Key result
Dipeptidyl peptidase-4 inhibitors were associated with a lower risk for major adverse cardiovascular events compared to sulfonylureas (aHR 0.84) in high-risk patients with type 2 diabetes.
Why the study?
Clinical trials evaluating DPP-4i cardiovascular safety rarely enroll patients with renal impairment, despite their increased risk for MACE.
Does dipeptidyl peptidase-IV inhibitors (DPP-4i) reduce major adverse cardiovascular events in patients with diabetes, comorbid with cardiovascular disease and/or renal impairment compared to sulfonylurea or metformin?
Cohort (n=113,296)
Does dipeptidyl peptidase-IV inhibitors (DPP-4i) reduce major adverse cardiovascular events in patients with diabetes, comorbid with cardiovascular disease and/or renal impairment compared to sulfonylurea or metformin?
Hazard Ratio: 0.84 (95% CI 0.74–0.93)
Absolute Event Rate: 91.25% vs 121.63%
In high-risk patients with diabetes and cardiovascular or renal disease, initiation of DPP-4i is associated with a lower risk of MACE compared to sulfonylureas and a similar risk compared to metformin.
DPP-4i may be cautiously preferred over sulfonylureas in high-risk renal patients; extends observational safety data but leaves open need for randomized confirmation.
Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). We investigated the risk of MACE associated with the use of DPP-4i among these high-risk patients. Using a new-user, retrospective, cohort design, we analyzed 2010-2015 IBM MarketScan Commercial Claims and Encounters for patients with diabetes, comorbid with cardiovascular disease and/or renal impairment. We compared time to first MACE for DPP-4i versus sulfonylurea and versus metformin. Of 113,296 individuals, 9146 (8.07%) were new DPP-4i users, 17,481 (15.43%) were new sulfonylurea users, and 88,596 (78.20%) were new metformin users. Exposure groups were not mutually exclusive. DPP-4i was associated with lower risk for MACE than sulfonylurea (aHR 0.84; 95% CI 0.74, 0.93) and similar risk for MACE to metformin (aHR 1.07; 95% CI [1.04, 1.16]). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. This association was most evident in the first year of therapy, suggesting that DPP-4i is a safer choice than sulfonylurea for diabetes treatment initiation in high-risk patients.
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Baksh et al. (2021) conducted a cohort in Type 2 diabetes with cardiovascular disease and/or renal impairment (n=113,296). Dipeptidyl peptidase-4 inhibitors (DPP-4i) vs. Sulfonylureas was evaluated on Major adverse cardiovascular events (MACE) (aHR 0.84, 95% CI 0.74-0.93). Dipeptidyl peptidase-4 inhibitors were associated with a lower risk for major adverse cardiovascular events compared to sulfonylureas (aHR 0.84) in high-risk patients with type 2 diabetes.
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