Ozempic Vs Mounjaro -SURMOUNT 5

Written By Dr. Ryan Oughtred

Last week, Lilly released results of it’s head to head trial of tirzepatide—sold as Mounjaro (for type 2 diabetes) and ZepBound (for obesity) — against the likes of Semaglutide — commercialized as Wegovy (for obesity) and Ozempic (for type 2 diabetes).

The SURMOUNT 5 trial demonstrated that:

  • “Zepbound® (tirzepatide) provided a 47% greater relative weight loss compared to Wegovy® (semaglutide).

  • On average, Zepbound led to a superior weight loss of 20.2% compared to 13.7% with Wegovy

  • At 72 weeks, Zepbound beat Wegovy on both the primary endpoint and all five key secondary endpoints in this trial of adults living with obesity or overweight with at least one weight-related medical problem and without diabetes.”

So is Mounjaro better than Ozempic for weight loss?

A high quality trial that was paid for by Lilly says yes. Not everyone needs >20% weight loss, and the costs of these medications might differ depending on where you live and your insurance coverage. Both medications are comparable and are part of the “2nd generation” of game changing medications for ABCD/ Obesity.

Want to learn more about the SURMOUNT trials? Read on….

A Summary of the SURMOUNT Trials of Tirzepatide (Mounjaro®/ZepBound®) for ABCD/ Obesity/ Weight:

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist — this means that, unlike semaglutide (Ozempic/ Wegovy), it is a molecule that is designed to interact with multiple receptors in the body, not just the GLP-1 receptor.

It has been investigated for weight management across multiple phase 3 clinical trials known collectively as the SURMOUNT program. These trials examined tirzepatide’s efficacy and safety in diverse populations of adults with obesity or overweight, both with and without type 2 diabetes, and in various clinical contexts, including after lifestyle interventions and in direct comparison with another anti-obesity medication. Throughout these studies, tirzepatide (marketed as Mounjaro in type 2 diabetes and ZepBound in obesity) demonstrated substantial, sustained weight reductions and favorable cardiometabolic improvements, with tolerable and generally mild-to-moderate gastrointestinal side effects.

SURMOUNT-1 (NCT04184622)

Rationale and Population: The efficacy and safety of tirzepatide in people with obesity (BMI ≥30) or overweight (BMI ≥27) and at least one weight-related complication, but without diabetes, were previously unknown. This first SURMOUNT trial aimed to establish whether tirzepatide could produce significant weight reduction compared with placebo over 72 weeks.

Design:

  • Participants: 2,539 adults, mean baseline weight 104.8 kg, mean BMI 38.0.

  • Intervention: Once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period.

Results (Week 72):

  • Mean % Weight Change:

    • Tirzepatide 5 mg: -15.0% (95% CI, -15.9 to -14.2)

    • Tirzepatide 10 mg: -19.5% (95% CI, -20.4 to -18.5)

    • Tirzepatide 15 mg: -20.9% (95% CI, -21.8 to -19.9)

    • Placebo: -3.1% (95% CI, -4.3 to -1.9)

  • ≥5% Weight Reduction:

    • Tirzepatide 5 mg: 85%

    • Tirzepatide 10 mg: 89%

    • Tirzepatide 15 mg: 91%

    • Placebo: 35%

  • ≥20% Weight Reduction:

    • Tirzepatide 10 mg: 50%

    • Tirzepatide 15 mg: 57%

    • Placebo: 3%

Safety: Gastrointestinal events were most common, generally mild to moderate. Treatment discontinuation due to adverse events occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants in the 5 mg, 10 mg, 15 mg tirzepatide, and placebo groups, respectively.

SURMOUNT-2 (NCT04657003)

Rationale and Population: Managing weight in adults with both obesity or overweight and type 2 diabetes is more challenging. SURMOUNT-2 aimed to determine the effect of tirzepatide on body weight in this population over 72 weeks.

Design:

  • Participants: 938 adults with a mean BMI of 36.1 and mean HbA1c of 8.02%, aged ≥18, with type 2 diabetes.

  • Intervention: Once-weekly subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks, with lifestyle interventions.

Results (Week 72):

  • Mean % Weight Change:

    • Tirzepatide 10 mg: -12.8% (SE 0.6)

    • Tirzepatide 15 mg: -14.7% (SE 0.5)

    • Placebo: -3.2% (SE 0.5)

  • ≥5% Weight Reduction: 79–83% with tirzepatide vs. 32% with placebo.

Safety: Gastrointestinal side effects were the most common, mild to moderate, and few led to discontinuation (<5%).

SURMOUNT-3

Rationale and Population: The effect of tirzepatide on weight loss after a successful intensive lifestyle intervention was unknown. SURMOUNT-3 evaluated whether adding tirzepatide after a 12-week diet-based lead-in period (during which participants achieved ≥5% weight loss) could produce further reductions at 72 weeks.

Design:

  • Participants: 579 adults with obesity or overweight and at least one weight-related complication (excluding diabetes), who achieved ≥5% weight loss in a 12-week intensive lifestyle intervention.

  • Intervention: Once-weekly tirzepatide (10 or 15 mg) vs. placebo for 72 weeks.

Results (Week 72 from Randomization):

  • Additional Mean % Weight Change (beyond the initial ≥5% already lost):

    • Tirzepatide: -18.4% (SE 0.7)

    • Placebo: +2.5% (SE 1.0)

    • Difference: -20.8 percentage points (P < 0.001)

  • ≥5% Additional Weight Reduction:

    • Tirzepatide: 87.5%

    • Placebo: 16.5% (P < 0.001)

Safety: Most common adverse events were gastrointestinal, mild to moderate in severity.

SURMOUNT-4

Rationale and Population: The long-term maintenance of weight loss after initially successful treatment with tirzepatide was unknown. SURMOUNT-4 assessed the effect of continuing vs. discontinuing tirzepatide after significant weight loss had already been achieved.

Design:

  • Participants: 783 adults with obesity or overweight and at least one weight-related complication, excluding diabetes. All received once-weekly tirzepatide (10 or 15 mg) for a 36-week open-label lead-in, achieving a mean weight reduction of 20.9%. At week 36, 670 participants were randomized to continue tirzepatide or switch to placebo for 52 weeks, totaling 88 weeks.

Results:

  • From Randomization (Week 36) to Week 88:

    • Continued Tirzepatide: -5.5% additional mean weight loss

    • Switched to Placebo: +14.0% weight regain

    • Difference: -19.4% (P < 0.001)

  • Maintaining ≥80% of the Weight Loss Achieved During Lead-In:

    • Tirzepatide: 89.5%

    • Placebo: 16.6% (P < 0.001)

  • Total Mean Weight Change From Baseline to Week 88:

    • Tirzepatide: -25.3%

    • Placebo: -9.9%

Safety: Gastrointestinal events were the most common, mild to moderate, and occurred more frequently with continued tirzepatide.

SURMOUNT-5 (NCT05822830)

Rationale and Population: With an increasing number of anti-obesity medications, direct comparisons are needed. SURMOUNT-5 compared ZepBound (tirzepatide) head-to-head against Wegovy® (semaglutide), both given once weekly over 72 weeks to adults with obesity or overweight (with at least one weight-related medical problem), excluding diabetes, to determine which offered greater weight reduction.

Design:

  • Participants: 751 adults from the U.S. and Puerto Rico, BMI ≥30 or ≥27 with a weight-related complication.

  • Intervention: Maximum tolerated dose of ZepBound (10 mg or 15 mg tirzepatide) vs. Wegovy (1.7 mg or 2.4 mg semaglutide) for 72 weeks.

Results (Week 72):

  • Mean % Weight Reduction:

    • ZepBound: -20.2%

    • Wegovy: -13.7%

  • ≥25% Weight Loss:

    • ZepBound: 31.6%

    • Wegovy: 16.1%

ZepBound achieved a superior weight loss of 20.2% vs. 13.7% with Wegovy, representing a 47% greater relative weight reduction.

Safety: The safety profiles of both drugs were similar, with gastrointestinal events (nausea, diarrhea, vomiting) as the most common, mild-to-moderate side effects.

Conclusion
Across the SURMOUNT trials, tirzepatide —commercialized as Mounjaro (for type 2 diabetes) and ZepBound (for obesity) - delivered substantial weight reductions in individuals without diabetes, those with type 2 diabetes, after lifestyle-induced weight loss, and compared directly with another obesity medication such as Semaglutide, commercialized as Wegovy (for obesity) and Ozempic (for type 2 diabetes).

References:

  • Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216.

  • Garvey WT, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26. PMID: 37385275.

  • Wadden, T.A., Chao, A.M., Machineni, S. et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med 29, 2909–2918 (2023). https://doi.org/10.1038/s41591-023-02597-w

  • Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945

  • SURMOUNT 5 - Eli Lilly Press Release Dec 4 - 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head

Dr. Ryan Oughtred
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