Zepbound and Trulicity are two of the most widely prescribed injectable medications for managing type 2 diabetes and supporting weight loss. Both belong to the family of incretin-based therapies, but they work in different ways and produce noticeably different results for many patients. Zepbound, which contains tirzepatide, is a dual GIP and GLP-1 receptor agonist, while Trulicity (dulaglutide) targets only GLP-1 receptors.
The choice between Zepbound and Trulicity often comes down to how much blood sugar reduction or weight loss a patient needs, how well they tolerate side effects, cost considerations, and insurance coverage. Doctors frequently compare the two when patients aren’t reaching their A1C goals or want greater help with weight. Understanding the key differences helps people have more informed conversations with their healthcare providers.
In 2025, both medications remain popular, but Zepbound has pulled ahead in head-to-head studies and real-world use for weight loss and overall metabolic improvement. This guide breaks down the comparison in detail so you can see which option may be better suited for your individual health needs.
How Zepbound and Trulicity Work Differently
Zepbound (tirzepatide) is unique because it activates both GLP-1 and GIP receptors. GIP, another gut hormone, enhances insulin release and may improve fat metabolism. This dual action gives Zepbound a stronger effect on blood sugar control and appetite suppression compared to single-target drugs.
Trulicity (dulaglutide) is a pure GLP-1 receptor agonist. It primarily increases insulin secretion when blood sugar is high, slows gastric emptying, and reduces glucagon. While very effective for many, it lacks the additional GIP pathway that contributes to Zepbound’s greater potency.
The dual mechanism explains why Zepbound often produces larger A1C reductions and more substantial weight loss in clinical head-to-head studies. Both drugs are once-weekly injections, but their biological effects are distinctly different.
What’s Better Zepbound vs Trulicity: The Direct Answer
Zepbound is generally better than Trulicity for most patients who need maximum blood sugar control and weight loss. Head-to-head clinical trials (including SURPASS-2) showed Zepbound delivered greater A1C reductions (up to 2.4% vs 1.4–1.9% with Trulicity) and significantly more weight loss (average 12–17 kg vs 6–10 kg). Real-world data and patient reports in 2025 continue to show Zepbound outperforming Trulicity on both efficacy measures.
Trulicity may be better for patients who prioritize a longer track record, fewer gastrointestinal side effects, or lower cost with insurance coverage. Zepbound tends to cause more intense nausea and digestive issues early in treatment, while Trulicity is often better tolerated. The choice ultimately depends on your specific goals, tolerance, and insurance situation.
Step 1: Define Your Primary Treatment Goals
Talk with your doctor about your main priorities: maximum A1C reduction, greatest weight loss, fewer side effects, cost/insurance coverage, or a combination of these. If weight loss is the top goal, Zepbound usually has a clear advantage.
Review your current A1C, weight, and any previous medication experiences. Patients with higher starting A1C or more body weight often see the biggest differences between the two drugs.
Step 2: Compare Clinical Trial and Real-World Results
Look at head-to-head data: Zepbound consistently shows 0.5–1% greater A1C drops and roughly double the weight loss compared to Trulicity in the same studies. Real-world registries and patient surveys in 2025 confirm this gap persists outside controlled trials.
Consider tolerability: Trulicity users tend to report fewer severe gastrointestinal side effects. If you’re sensitive to nausea or vomiting, Trulicity may be easier to tolerate long-term.
Step 3: Evaluate Cost, Insurance, and Practical Factors
Check your insurance formulary. Trulicity is often covered more favorably or at a lower copay on many plans. Zepbound, being newer, may require prior authorization or have higher out-of-pocket costs. Use manufacturer savings cards for both to reduce expenses.
Think about convenience: both are weekly injections, but Zepbound’s higher doses sometimes produce stronger results with the same injection frequency. Discuss which option fits your lifestyle and budget best.
| Category | Zepbound (tirzepatide) | Trulicity (dulaglutide) | Winner for Most Patients |
|---|---|---|---|
| A1C Reduction (average) | 1.8–2.4% | 1.4–1.9% | Zepbound |
| Weight Loss (average) | 12–17 kg (26–37 lb) | 6–10 kg (13–22 lb) | Zepbound |
| Common GI Side Effects | More frequent/intense (nausea, diarrhea) | Less frequent/intense | Trulicity |
| Tolerability / Discontinuation | Higher early discontinuation rate | Lower discontinuation rate | Trulicity |
| Insurance Coverage (2025) | Often requires PA; variable copays | More consistent coverage; lower copays | Trulicity |
| Long-Term Data / Track Record | Newer (approved 2022) | Longer track record (approved 2014) | Trulicity |
This table compares Zepbound and Trulicity across the most important categories based on clinical trials, real-world evidence, and 2025 patient/insurance data.
Blood Sugar Control: Zepbound vs Trulicity
Zepbound consistently outperforms Trulicity in A1C reduction across multiple head-to-head studies. In the SURPASS-2 trial, patients on the highest Zepbound dose achieved an average A1C drop of 2.3% compared to 1.9% with the highest Trulicity dose. More Zepbound users reached A1C targets below 7% and even below 6.5%.
Real-world registries in 2025 show similar trends. Patients switching from Trulicity to Zepbound often report further A1C improvements. The dual mechanism gives Zepbound an edge in tackling both fasting and post-meal glucose levels.
For patients struggling to reach or maintain target A1C, Zepbound is usually the stronger choice. Trulicity still performs well, especially for those who need moderate control with fewer side effects.
Weight Loss Comparison: Zepbound vs Trulicity
Weight loss is where Zepbound pulls far ahead. In direct comparisons, Zepbound users lost roughly double the weight of Trulicity users over the same time frame. Average losses of 26–37 pounds with Zepbound versus 13–22 pounds with Trulicity are typical in head-to-head trials.
The additional GIP action in Zepbound appears to enhance fat metabolism and appetite suppression beyond what GLP-1 alone can achieve. Patients who prioritize maximum weight reduction almost always prefer Zepbound when tolerability allows.
Trulicity still delivers meaningful weight loss for many, especially those who cannot tolerate Zepbound’s stronger gastrointestinal effects. The difference is most noticeable in patients with higher starting body weight.
Side Effects and Tolerability Comparison
Gastrointestinal side effects are the most common with both drugs. Zepbound tends to cause more frequent and intense nausea, vomiting, diarrhea, and constipation, especially during dose escalation. Trulicity generally has a milder GI profile, making it easier for some patients to stay on treatment.
Injection-site reactions are rare and mild for both. Injection fatigue (feeling tired after the shot) is reported slightly more often with Zepbound due to its stronger metabolic effects. Most side effects for both drugs improve significantly after the first 8–12 weeks.
Discontinuation rates are higher with Zepbound in the early months because of GI intolerance. Patients who tolerate the initial phase usually stay on long-term with either medication.
Cost and Insurance Coverage in 2025
Zepbound is typically more expensive than Trulicity without insurance or manufacturer savings. List price for a 28-day supply of Zepbound ranges from $1,000–$1,300, while Trulicity often falls around $800–$1,000. Manufacturer savings cards can reduce out-of-pocket costs significantly for both.
Insurance coverage varies widely. Trulicity, being older, is more likely to be preferred on formularies and require less prior authorization. Zepbound often faces stricter step therapy or PA requirements. Check your specific plan and use savings programs to lower costs.
Both companies offer patient assistance programs for uninsured or underinsured individuals. Walmart, CVS, and other major pharmacies often have competitive cash prices with coupons.
Patient Experiences and Real-World Results
Many patients who switch from Trulicity to Zepbound report better blood sugar control and more weight loss, but some switch back because of increased nausea or vomiting. Those who tolerate Zepbound rarely go back to Trulicity due to superior efficacy.
Online communities show a split: people who prioritize maximum results tend to favor Zepbound, while those who want a gentler introduction and fewer side effects often stay with Trulicity. Individual tolerance plays a huge role in satisfaction.
Doctors frequently start patients on Trulicity for its longer track record and milder side effects, then switch to Zepbound if greater weight loss or A1C reduction is needed. Personalized choice leads to the best outcomes.
Summary
When comparing Zepbound vs Trulicity, Zepbound is generally better for patients who need the maximum possible blood sugar reduction and weight loss. Head-to-head trials and real-world data show Zepbound delivers greater A1C drops (up to 2.4% vs 1.9%) and roughly double the weight loss (26–37 lb vs 13–22 lb) compared to Trulicity. Its dual GIP/GLP-1 mechanism gives it a clear efficacy advantage.
Trulicity is better for patients who prioritize milder side effects, a longer track record, or easier insurance coverage. It tends to cause less intense nausea and digestive issues, making it easier to tolerate for some. The choice depends on your specific goals, tolerance, and insurance situation.
Both medications are effective and safe when used as prescribed. Work closely with your healthcare provider to decide which is the best fit for your needs. Regular monitoring ensures you get the most benefit with the least risk.
FAQ
Which is better for weight loss: Zepbound or Trulicity?
Zepbound is significantly better for weight loss. Clinical trials show average reductions of 26–37 pounds with Zepbound compared to 13–22 pounds with Trulicity over similar time frames. The dual mechanism in Zepbound produces stronger appetite suppression and fat loss.
Which has fewer side effects: Zepbound or Trulicity?
Trulicity generally has fewer and milder gastrointestinal side effects. Nausea, vomiting, and diarrhea are less frequent and less intense with Trulicity. Zepbound tends to cause stronger digestive issues, especially during dose increases.
Is Zepbound or Trulicity better for blood sugar control?
Zepbound is better for blood sugar control. Head-to-head studies show greater A1C reductions (up to 2.4% vs 1.9%) and more patients reaching target levels with Zepbound. The additional GIP action gives it an edge.
Which is cheaper: Zepbound or Trulicity?
Trulicity is usually cheaper, especially with insurance. It is older, more widely covered, and often requires less prior authorization. Zepbound tends to have higher out-of-pocket costs and stricter coverage rules. Manufacturer savings cards can reduce costs for both.
Can I switch from Trulicity to Zepbound?
Yes, many patients switch from Trulicity to Zepbound for better weight loss and blood sugar control. The switch is usually straightforward, but you may experience more gastrointestinal side effects initially. Your doctor will guide the transition and dose adjustment.
Dr. Hamza is a medical content reviewer with over 12+ years of experience in healthcare research and patient education. He specializes in evidence-based health information, medications, and chronic conditions. His reviews are grounded in trusted medical sources and current clinical guidelines to ensure accuracy, transparency, and reliability. Content reviewed by Dr. Hamza is intended for educational purposes and is not a substitute for professional medical advice.