Semaglutide 2 mg Tied to Lower MACE Risk Than Tirzepatide Switch

Adults with type 2 diabetes (T2D) taking semaglutide injection 1 mg (Ozempic; Novo Nordisk) who escalated to the 2 mg dose had a modestly lower risk of major adverse cardiovascular events (MACE) than those who switched to tirzepatide (Mounjaro; Eli Lilly and Company). The finding comes from a Novo Nordisk–funded real-world analysis presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan, Italy.¹

The retrospective claims study cannot establish cause and effect, but it speaks to a decision pharmacists regularly help navigate: whether to intensify a patient's current glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) or switch agents.¹

Inside COMPETE SWITCH CV

The COMPETE SWITCH study used Komodo Health's Healthcare Map, a large US claims database with linked laboratory results, spanning January 2018 to September 2025. Among 636,525 adults with T2D receiving semaglutide 1 mg, 29.2% escalated to 2 mg and 3.6% switched to tirzepatide within 365 days. By 720 days, those figures were 36.9% and 5.7%.¹

The cardiovascular analysis used an intention-to-treat approach and included 185,705 adults who escalated to semaglutide 2 mg and 23,104 who switched to tirzepatide. MACE was defined as all-cause death, myocardial infarction, or stroke. The adjusted hazard ratio (HR) was 1.06 (95% CI, 1.04-1.08; P = .005), which Novo Nordisk characterized as a 6% lower MACE risk with semaglutide escalation. A subset of patients with more than 1 hemoglobin A1c (A1C) and/or weight measurement at baseline showed a consistent result (adjusted HR, 1.07; 95% CI, 1.01-1.13). Safety outcomes were not assessed, and the full data remain unpublished.¹

Important Caveats

Dosing was not equivalent between groups. Patients who switched started tirzepatide at 2.5 mg or 5 mg, and approximately 31% reached a dose of 10 mg or higher during follow-up. The comparison therefore largely pitted full-dose semaglutide against tirzepatide below its maximum dose.¹

Novo Nordisk acknowledged that real-world analyses may reflect residual unmeasured confounding. It also noted that retrospective claims data may exclude patients with intermittent coverage or underserved populations. Patients who switch agents may also differ from those who escalate in ways a claims database cannot fully capture.¹

How This Fits With Randomized Evidence

The 2 mg dose itself is supported by SUSTAIN FORTE (NCT03989232), a 40-week trial of 961 adults with T2D on metformin with or without a sulfonylurea. Semaglutide 2 mg lowered A1C by 2.2 percentage points vs 1.9 with 1 mg (trial product estimand). It produced 6.9 kg vs 6.0 kg of weight loss, with gastrointestinal disorders reported in 34% and 31% of participants, respectively.²

Randomized cardiovascular data for tirzepatide come from SURPASS-CVOT, which compared tirzepatide with dulaglutide in 13,165 patients with T2D and atherosclerotic cardiovascular disease. Tirzepatide was noninferior to dulaglutide for a composite of cardiovascular death, myocardial infarction, or stroke (HR, 0.92; 95.3% CI, 0.83-1.01) but did not meet superiority. That trial's primary end point counted cardiovascular death, whereas COMPETE SWITCH CV counted all-cause death, so the outcomes are not directly comparable.³

Takeaways for Pharmacists

For patients tolerating semaglutide 1 mg but not yet at goal, the findings add an observational data point in favor of in-class escalation. They do not show that switching to tirzepatide causes harm. Pharmacists supporting a switch should counsel patients that tirzepatide is restarted at a lower dose and titrated. Gastrointestinal adverse events were also more common with tirzepatide than with dulaglutide in SURPASS-CVOT.^1,3

REFERENCES

1. Novo's Ozempic (semaglutide) 2 mg associated with lower risk of major adverse cardiovascular events (death, heart attack, and stroke) in adults with type 2 diabetes compared to switching to Mounjaro (tirzepatide), in real-world analysis. News release. Novo Nordisk. September 29, 2026. Accessed September 29, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=917053

2. Frías JP, Auerbach P, Bajaj HS, et al. Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. Lancet Diabetes Endocrinol. 2021;9(9):563-574. doi:10.1016/S2213-8587(21)00174-1

3. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-2420. doi:10.1056/NEJMoa2505928