Introduction: Why Heart Health Matters in Type 2 Diabetes
People with type 2 diabetes (T2D) face a higher risk of heart attacks, strokes, and cardiovascular (CV) deaths. That’s why new diabetes drugs are tested in cardiovascular outcomes trials (CVOTs).
At the 2025 European Association for the Study of Diabetes (EASD) meeting, results from the SURPASS-CVOT trial were presented. This was the first head-to-head CV trial comparing two active drugs — tirzepatide (Mounjaro) and dulaglutide (Trulicity) — instead of comparing a drug to placebo.
SURPASS-CVOT at a Glance
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Participants: 13,165 adults with T2D and established cardiovascular disease.
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Design: Weekly tirzepatide (up to 15 mg) vs dulaglutide 1.5 mg.
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Follow-up: 4 years, across 640 sites in 30 countries.
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Goal: Compare rates of CV death, heart attack, or stroke.
Key Results: Tirzepatide Is Cardioprotective, But Not Superior
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Primary endpoint: Tirzepatide reduced major CV events by 8% compared to dulaglutide (HR 0.92). This showed noninferiority (not worse than dulaglutide) but not superiority.
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All-cause death: Lower with tirzepatide (8.6% vs 10.2%; HR 0.84).
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Blood sugar control: Greater HbA1c reduction (-1.7% vs -0.9%).
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Weight loss: Nearly double the reduction (-12.1% vs -5.0%).
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Kidney health: Significant benefit, particularly in patients with chronic kidney disease (CKD).
Side Effects: A Trade-Off for Potency
Tirzepatide was associated with more gastrointestinal side effects than dulaglutide:
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Nausea (25% vs 22%)
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Diarrhea (25% vs 19%)
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Decreased appetite (17% vs 10%)
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Constipation, vomiting, and indigestion also slightly higher
No increase in hypoglycemia or other serious adverse events was reported.
Comparison With Placebo (REWIND Study Insights)
Although SURPASS-CVOT did not include a placebo group, researchers compared tirzepatide’s results with placebo outcomes from the earlier REWIND trial (which studied dulaglutide).
Against placebo, tirzepatide showed:
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28% reduction in major CV events (HR 0.72).
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39% reduction in all-cause death (HR 0.61).
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30% reduction in CV death or heart failure events (HR 0.70).
This suggests tirzepatide has robust cardiovascular benefit, consistent with or stronger than GLP-1 receptor agonists.
Expert Opinions: Should Patients Switch?
Dr. Stephen Nicholls, lead investigator, noted:
“Tirzepatide is a good cardioprotective agent, but we need to personalize treatment decisions. For patients at higher kidney risk, tirzepatide may be the better choice.”
Dr. Hertzel Gerstein added:
“Tirzepatide is more potent but also has more side effects. If a patient is doing well on dulaglutide, there may be no need to switch. It comes down to balancing efficacy and tolerability.”
Takeaway for Patients and Clinicians
The SURPASS-CVOT trial confirms that tirzepatide is as heart-protective as dulaglutide, with added benefits for weight loss, blood sugar, and kidney outcomes. However:
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It is not superior to dulaglutide in cardiovascular protection.
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It may be preferable for patients needing more weight or kidney benefits.
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Side effects are more common and may limit use in some patients.
Tirzepatide vs. Dulaglutide: A Comparison
| Feature | Tirzepatide (Mounjaro®) | Dulaglutide (Trulicity®) |
|---|---|---|
| Drug Class | Dual GIP and GLP-1 receptor agonist | GLP-1 receptor agonist |
| FDA Approval | Type 2 diabetes (2022); obesity (Zepbound®, 2023) | Type 2 diabetes (2014) |
| Mechanism | Activates both GIP and GLP-1 receptors → stronger effects on insulin secretion, satiety, and weight loss | Activates GLP-1 receptors → improves insulin secretion, slows gastric emptying, reduces appetite |
| Administration | Weekly subcutaneous injection | Weekly subcutaneous injection |
| Dosage Range | 2.5 mg → up to 15 mg once weekly | 0.75 mg → up to 4.5 mg once weekly |
| Effect on A1C | Reduces A1C by ~2.0–2.3% | Reduces A1C by ~1.3–1.8% |
| Weight Loss | Average 10–15% body weight reduction in trials | Average 3–6% body weight reduction |
| Cardiovascular Outcomes | Cardiovascular outcome trial (SURPASS-CVOT) ongoing | Proven cardiovascular benefit (REWIND trial) |
| Side Effects | Nausea, vomiting, diarrhea, reduced appetite; similar to GLP-1s but slightly stronger | Nausea, vomiting, diarrhea, reduced appetite |
| Availability | Brand names: Mounjaro® (diabetes), Zepbound® (obesity) | Brand name: Trulicity® |
| Cost (U.S.) | Higher (newer drug, limited insurance coverage for obesity use) | Slightly lower, more widely covered by insurance |
| Best For | Patients needing both strong A1C reduction and significant weight loss | Patients prioritizing glucose control with proven CV benefit |
Frequently Asked Questions (FAQ)
1. Is tirzepatide better than dulaglutide for heart health?
No, tirzepatide was found to be equally protective but not superior to dulaglutide in preventing major heart events.
2. Does tirzepatide help with weight loss more than dulaglutide?
Yes. In SURPASS-CVOT, patients on tirzepatide lost about 12% of body weight, compared to 5% with dulaglutide.
3. Is tirzepatide good for kidney health?
Yes. Tirzepatide reduced the risk of kidney disease progression, especially in people who already had CKD.
4. What are the main side effects of tirzepatide?
The most common are nausea, diarrhea, decreased appetite, constipation, and vomiting.
5. Should patients switch from dulaglutide to tirzepatide?
Not automatically. Dulaglutide remains effective and well-tolerated. Tirzepatide may be better for those needing more weight or kidney benefit but comes with more GI side effects.
✅ Bottom line: Tirzepatide is a powerful diabetes drug with cardiovascular, kidney, and weight benefits. But when it comes to heart protection, it’s not superior to dulaglutide. The choice between the two should be individualized based on patient needs and tolerance.
