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Comparative Study
. 2024 Oct 12:2024:6142211.
doi: 10.1155/2024/6142211. eCollection 2024.

Empagliflozin Use Is Associated With Lower Risk of All-Cause Mortality, Hospitalization for Heart Failure, and End-Stage Renal Disease Compared to DPP-4i in Nordic Type 2 Diabetes Patients: Results From the EMPRISE (Empagliflozin Comparative Effectiveness and Safety) Study

Gisle Langslet  1 , Thomas Nyström  2 , Dorte Vistisen  3   4 , Bendix Carstensen  3 , Emilie Toresson Grip  5   6 , Paula Casajust  7 , Giorgi Tskhvarashvili  8 , Fabian Hoti  9 , Riho Klement  10 , Kristina Karlsdotter  11 , Mikko Tuovinen  12 , Anne Pernille Ofstad  13   14 , Maria Lajer  15 , Christina Shay  16 , Lisette Koeneman  17 , Soulmaz Fazeli Farsani  18 , Leo Niskanen  19   20 , Sigrun Halvorsen  21   22
Affiliations
Comparative Study

Empagliflozin Use Is Associated With Lower Risk of All-Cause Mortality, Hospitalization for Heart Failure, and End-Stage Renal Disease Compared to DPP-4i in Nordic Type 2 Diabetes Patients: Results From the EMPRISE (Empagliflozin Comparative Effectiveness and Safety) Study

Gisle Langslet et al. J Diabetes Res. .

Abstract

Objective: To evaluate the effectiveness of empagliflozin in reducing all-cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end-stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Methods: This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor) during 2014-2018 who were compared to those initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta-analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random-effects models were calculated. Results: A total of 43,695 pairs of PS-matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40-0.64) compared to DPP-4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46-0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37-0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15-0.77) compared to DPP-4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP-4i. Results were generally consistent for subgroups (with/without pre-existing CV disease or congestive heart failure) and in sensitivity analyses. Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

Keywords: cardiovascular diseases; comparative effectiveness; dipeptidyl peptidase-4 inhibitors; empagliflozin; end-stage renal disease; heart failure; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes mellitus.

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Conflict of interest statement

Dorte Vistisen has received research grants from Bayer A/S, Sanofi, Novo Nordisk A/S, and Boehringer Ingelheim. She holds shares in Novo Nordisk A/S. Bendix Carstensen declares no conflicts of interest. Sigrun Halvorsen has received speaker fees from Sanofi, Novartis, Boehringer Ingelheim, Bayer, Pfizer, and Bristol-Myers Squibb. Gisle Langslet has received consulting/lecture fees from Sanofi and Boehringer Ingelheim. Thomas Nyström has received unrestricted grants from AstraZeneca and Novo Nordisk and has been a national adviser of Abbot, Amgen, Novo Nordisk, Sanofi-Aventis, Eli Lilly, MSD, and Boehringer Ingelheim. Leo Niskanen has received speaker honoraria from Amgen, Boehringer Ingelheim, Novo Nordisk, Sanofi, MSD, and Astra Zeneca; research support from Novo Nordisk to the hospital; and has participated in the scientific advisory boards of Amgen, Boehringer Ingelheim, AstraZeneca, MSD, and Novo Nordisk. Paula Casajust is an employee of TFS Health Science. Giorgi Tskhvarashvili, Fabian Hoti, and Riho Klement are/were employees of IQVIA contracted by Boehringer Ingelheim to conduct the meta-analyses, interpret the results, review, and revise the manuscript. Christina Shay, Soulmaz Fazeli Farsani, Kristina Karlsdotter, Mikko Tuovinen, Anne Pernille Ofstad, and Maria Lajer were employees of Boehringer Ingelheim at the time of manuscript development. Lisette Koeneman is an employee of Eli Lilly and Company and owns stock in Eli Lilly and Company. Emilie Toresson Grip is an employee of Quantify Research that was contracted to conduct the country-specific studies in Finland, Norway, and Sweden.

Figures

Figure 1
Figure 1
Overview of the study periods. AT = as-treated; DPP-4i = dipeptidyl peptidase-4 inhibitor; MA = marketing authorization; PS = propensity score; SGLT2i = sodium-glucose cotransporter-2 inhibitor. 1In analyses investigating effectiveness outcomes, the occurrence of the outcome in question was observed until the end of the follow-up (e.g., while investigating hospitalization for heart failure, the follow-up did not end at the occurrence of a stroke).
Figure 2
Figure 2
Attrition flowchart for four countries from inclusion to propensity score matched pairs. DPP-4i = dipeptidyl peptidase-4 inhibitor; ESRD = end-stage renal disease; PS = propensity score; SGLT2i = sodium-glucose cotransporter-2 inhibitor; T2D = type 2 diabetes.
Figure 3
Figure 3
Results of the meta-analysis for (a) all-cause mortality (ACM), (b) hospitalization for heart failure (HHF), (c) myocardial infarction (MI), and (d) stroke. Analysis details: As-treated (AT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals.
Figure 4
Figure 4
Results of the meta-analysis for (a) cardiovascular mortality (CVM) and (b) end-stage renal disease (ESRD). Analysis details: As-treated (AT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals.
Figure 5
Figure 5
Results of the meta-analysis for (a) all-cause mortality (ACM) and (b) hospitalization for heart failure (HHF) among patients with and without pre-existing congestive heart failure (CHF). Analysis details: As-treated (AT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals. The time window for CHF is ever before the index date.
Figure 6
Figure 6
Results of the meta-analysis for (a) myocardial infarction (MI) and (b) stroke among patients with and without pre-existing congestive heart failure (CHF). Analysis details: As-treated (AT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals. The time window for CHF is ever before the index date.
Figure 7
Figure 7
Results of the meta-analysis for (a) all-cause mortality (ACM) and (b) hospitalization for heart failure (HHF) among patients with and without pre-existing cardiovascular (CV) disease. Analysis details: As-treated (AT). Country-level results with insufficient number of events for analysis in either of the study groups are omitted from the analysis. Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals. The time window for CV disease is ever before the index date.
Figure 8
Figure 8
Results of the meta-analysis for (a) myocardial infarction (MI) and (b) stroke among patients with and without pre-existing cardiovascular (CV) disease. Analysis details: As-treated (AT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, a total number of events and incidence rates are presented as intervals. The time window for CV disease is ever before the index date.
Figure 9
Figure 9
Results of ITT sensitivity analysis for (a) all-cause mortality (ACM), (b) hospitalization for heart failure (HHF), (c) myocardial infarction (MI), and (d) stroke. Analysis details: Intention-to-treat (ITT). Numbers < 5 are not shown due to data protection, but they are included in meta-analysis. If values < 5 exist, total number of events and incidence rates are presented as intervals.
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