Comparative Effectiveness of Second-Line Antidiabetic Medications on the Risk of Major Adverse Cardiovascular Events: A Real-World Study in China

Author(s)

Yuqing Fan, BS1, Nan Peng, MSc2, Linfeng Jiang, BS1, Shuo Zhang, BS1, Mengyao Xue, BS1, Chen Mu, BS1, Dongning Yao, Phd3.
1Nanjing Medical University, Nanjing, Jiangsu, China, 2china pharmaceutical university, Beijing, China, 3Nanjing Medical University, Nanjing, China.
OBJECTIVES: To evaluate the comparative effectiveness of second-line antidiabetic medications (ADMs) on the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM).
METHODS: This retrospective cohort study utilized electronic medical records from a large healthcare platform in Eastern China. Adult patients with T2DM who initiated a second-line ADM after prior metformin monotherapy or no ADM between January 2018 and October 2024 were included. MACE was defined as a composite of stroke, myocardial infarction, and all-cause mortality. Survival models were used to estimate the risk of MACE. Both intention-to-treat (ITT) and per-protocol (PP; reflecting maintained use of the same ADM throughout follow-up) analyses were performed.
RESULTS: The final cohort included 119,810 initiators of GLP-1 receptor agonists (n=17,416), SGLT-2 inhibitors (n=19,863), DPP-4 inhibitors (n=6,880), insulin (n=41,349), sulfonylureas (n=21,549), α-glucosidase inhibitors (n=8,214), thiazolidinediones (n=1,029), and meglitinides (n=3,510). In the ITT analysis, compared with insulin, SGLT-2 inhibitors (HR 0.878, 95% CI [0.834-0.924], p<0.001), DPP-4 inhibitors (HR 0.826, 95% CI [0.770-0.886], p<0.001), and GLP-1 receptor agonists (HR 0.848, 95% CI [0.800-0.900], p<0.001) were associated with a reduced risk of MACE. Conversely, sulfonylureas (HR 1.093, 95% CI [1.045-1.144], p<0.001) and α-glucosidase inhibitors (HR 1.121, 95% CI [1.064-1.181], p<0.001) were associated with increased risk. Compared with DPP-4 inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists showed no significant differences in MACE risk. The PP analysis yielded similar results, with SGLT-2 inhibitors (HR 0.753, 95% CI [0.652-0.869], p<0.001), DPP-4 inhibitors (HR 0.654, 95% CI [0.520-0.823], p<0.001), and GLP-1 receptor agonists (HR 0.663, 95% CI [0.562-0.783], p<0.001) showing significantly lower risks compared with insulin.
CONCLUSIONS: SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists were associated with reduced risk of MACE compared to insulin, while sulfonylureas and α-glucosidase inhibitors were linked to increased cardiovascular risk.

Conference/Value in Health Info

2025-11, ISPOR Europe 2025, Glasgow, Scotland

Value in Health, Volume 28, Issue S2

Code

PT42

Topic

Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems

Topic Subcategory

Health & Insurance Records Systems

Disease

Cardiovascular Disorders (including MI, Stroke, Circulatory), Diabetes/Endocrine/Metabolic Disorders (including obesity), No Additional Disease & Conditions/Specialized Treatment Areas

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