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Observational Study
. 2023 Jun 25;44(24):2216-2230.
doi: 10.1093/eurheartj/ehad273.

Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study

Edouard L Fu  1 , Elisabetta Patorno  1 , Brendan M Everett  2   3 , Muthiah Vaduganathan  2 , Scott D Solomon  2 , Raisa Levin  1 , Sebastian Schneeweiss  1 , Rishi J Desai  1
Affiliations
Observational Study

Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study

Edouard L Fu et al. Eur Heart J. .

Abstract

Aims: The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction.

Methods and results: Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding.

Conclusion: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.

Keywords: Cardiovascular diseases; Cohort studies; Heart failure; Sodium–glucose cotransporter 2 inhibitors; Type 2 diabetes mellitus.

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Conflict of interest statement

Conflict of interest E.P. is investigator of an investigator-initiated grant to the Brigham and Women’s Hospital from Boehringer Ingelheim, not directly related to the topic of the submitted work. B.M.E reports consulting fees from Gilead, Johnson & Johnson, Provention Bio, Eli Lilly and Company, Ipsen, Circulation Journal, Up to Date, and the NIDDK unrelated to the current work. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, speaker engagements with Novartis, and Roche Diagnostics and participates in clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. S.D.S. has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Cardiac Dimensions, Celladon, CellProThera, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and Us2.ai; has consulted for Abbott, Action, Akros, Alnylam, American Regent, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, and Sarepta and has stock options in Dinaqor. S.S. is participating in investigator-initiated grants to the Brigham and Women’s Hospital from Boehringer Ingelheim unrelated to the topic of this study; he is a consultant to Aetion, Inc., a software manufacturer of which he owns equity; his interests were declared, reviewed, and approved by the Brigham and Women’s Hospital in accordance with their institutional compliance policies. R.J.D. reports serving as Principal Investigator on research grants to Brigham and Women’s Hospital from Vertex, Novartis, and Bayer. No other potential conflicts of interest relevant to this article were reported.

Figures

Structured Graphical Abstract
Structured Graphical Abstract
This study investigated the effectiveness of SGLT2i vs. sitagliptin in patients with heart failure and type 2 diabetes in routine clinical practice. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary outcome and its individual components all-cause mortality, hospitalization for heart failure, and urgent visit requiring intravenous diuretics, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction. CI, confidence interval; HR, hazard ratio; SGLT2i, sodium–glucose cotransporter 2 inhibitors.
Figure 1
Figure 1
Weighted cumulative incidence for (A) the primary composite outcome of all-cause mortality or worsening heart failure, (B) all-cause mortality, (C) heart failure hospitalization, (D) treatment with intravenous diuretics in outpatient setting, and (E) worsening heart failure under 365-day intention-to-treat follow-up, stratified by sodium–glucose cotransporter 2 inhibitors or sitagliptin initiation.
Figure 1
Figure 1
Weighted cumulative incidence for (A) the primary composite outcome of all-cause mortality or worsening heart failure, (B) all-cause mortality, (C) heart failure hospitalization, (D) treatment with intravenous diuretics in outpatient setting, and (E) worsening heart failure under 365-day intention-to-treat follow-up, stratified by sodium–glucose cotransporter 2 inhibitors or sitagliptin initiation.
Figure 1
Figure 1
Weighted cumulative incidence for (A) the primary composite outcome of all-cause mortality or worsening heart failure, (B) all-cause mortality, (C) heart failure hospitalization, (D) treatment with intravenous diuretics in outpatient setting, and (E) worsening heart failure under 365-day intention-to-treat follow-up, stratified by sodium–glucose cotransporter 2 inhibitors or sitagliptin initiation.
Figure 2
Figure 2
Adjusted hazard ratios for the subgroup analyses for the primary composite outcome of all-cause mortality or worsening heart failure under 365-day intention-to-treat follow-up.
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