Key result
SGLT2i and GLP-1RA as add-on therapy were associated with a lower risk of MACE compared with DPP-4i (HR 0.66, 95% CI 0.50-0.85 for SGLT2i; HR 0.64, 95% CI 0.43-0.97 for GLP-1RA).
Why the study?
To evaluate the effect of SGLT2i and GLP-1RA compared with DPP-4i as add-on therapy on cardiovascular morbidity and mortality in patients with type 2 diabetes.
Do SGLT2 inhibitors or GLP-1 receptor agonists reduce major adverse cardiovascular events compared to DPP-4 inhibitors as add-on therapy in patients with type 2 diabetes?
Cohort (n=7,523)
Yes
Do SGLT2 inhibitors or GLP-1 receptor agonists reduce major adverse cardiovascular events compared to DPP-4 inhibitors as add-on therapy in patients with type 2 diabetes?
Hazard Ratio: 0.66 (95% CI 0.5–0.85)
p-value: p=0.002
Real-world data confirms that SGLT2 inhibitors and GLP-1 receptor agonists reduce cardiovascular morbidity and mortality compared to DPP-4 inhibitors in patients with type 2 diabetes.
May inform SGLT2i preference over DPP-4i in T2D; extends observational data but leaves randomized confirmation open.
OBJECTIVE: To evaluate the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy on cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes (T2D). DESIGN AND SETTING: A nationwide cohort study using three linked healthcare databases from Slovenia (outpatient prescription claims data, hospitalisation claims data and death registry data). PARTICIPANTS: Patients with T2D with newly introduced DPP-4i (n=3817), GLP-1RA (n=855) or SGLT2i (n=2851) add-on therapy between June 2014 and June 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a major adverse CV event (MACE), while the secondary outcomes were CV death and heart failure (HF). The effects of the antidiabetic medicine group on the risk of each outcome were estimated with Cox proportional hazards regression. Intention-to-treat and on-treatment approaches were used. RESULTS: In the intention-to-treat analysis, SGLT2i as add-on therapy, when compared with DPP-4i, was associated with lower risk of MACE (HR=0.66; 95% CI 0.50 to 0.85; p=0.002) and CV death (HR=0.46; 95% CI 0.30 to 0.73; p=0.001). On-treatment analysis revealed lower HF risk in patients initiating SGLT2i (HR=0.54; 95% CI 0.30 to 0.99; p=0.047). In the intention-to-treat analysis, GLP-1RA add-on therapy was associated with a lower MACE risk when compared with DPP-4i (HR=0.64; 95% CI 0.43 to 0.97; p=0.034), but it had a non-significant effect on CV death (HR=0.62; 95% CI 0.34 to 1.14; p=0.128) and HF (HR=1.39; 95% CI 0.88 to 2.21; p=0.157). The results of on-treatment analyses were in agreement with the results of intention-to-treat analyses. CONCLUSIONS: SGLT2i and GLP-1RA improved CV morbidity and mortality in patients with T2D when compared with DPP-4i as an add-on therapy. The results of this study may serve as a basis for the selection of an optimal add-on antidiabetic medicine to reduce CV morbidity and mortality in patients with T2D in clinical practice. TRIAL REGISTRATION NUMBER: EUPAS32558.
No takes yet. Share an insight, caveat, or question.
Žerovnik et al. (2021) conducted a cohort in type 2 diabetes (n=7,523). SGLT2i or GLP-1RA vs. DPP-4i was evaluated on major adverse CV event (MACE) (HR 0.66, 95% CI 0.50 to 0.85, p=0.002). SGLT2i and GLP-1RA as add-on therapy were associated with a lower risk of MACE compared with DPP-4i (HR 0.66, 95% CI 0.50-0.85 for SGLT2i; HR 0.64, 95% CI 0.43-0.97 for GLP-1RA).