Tirzepatide Clinical Trials: SURMOUNT Results and What They Mean

The SURMOUNT Trials: Tirzepatide for Weight Loss

The SURMOUNT trial program evaluated tirzepatide for chronic weight management, leading to the FDA approval of Zepbound on November 8, 2023. Tirzepatide is notable as the first dual GIP/GLP-1 receptor agonist approved for weight loss.

SURMOUNT-1: Adults Without Diabetes

Published in the New England Journal of Medicine in 2022, SURMOUNT-1 enrolled 2,539 adults with obesity or overweight (with at least one weight-related comorbidity) but without type 2 diabetes.

**Key results over 72 weeks, by dose:**

| Measure | 5 mg | 10 mg | 15 mg | Placebo |

|---------|------|-------|-------|---------|

| Average weight loss | **16.0%** | **21.4%** | **22.5%** | 3.1% |

| Achieved 5% or more loss | 85% | 89% | 91% | 35% |

| Achieved 20% or more loss | 16.5% | 35% | 39.7% | 1.5% |

At the highest dose (15 mg), nearly 4 in 10 participants lost 20% or more of their body weight -- a level of weight loss previously achievable only with bariatric surgery.

*Source: Jastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." NEJM 2022;387:205-216.*

SURMOUNT-2: Adults with Type 2 Diabetes

SURMOUNT-2 evaluated tirzepatide in adults who had both obesity/overweight and type 2 diabetes.

**Key results over 72 weeks:**

As with semaglutide, weight loss in people with type 2 diabetes was somewhat lower than in those without diabetes, though still clinically significant.

*Source: Garvey WT, et al. "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)." The Lancet 2023;402:613-626.*

Why Tirzepatide May Produce Greater Weight Loss

Tirzepatide targets two hormone receptors rather than one. While semaglutide activates only the GLP-1 receptor, tirzepatide also activates the GIP (glucose-dependent insulinotropic polypeptide) receptor. Research published in JCI Insight describes tirzepatide as an "imbalanced and biased dual GIP and GLP-1 receptor agonist," meaning it has particularly strong activity at the GIP receptor.

GIP receptors are found in fat tissue and in appetite-regulating areas of the brain. The dual mechanism is believed to explain the additional weight loss seen compared to GLP-1-only medications.

*Source: Willard FS, et al. "Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist." JCI Insight 2020;5(17):e140532.*

Side Effects in SURMOUNT Trials

The most common side effects in SURMOUNT-1 were gastrointestinal:

These effects were most common during the dose-escalation phase and generally decreased with continued use. About 4-7% of participants discontinued treatment due to side effects.

What This Means for Patients

The SURMOUNT data positions tirzepatide as the most effective injectable weight loss medication currently available in terms of average weight reduction. The 15 mg dose produced over 22% average weight loss, which approaches the results seen with some bariatric surgical procedures.

However, the optimal medication for any individual depends on their specific health profile, insurance coverage, tolerance of side effects, and other factors that should be discussed with a healthcare provider.

*All GLP-1 medications require a prescription from a licensed healthcare provider. This article is for educational purposes only and does not constitute medical advice.*