Articles Vol. 67 No. VTT

NARRATIVE REVIEW OF REPRESENTATIVE TRIALS ON INCRETIN-BASED THERAPIES (GLP-1 RECEPTOR AGONISTS, DPP-4 INHIBITORS) FOR WEIGHT MANAGEMENT AND TYPE 2 DIABETES CONTROL

Ngo Vo Truong Huy1,2, Phan Thanh Tai3,4
1 Vo Truong Toan University
2 Trường Đại Học Võ Trường Toản
3 Vo Truong Toan University Hospital
4 Bệnh Viện Đại Học Võ Trường Toản
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Keywords
GLP-1 receptor agonist; DPP-4 inhibitor; type 2 diabetes; weight management; cardiovascular outcomes.
Abstract

Objective: To synthesize evidence from cardiovascular outcome trials (CVOTs) and representative weight-loss trials on the efficacy and safety of incretin-based therapies GLP-1 receptor agonists (GLP-1RA) and DPP-4 inhibitors (DPP-4i) for weight and glycemic control in type 2 diabetes (T2D).

Methods: We conducted a narrative review of key CVOTs of GLP-1RA (LEADER, SUSTAIN-6, REWIND, SELECT, STEP-1) and DPP-4i (TECOS, SAVOR-TIMI 53, EXAMINE, CARMELINA). Additional cardiovascular outcome trials of GLP-1 receptor agonists were considered to illustrate heterogeneity among individual agents, although not all of these studies are presented in detail in this review. The 2025 ADA Standards of Care were used as the main framework; dual GIP/GLP-1 receptor agonists were mentioned as an emerging option but not discussed in depth.

Results: GLP-1RA lower HbA1c by approximately 1% and induce clinically meaningful weight loss (up to ~15% with semaglutide 2.4 mg in STEP-1), while reducing major adverse cardiovascular events with some agents (liraglutide, semaglutide, dulaglutide) and improving selected microvascular and renal outcomes. However, other CVOTs show that cardiovascular benefit is not uniform across all GLP-1RA. DPP-4i are weight-neutral, provide modest HbA1c reduction (~0.5–0.7%), and are generally cardiovascularly safe, except for saxagliptin, which increases the risk of hospitalization for heart failure.

Conclusion: In patients with T2D and overweight/obesity or established atherosclerotic cardiovascular disease, GLP-1RA from landmark trials are preferred over DPP-4i because of superior weight and cardiovascular benefits. DPP-4i are suitable when GLP-1RA are contraindicated or not tolerated. Treatment should be individualized according to the 2025 ADA recommendations, avoiding concomitant use of GLP-1RA and DPP-4i. This review focuses on representative trials and is not intended to comprehensively cover the entire incretin-based therapy literature.

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