In people with type 2 diabetes and established atherosclerotic cardiovascular disease, once-weekly tirzepatide has now been tested head-to-head against dulaglutide in the large SURPASS-CVOT outcomes trial. Dulaglutide already carries proven cardiovascular benefit, so this comparison provides an important benchmark for a newer, more potent incretin-based therapy.
SURPASS-CVOT enrolled 13,165 adults with type 2 diabetes, established cardiovascular disease and HbA1c 7.0–10.5%. They were randomised 1:1 to weekly tirzepatide (titrated to 15 mg) or dulaglutide 1.5 mg, on top of contemporary background therapy. Participants were followed for major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) as the primary endpoints.
Tirzepatide met the prespecified criterion for noninferiority to dulaglutide for 3-point MACE, confirming cardiovascular safety against an active cardioprotective comparator. Over a median 4.0 years, the primary composite of cardiovascular death, myocardial infarction or stroke occurred in 12.2% with tirzepatide and 13.1% with dulaglutide (HR 0.92, 95.3% CI 0.83–1.01; P=0.003 for non‑inferiority, P=0.09 for superiority). Component endpoints tended to favour tirzepatide (CV death HR 0.89; MI HR 0.86; stroke HR 0.91), but confidence intervals crossed 1.0, precluding a claim of superiority for MACE. A broader composite including coronary revascularisation was lower with tirzepatide (16.5% vs 18.5%; HR 0.88, 95% CI 0.81–0.96). All‑cause mortality was reduced (8.6% vs 10.2%; HR 0.84, 95% CI 0.75–0.94), driven by fewer non‑cardiovascular deaths (HR 0.75, 95% CI 0.63–0.91); these prespecified secondary findings are exploratory and hypothesis‑generating.
Beyond cardiovascular events, tirzepatide delivered substantially greater reductions in HbA1c- 1.66 vs −0.88 percentage points (between‑group −0.78) and body weight- 11.6% vs −4.8% (difference −6.8 percentage points) than dulaglutide, aligning with its dual GIP/GLP-1 receptor agonist profile. Emerging data also suggest a slower decline in renal function with tirzepatide in higher-risk subgroups
(eGFR −5.72 vs −8.90 ml/min/1.73 m²; difference 3.17 ml/min/1.73 m²), with modest additional reductions in systolic blood pressure and triglycerides, raising the possibility of additional kidney protection alongside cardiovascular safety.
Prespecified analyses indicate that tirzepatide is noninferior to dulaglutide for composite heart-failure outcomes, with some signals favouring tirzepatide when broader composite endpoints (including all-cause mortality) are considered, though these require cautious interpretation. Gastrointestinal adverse events remain more frequent with tirzepatide (42.5% vs 35.9%), consistent with more potent incretin activity, and will be a key practical consideration in routine care.
For clinicians managing high-risk type 2 diabetes, SURPASS-CVOT supports tirzepatide as a cardiovascular safe alternative to dulaglutide, with superior glycaemic and weight effects and potential renal advantages. Against the backdrop of established GLP-1–based cardio protection, treatment choice will likely hinge on individual priorities: weight loss and metabolic potency versus gastrointestinal tolerability, cost, and familiarity with existing GLP-1 receptor agonists.
1. Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, Lincoff AM, McGuire DK, Miller D, Nauck MA, Nishiyama H, Nissen SE, Sattar N, Weerakkody G, Wiese RJ, Zinman B, Zoungas S, Basile J, Davies MJ, Giorgino F, Kellerer M, Ji L, Varkonyi T, Menon V, Broder JC, Herschtal A, D’Alessio D; SURPASS-CVOT Investigators. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025 Dec 18;393(24):2409-2420. doi: 10.1056/NEJMoa2505928. PMID: 41406444.
2. Lam CSP, Rodriguez A, Aminian A, Ferrannini E, Heerspink HJL, Jastreboff AM, Laffin LJ, Pandey A, Ray KK, Ridker PM, Sanyal AJ, Yki-Jarvinen H, Mason D, Strzelecki M, Bartee AK, Cui C, Hurt K, Linetzky B, Bunck MC, Nissen SE. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial. Obesity (Silver Spring). 2025 Sep;33(9):1645-1656. doi: 10.1002/oby.24332. Epub 2025 Jun 22. PMID: 40545827.
