Dipeptidyl peptidase-4 inhibitor use was associated with a lower 3-year risk of MACE compared to sulfonylureas in a TECOS trial-matched cohort (17.0% vs 19.5%; RR 0.87; 95% CI 0.87-0.88; p<0.001).
Cohort (n=416,162)
Does DPP-4i reduce 4-point MACE compared to sulfonylurea in people with type 2 diabetes?
Real-world data from the UK CPRD suggests DPP-4i treatment is associated with a lower risk of MACE compared to sulfonylureas in patients with type 2 diabetes, with a more pronounced effect in those with pre-existing cardiovascular disease.
Relative Risk: 0.87 (95% CI 0.87–0.88)
Absolute Event Rate: 17% vs 19.5%
p-value: p=<0.001
Introduction and Objective: The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS, n=14,671) showed that sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), does not increase the risk of major cardiovascular events in people with type 2 diabetes. Whether DPP-4i effects differ in a real-world general population is uncertain. This study examined the association of DPP-4i compared to sulfonylurea (SU) with cardiovascular outcomes using UK Clinical Practice Research Datalink (CPRD) real-world data. Methods: Among 527,381 CPRD individuals with type 2 diabetes receiving DPP-4i or SU, we created two groups: a trial-matched group that met the TECOS inclusion criteria (aged ≥50 years with HbA1c between 48-64 mmol/mol and pre-existing cardiovascular disease) and an unmatched group that did not meet the TECOS inclusion criteria. The primary outcome was 4-point MACE 3 years after treatment initiation. Longitudinal targeted maximum likelihood estimation was used to evaluate the association between DPP-4i vs SU treatment and MACE risk, adjusting for baseline and time-varying covariates. Results: We included 11,987 individuals with complete data in the trial-matched group and 404,175 in the unmatched group (51% DPP-4i users in both groups). The trial-matched group was older (72(SD 10) vs 62(14) years) with lower HbA1c (57.3(4.6) vs 75(21) mmol/mol). At 3 years, the cumulative risk of MACE in the trial-matched group was lower for DPP-4i than SU users (17.0 vs 19.5%) with a risk ratio (RR) of 0.87 (95% CI 0.87-0.88, p0.001). Whilst MACE risk was lower for DPP-4i users vs SU (5.5 vs 5.7%) in the unmatched group (RR 0.96 (0.96-0.97), p0.001), this was not clinically significant. Conclusion: DDP-4i treatment was associated with lower MACE risk than SU treatment in people with type 2 diabetes in the TECOS trial-matched group, but the magnitude of this effect was smaller in the unmatched group. Disclosure G. Martine-Edith: None. J.J. Thomas: None. S. Gharibzadeh: None. S. Misra: Other - Speaker honorarium for a single presentation at a conferences; Ended; A. Menarini Diagnostics, Lilly Diabetes. Advisory Panel; Ended; Insulet Corporation. Other - Speaker honoararium for a single presentation at a conferences; Ended; Sanofi. K. Khunti: None. J.K. Mader: Research Support; Current; A. Menarini Diagnostics. Advisory Panel; Current; Abbott Diabetes. Speaker's Bureau; Current; Abbott Diabetes. Advisory Panel; Current; Becton, Dickinson and Company. Speaker's Bureau; Current; Becton, Dickinson and Company. Advisory Panel; Current; Insulet Corporation, Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi. Advisory Panel; Current; Novo Nordisk A/S. Speaker's Bureau; Current; Novo Nordisk A/S. Advisory Panel; Current; Roche Diagnostics. Speaker's Bureau; Current; Roche Diagnostics. Advisory Panel; Current; Medtronic, Tandem Diabetes Care, Inc., Omnipod. Stock/Shareholder; Current; decide Clinical Software GmbH. Advisory Panel; Current; Dexcom, Inc. Speaker's Bureau; Current; Dexcom, Inc., Sinocare, Buzud. Advisory Panel; Current; Biomea Fusion, Pharmasens. Stock/Shareholder; Current; elyte Diagnostics. Other - CMO (unpaid); Current; elyte Diagnostics. Speaker's Bureau; Current; A. Menarini Diagnostics. Board Member; Current; OMNIA by AI APS. Advisory Panel; Current; Triple Jump. P. Choudhary: Advisory Panel; Current; Medtronic. Speaker's Bureau; Current; Medtronic. Research Support; Current; Medtronic. Consultant; Current; Medtronic. Speaker's Bureau; Current; Abbott. Advisory Panel; Current; Abbott. Research Support; Current; Abbott. Speaker's Bureau; Current; Dexcom, Inc. Advisory Panel; Current; Dexcom, Inc. Research Support; Current; Dexcom, Inc. Consultant; Current; Dexcom, Inc. Speaker's Bureau; Current; Insulet Corporation. Advisory Panel; Current; Insulet Corporation. Research Support; Current; Insulet Corporation. Consultant; Current; Insulet Corporation. Speaker's Bureau; Current; Sanofi. Consultant; Current; Sanofi. Speaker's Bureau; Current; Lilly. Advisory Panel; Current; Lilly. Consultant; Current; Lilly. Advisory Panel; Current; Ypsomed AG. Advisory Panel; Ended; Embecta. Speaker's Bureau; Current; Roche Diabetes Care. Research Support; Current; Roche Diabetes Care. Consultant; Current; Roche Diabetes Care. Advisory Panel; Current; Vertex Pharmaceuticals Incorporated. Consultant; Current; Glooko, Inc., Cambridge Mechatronics Ltd, vTv Therapeutics.
MARTINE-EDITH et al. (Fri,) conducted a cohort in Type 2 diabetes (n=416,162). Dipeptidyl peptidase-4 inhibitors (DPP-4i) vs. Sulfonylurea (SU) was evaluated on 4-point MACE 3 years after treatment initiation (RR 0.87, 95% CI 0.87-0.88, p=<0.001). Dipeptidyl peptidase-4 inhibitor use was associated with a lower 3-year risk of MACE compared to sulfonylureas in a TECOS trial-matched cohort (17.0% vs 19.5%; RR 0.87; 95% CI 0.87-0.88; p<0.001).
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