograms: distribution of subjects in the glycemic efficacy trials or CVOTs across baseline CV risk scores (histogram data for 439 subjects not shown, as these subjects had a CV risk score of  0.0). CI confidence interval, CV cardiovascular, CVOT cardiovascular outcomes trial, HR hazard ratio, MACE major adverse cardiovascular events
Fig. 2
Fig. 2
Relative risk of each individual MACE component as a function of CV risk. Hazard ratios for treatment effect (semaglutide vs comparators) across all SUSTAIN and PIONEER trials analyzed. Hazard ratios (semaglutide vs comparators) and 95% CIs estimated using a stratified Cox proportional hazards model including effects of treatment, CV risk score and interaction between both. The x-axis shows the CV risk score derived from subjects’ baseline characteristics in the semaglutide trials. Data on graph cut off at the 5th and 95th percentile of the whole dataset. Hazard ratio value of 1.00 is indicated by a horizontal dashed line. CI confidence interval, CV cardiovascular, HR hazard ratio, MACE major adverse cardiovascular events, MI myocardial infarction
Fig. 3
Fig. 3
Estimated yearly risk of MACE as a function of CV risk. Absolute yearly MACE probabilities for semaglutide and comparators, respectively, estimated using a non-stratified Cox proportional hazards model including effects of treatment, CV risk score and interaction between both. The x-axis shows the CV risk score derived from subjects’ baseline characteristics in the semaglutide trials. Data on graph cut off at the 5th and 95th percentile of the whole dataset. CV cardiovascular, MACE major adverse cardiovascular events, NNT number needed to treat to avoid one MACE during 1 year

References

    1. Novo Nordisk. Ozempic® (semaglutide) Prescribing Information, 2020. . Accessed June 2020.
    1. Novo Nordisk. Rybelsus® (oral semaglutide) Prescribing information, 2020. . Accessed June 2020.
    1. Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015;58(18):7370–7380. doi: 10.1021/acs.jmedchem.5b00726.
    1. Buckley ST, Bækdal TA, Vegge A, Maarbjerg SJ, Pyke C, Ahnfelt-Rønne J, Madsen KG, Schéele SG, Alanentalo T, Kirk RK, et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med. 2018;10(467):eaar7047. doi: 10.1126/scitranslmed.aar7047.
    1. Granhall C, Donsmark M, Blicher TM, Golor G, Sondergaard FL, Thomsen M, Baekdal TA. Safety and pharmacokinetics of single and multiple ascending doses of the novel oral human GLP-1 analogue, oral semaglutide, in healthy subjects and subjects with type 2 diabetes. Clin Pharmacokinet. 2019;58(6):781–791. doi: 10.1007/s40262-018-0728-4.
    1. Hall S, Isaacs D, Clements JN. Pharmacokinetics and clinical implications of semaglutide: a new glucagon-like peptide (GLP)-1 receptor agonist. Clin Pharmacokinet. 2018;57(12):1529–1538. doi: 10.1007/s40262-018-0668-z.
    1. Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017;318(15):1460–1470. doi: 10.1001/jama.2017.14752.
    1. Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(4):251–260. doi: 10.1016/S2213-8587(17)30013-X.
    1. Ahrén B, Masmiquel L, Kumar H, Sargin M, Karsbol JD, Jacobsen SH, Chow F. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017;5(5):341–354. doi: 10.1016/S2213-8587(17)30092-X.
    1. Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2):258–266. doi: 10.2337/dc17-0417.
    1. Aroda VR, Bain SC, Cariou B, Piletič M, Rose L, Axelsen M, Rowe E, DeVries JH. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355–366. doi: 10.1016/S2213-8587(17)30085-2.
    1. Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu PL, Wijayasinghe N, Norwood P. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018;103(6):2291–2301. doi: 10.1210/jc.2018-00070.
    1. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–1844. doi: 10.1056/NEJMoa1607141.
    1. Kaku K, Yamada Y, Watada H, Abiko A, Nishida T, Zacho J, Kiyosue A. Safety and efficacy of once-weekly semaglutide versus additional oral antidiabetic drugs, in Japanese subjects with inadequately controlled T2D: a randomised trial. Diabetes Obes Metab. 2018;20(5):1202–1212. doi: 10.1111/dom.13218.
    1. Seino Y, Terauchi Y, Osonoi T, Yabe D, Abe N, Nishida T, Zacho J, Kaneko S. Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. Diabetes Obes Metab. 2018;20(2):378–388. doi: 10.1111/dom.13082.
    1. . Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes (SUSTAIN–CHINA MRCT). . Accessed June 2020.
    1. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275–286. doi: 10.1016/S2213-8587(18)30024-X.
    1. Lingvay I, Catarig AM, Frias JP, Kumar H, Lausvig NL, le Roux CW, Thielke D, Viljoen A, McCrimmon RJ. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7(11):834–844. doi: 10.1016/S2213-8587(19)30311-0.
    1. Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, Thrasher J, Woo V, Philis-Tsimikas A. 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. doi: 10.1016/S2213-8587(19)30066-X.
    1. Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S, Vergès B, Marre M. Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10) Diabetes Metab. 2020;46(2):100–109. doi: 10.1016/j.diabet.2019.101117.
    1. Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Morales Villegas EC, Jeppesen OK, Christiansen E, Hertz CL, Haluzik M. PIONEER 1: randomized clinical trial comparing the efficacy and safety of oral semaglutide monotherapy with placebo in patients with type 2 diabetes. Diabetes Care. 2019;42(9):1724–1732. doi: 10.2337/dc19-0749.
    1. Rodbard HW, Rosenstock J, Canani LH, Deerochanawong C, Gumprecht J, Lindberg S, Lingvay I, Søndergaard AL, Treppendahl MB, Montanya E, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: the PIONEER 2 trial. Diabetes Care. 2019;42(12):2272–2281. doi: 10.2337/dc19-0883.
    1. Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M, et al. Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. JAMA. 2019;321(15):1466–1480. doi: 10.1001/jama.2019.2942.
    1. Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, Pedersen KB, Saugstrup T, Meier JJ. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394(10192):39–50. doi: 10.1016/S0140-6736(19)31271-1.
    1. Mosenzon O, Blicher TM, Rosenlund S, Eriksson JW, Heller S, Hels OH, Pratley R, Sathyapalan T, Desouza C. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7(7):515–527. doi: 10.1016/S2213-8587(19)30192-5.
    1. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, Jeppesen OK, Lingvay I, Mosenzon O, Pedersen SD, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841–851. doi: 10.1056/NEJMoa1901118.
    1. Pieber TR, Bode B, Mertens A, Cho YM, Christiansen E, Hertz CL, Wallenstein SOR, Buse JB. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7(7):528–539. doi: 10.1016/S2213-8587(19)30194-9.
    1. Zinman B, Aroda VR, Buse JB, Cariou B, Harris SB, Hoff ST, Pedersen KB, Tarp-Johansen MJ, Araki E, Investigators P. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: the PIONEER 8 trial. Diabetes Care. 2019;42(12):2262–2271. doi: 10.2337/dc19-0898.
    1. Yamada Y, Katagiri H, Hamamoto Y, Deenadayalan S, Navarria A, Nishijima K, Seino Y. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020;8(5):377–391. doi: 10.1016/S2213-8587(20)30075-9.
    1. Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020;8(5):392–406. doi: 10.1016/S2213-8587(20)30074-7.
    1. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–322. doi: 10.1056/NEJMoa1603827.
    1. Kleinbaum DG, Klein M. Assessing discriminatory performance of a binary logistic model: ROC curves. In: Kleinbaum DG, Klein M, editors. Logistic Regression. New York, NY: Springer; 2010. pp. 345–387.
    1. Burnham KP, Anderson DR. Multimodel inference: understanding AIC and BIC in model selection. Sociol Methods Res. 2004;33(2):261–304. doi: 10.1177/0049124104268644.
    1. Raftery AE. Bayesian model selection in social research. Sociol Methodol. 1995;25:111–163. doi: 10.2307/271063.
    1. Husain M, Bain SC, Jeppesen OK, Lingvay I, Sørrig R, Treppendahl MB, Vilsbøll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020;22(3):442–451. doi: 10.1111/dom.13955.
    1. Giugliano D, Maiorino MI, Bellastella G, Longo M, Chiodini P, Esposito K. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019;21(11):2576–2580. doi: 10.1111/dom.13847.
    1. Hernandez AF, Green JB, Janmohamed S, D'Agostino RB, Sr, Granger CB, Jones NP, Leiter LA, Rosenberg AE, Sigmon KN, Somerville MC, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392(10157):1519–1529. doi: 10.1016/S0140-6736(18)32261-X.
    1. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Ryden L, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–130. doi: 10.1016/S0140-6736(19)31149-3.
    1. 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;3(6):844–857. doi: 10.1016/j.jacbts.2018.09.004.
    1. O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637–649. doi: 10.1016/S0140-6736(18)31773-2.
    1. Tanaka A, Node K. Clinical application of glucagon-like peptide-1 receptor agonists in cardiovascular disease: lessons from recent clinical cardiovascular outcomes trials. Cardiovasc Diabetol. 2018 doi: 10.1186/s12933-018-0731-y.
    1. Goncalves E, Bell DS. Efficacy of semaglutide versus liraglutide in clinical practice. Diabetes Metab. 2019;S1262-3636(19):30155–30157.
    1. Sposito AC, Berwanger O, de Carvalho LSF, Saraiva JFK. GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol. 2018;17(1):157. doi: 10.1186/s12933-018-0800-2.
    1. Vilsbøll T, Bain SC, Leiter LA, Lingvay I, Matthews D, Simo R, Helmark IC, Wijayasinghe N, Larsen M. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018;20(4):889–897. doi: 10.1111/dom.13172.
    1. Leiter LA, Bain SC, Hramiak I, Jódar E, Madsbad S, Gondolf T, Hansen T, Holst I, Lingvay I. Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovasc Diabetol. 2019;18(1):73. doi: 10.1186/s12933-019-0871-8.
    1. D'Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743–753. doi: 10.1161/CIRCULATIONAHA.107.699579.
    1. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991;121(1 Pt 2):293–298. doi: 10.1016/0002-8703(91)90861-B.
    1. Conroy RM, Pyörälä K, Fitzgerald AP, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetière P, Jousilahti P, Keil U, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003. doi: 10.1016/S0195-668X(03)00114-3.
    1. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) Eur Heart J. 2016;37(29):2315–2381. doi: 10.1093/eurheartj/ehw106.
    1. Coleman RL, Stevens RJ, Retnakaran R, Holman RR. Framingham, SCORE, and DECODE risk equations do not provide reliable cardiovascular risk estimates in type 2 diabetes. Diabetes Care. 2007;30(5):1292–1293. doi: 10.2337/dc06-1358.
    1. Berkelmans GFN, Gudbjörnsdottir S, Visseren FLJ, Wild SH, Franzen S, Chalmers J, Davis BR, Poulter NR, Spijkerman AM, Woodward M, et al. Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus. Eur Heart J. 2019;40(34):2899–2906. doi: 10.1093/eurheartj/ehy839.

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