TY - JOUR
T1 - Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors
T2 - an analysis from the CVD-REAL 2 multinational cohort study
AU - Kohsaka, Shun
AU - Lam, Carolyn S.P.
AU - Kim, Dae Jung
AU - Cavender, Matthew A.
AU - Norhammar, Anna
AU - Jørgensen, Marit E.
AU - Birkeland, Kåre I.
AU - Holl, Reinhard W.
AU - Franch-Nadal, Josep
AU - Tangri, Navdeep
AU - Shaw, Jonathan E.
AU - Ilomäki, Jenni
AU - Karasik, Avraham
AU - Goh, Su Yen
AU - Chiang, Chern En
AU - Thuresson, Marcus
AU - Chen, Hungta
AU - Wittbrodt, Eric
AU - Bodegård, Johan
AU - Surmont, Filip
AU - Fenici, Peter
AU - Kosiborod, Mikhail
AU - Wilding, John P.
AU - Khunti, Kamlesh
AU - Birkeland, Kåre
AU - Jørgensen, Marit Eika
AU - Holl, Reinhard W.
AU - Lam, Carolyn SP
AU - Gulseth, Hanne Løvdal
AU - Carstensen, Bendix
AU - Bollow, Esther
AU - García Rodríguez, Luis Alberto
AU - Shaw, Jonathan
AU - Arnold, Suzanne
AU - Blak, Betina T.
AU - Wittbrodt, Eric T.
AU - Saathoff, Matthias
AU - Noguchi, Yusuke
AU - Tan, Donna
AU - Williams, Maro
AU - Lee, Hye Won
AU - Greenbloom, Maya
AU - Kaidanovich-Beilin, Oksana
AU - Yeo, Khung Keong
AU - Bee, Yong Mong
AU - Khoo, Joan
AU - Koong, Agnes
AU - Lau, Yee How
AU - Gao, Fei
AU - Tan, Wee Boon
AU - Kadir, Hanis Abdul
AU - Ha, Kyoung Hwa
AU - Lee, Jinhee
AU - Chodick, Gabriel
AU - Melzer-Cohen, Cheli
AU - Whitlock, Reid
AU - Cea-Soriano, Lucia
AU - Cantero, Oscar Fernándex
AU - Menzin, Jordan A.
AU - Guthrie, Matthew
AU - Ilomaki, Jennie
AU - Magliano, Dianna
N1 - Funding Information:
The funder of the study was involved in study design, data collection, data analysis, and data interpretation. Employees of the funder were authors on this paper, and were therefore involved in writing of the report. Editorial support in styling, formatting, and submitting this report was provided by a medical writer funded by the sponsor. The corresponding author and senior author had full access to all the data in the study, vouch for the accuracy and completeness of data reported, and had final responsibility for the decision to submit for publication.
Funding Information:
SK has received research grants and consulting fees from Bayer, research grants from Daiichi Sankyo, and speaker fees from Bristol-Myers Squibb and AstraZeneca. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the advisory board, steering committee, or executive committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, Cytokinetics, WebMD Global, Radcliffe Group, and Corpus; and serves as cofounder and non-executive director of eKo.ai. DJK has received research grant support from LG Life Sciences, Chong Kun Dang, and AstraZeneca; has been a consultant for AstraZeneca, Novo Nordisk, and Sanofi; and has received speaker fees from Novo Nordisk, Takeda, Handok, CJ Healthcare, Chong Kun Dang, MSD, Hanmi, and AstraZeneca. MAC has received research grants and personal fees from Amgen, personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Novo Nordisk, and Merck; and research grants from Bristol Myers Squibb, CSL Behring, and Novartis. AN has received honoraria for lectures and advisory board meetings from AstraZeneca, Novo Nordisk, MSD, Boehringer Ingelheim, and Lilly. MEJ has received research grants from AstraZeneca, Amgen, Boehringer Ingelheim, and Sanofi Aventis; is a shareholder of Novo Nordisk; and has received speaker fees from Novo Nordisk. KIB has received research grants and non-financial support (for keeping and maintaining the database and statistical analyses) from AstraZeneca related to the present study; and research grants from Boehringer Ingelheim, MSD, Sanofi, Novo Nordisk, and Eli Lilly. RWH has received research grants to his institution from AstraZeneca, including support for the present study. NT has received consulting fees from Boehringer Ingelheim, Eli Lilly, Otsuka, and AstraZeneca; research grants from AstraZeneca, including support for the present study; research grants from Janssen and Tricida; and consulting fees and stock options from Tricida, PulseData, and Mesentech. JES has received honoraria for advisory board participation and lectures from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mylan Pharmaceuticals, and Novo Nordisk. JI has consulted for AstraZeneca Australia. AK has received consulting fees from AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. S-YG has received research grants to her institution from AstraZeneca, Medtronic, and Sanofi; and honoraria for advisory board participation for Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Medtronic, and Sanofi. C-EC has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. MT is an employee of Statisticon, for which AstraZeneca is a client. HC, EW, FS, and PF are AstraZeneca employees and hold stock options in the company. JB is an AstraZeneca employee. MK has received research grants from AstraZeneca and Boehringer Ingelheim; and has served as a consultant for Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Glytec, Novo Nordisk, Janssen, Merck (Diabetes), Novartis, Sanofi, and Vifor Pharma.
Funding Information:
This study was funded by AstraZeneca. This analysis was overseen by the CVD-REAL 2 academic scientific committee and the CVD-REAL 2 Investigators and Study Group, including members from AstraZeneca. The members of the CVD-REAL 2 Investigators and Study Group are listed in the appendix. The authors acknowledge Kevin Kennedy (St Luke's Mid America Heart Institute, Kansas City, MO, USA) for his independent validation of the data. Editorial support for styling, formatting, and submission of the report was provided by Róisín O'Connor (inScience Communications, Springer Healthcare, London, UK), funded by AstraZeneca.
PY - 2020/7
Y1 - 2020/7
N2 - Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p<0·0001), all-cause death (0·59, 0·52–0·67; p<0·0001), and the composite of hospitalisation for heart failure or all-cause death (0·64, 0·57–0·72; p<0·0001). Risks of myocardial infarction (HR 0·88, 0·80–0·98; p=0·020) and stroke (0·85 0·77–0·93; p=0·0004) were significantly but modestly lower with SGLT2 inhibitors versus DPP-4 inhibitors. Interpretation: In this large, international, observational study, initiation of SGLT2 inhibitors versus DPP-4 inhibitors was associated with lower risks of heart failure, death, myocardial infarction, and stroke, providing further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes. Funding: AstraZeneca.
AB - Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p<0·0001), all-cause death (0·59, 0·52–0·67; p<0·0001), and the composite of hospitalisation for heart failure or all-cause death (0·64, 0·57–0·72; p<0·0001). Risks of myocardial infarction (HR 0·88, 0·80–0·98; p=0·020) and stroke (0·85 0·77–0·93; p=0·0004) were significantly but modestly lower with SGLT2 inhibitors versus DPP-4 inhibitors. Interpretation: In this large, international, observational study, initiation of SGLT2 inhibitors versus DPP-4 inhibitors was associated with lower risks of heart failure, death, myocardial infarction, and stroke, providing further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes. Funding: AstraZeneca.
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U2 - 10.1016/S2213-8587(20)30130-3
DO - 10.1016/S2213-8587(20)30130-3
M3 - Article
C2 - 32559476
AN - SCOPUS:85086397300
VL - 8
SP - 606
EP - 615
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
SN - 2213-8587
IS - 7
ER -