SURMOUNT-1: How 2539 People Lost Up to 22.5% Weight in 72 Weeks — Complete Analysis of Revolutionary Study

When The New England Journal of Medicine published the SURMOUNT-1 results in 2022, the medical community was stunned. A 22.5% weight loss without surgical intervention? Previously, such numbers seemed unrealistic. Now they are confirmed by the highest standard of evidence-based medicine.

And here's what's interesting. This study didn't just show impressive results. It changed the very understanding of what can be achieved through medication in the fight against excess weight [8].

SURMOUNT-1 — what kind of study is this and why did it change everything?

SURMOUNT-1 is a phase 3 randomized controlled trial conducted by Eli Lilly and Company. Results were published on June 4, 2022, simultaneously in The New England Journal of Medicine and presented at the 82nd Scientific Sessions of the American Diabetes Association [5].

Why is this particular study considered groundbreaking? First, the scale. The study covered 2539 participants from 119 clinical centers in nine countries worldwide [13]. Second, duration. 72 weeks of observation — that's almost a year and a half, which allowed evaluation not only of rapid results but also their sustainability.

Tirzepatide became the first drug in its class to undergo global registration testing specifically for treating obesity in people without diabetes [23]. Previously, it was known as Mounjaro for treating type 2 diabetes, but SURMOUNT-1 opened a new chapter.

The study had a clear objective: to compare the efficacy and safety of tirzepatide with placebo in adults with obesity or overweight without diabetes mellitus. And the results exceeded the expectations of even the most optimistic researchers.

Methodology — how was the 4-arm study design built?

When talking about clinical trial quality, everything starts with methodology. SURMOUNT-1 was built according to the gold standard: multicenter, randomized, double-blind, placebo-controlled study [20].

What does "double-blind" mean? Neither participants nor researchers knew who received the real drug and who received placebo. This eliminates bias and ensures objectivity of results.

Participants were allocated in a 1:1:1:1 ratio to four groups [8]:

• Placebo (n=643)
• Tirzepatide 5 mg (n=630)
• Tirzepatide 10 mg (n=636)
• Tirzepatide 15 mg (n=630)

Analysis was conducted according to the intention-to-treat (ITT) principle, meaning all randomized participants were included in the analysis regardless of whether they completed the study [7]. This is a conservative approach that typically underestimates the real drug efficacy but ensures result reliability.

Additionally, a so-called treatment-regimen estimand was used — assessment of effects independent of treatment discontinuation in the ITT population [8]. This means that even if someone dropped out of the study, their data were considered in the final analysis.

There was also possibility of one-time dose de-escalation in case of intolerance. According to SURMOUNT-4 study data, 92.5% of participants were able to tolerate the maximum dose of 15 mg [3]. This is an important indicator that most people are capable of achieving optimal dosing.

Who participated in the study — profile of a typical participant

Inclusion criteria were carefully designed. The study included adults aged 18 and older with [8]:

• Body mass index (BMI) ≥30 kg/m² (obesity), OR
• BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) [22]

Critically important: people with type 2 diabetes were NOT included in this study [5]. This allowed evaluation of efficacy specifically for weight correction without the influence of diabetes. For diabetics, a separate study SURMOUNT-2 was later conducted.

Additional requirement — history of at least one failed weight loss attempt through diet [16]. This is important: participants had already tried to lose weight through traditional methods and failed to achieve success.

Interesting point: female enrollment was limited to 70% to ensure adequate male representation [16]. Without this limitation, there would have been significantly more women, as they more often seek help with weight correction issues.

The average participant profile looked like this [15]:

• Average age: 45.3 years
• Women: 67%
• Average weight: 105 kg
• Average BMI: 38.1 kg/m²

Also worth mentioning: 40.6% of participants (1032 people) had prediabetes at randomization [1]. This allowed evaluation not only of weight reduction but also impact on glycemic status and diabetes prevention.

Dosing protocol — 20-week titration to maximum dose

One of tirzepatide's key features is gradual dose escalation. This is not a drug that starts with the maximum dose from day one.

The titration scheme looked like this [2]:

The starting dose for all participants in the tirzepatide group was 2.5 mg. Then the dose was increased by 2.5 mg every 4 weeks until reaching the target maintenance dose [7]. The dose escalation period lasted 20 weeks.

Important nuance: unlike semaglutide, tirzepatide has three official maintenance doses — 5 mg, 10 mg, and 15 mg [2]. There's no requirement to reach the maximum dose. A client can stay on 5 mg or 10 mg long-term if this provides the desired result with good tolerability.

Injections were given subcutaneously once weekly [9]. Placebo group participants received corresponding placebo according to the same scheme to maintain study blinding.

The DOZA program uses original Mounjaro manufactured by Eli Lilly UK. Each KwikPen contains four doses, providing a month of use. The cost is fully justified by product quality and specialist support throughout the entire program.

Primary endpoints — the main numbers that changed medicine

SURMOUNT-1 had two coprimary endpoints [8]:

1. Mean percentage change in body weight from baseline to week 72
2. Percentage of participants achieving ≥5% weight reduction

Both endpoints had to be statistically significantly better compared to placebo. And tirzepatide achieved both.

Converting to kilograms: with an average initial weight of 105 kg, participants on the maximum dose lost an average of 24 kg (52 pounds) [23]. This isn't just "losing a couple of kilograms" — this is a fundamental change.

The second coprimary endpoint — percentage of participants with ≥5% weight loss [34]:

• Placebo: 28%
• Tirzepatide 5 mg: 85%
• Tirzepatide 10 mg: 89%
• Tirzepatide 15 mg: 89%

That means almost 9 out of 10 people on tirzepatide achieved clinically significant weight reduction. For comparison: in the placebo group, fewer than a third of participants achieved this result.

Regarding more ambitious goals — ≥20% weight loss [34]:

• Placebo: 1.3%
• Tirzepatide 5 mg: 32%
• Tirzepatide 10 mg: 55%
• Tirzepatide 15 mg: 63%

Secondary endpoints — what else improved besides weight?

Weight reduction is just the tip of the iceberg. SURMOUNT-1 showed significant improvements in a whole spectrum of cardiometabolic parameters [29].

Waist circumference — a critical marker of visceral obesity — significantly decreased in all tirzepatide groups compared to placebo [31]. Visceral fat is particularly dangerous as it's associated with increased risk of cardiovascular disease and diabetes.

Blood pressure also improved. Systolic and diastolic pressure decreased in tirzepatide groups, which is important for people with hypertension [29].

Lipid profile underwent positive changes:

• Triglyceride reduction
• Improved HDL/LDL ratio
• Total cholesterol reduction [33]

Fasting insulin levels decreased, indicating improved insulin sensitivity [29]. This is particularly important for type 2 diabetes prevention.

One of the most impressive results: at 72 weeks, 95.3% of participants with prediabetes at baseline who received tirzepatide returned to normal blood glucose levels. In the placebo group, this indicator was only 61.9% [29].

Quality of life also improved. Physical functioning scores on the SF-36 scale increased more in tirzepatide groups compared to placebo [35]. Participants felt more active and energetic.

Drug tolerability — what happens to the body and how to control it?

An honest analysis of any study is impossible without analyzing side effects. SURMOUNT-1 showed a typical safety profile for this drug class.

Overall incidence of adverse events [27]:

• Placebo: 72% of participants reported at least one adverse event
• Tirzepatide 5 mg: 78.9%
• Tirzepatide 10 mg: 81.4%
• Tirzepatide 15 mg: 81.8%

The most common adverse events were gastrointestinal and predominantly mild to moderate in severity, typically occurring during the dose escalation period [28]:

Important point: these symptoms were usually temporary and most commonly occurred precisely during gradual dose escalation [28]. After reaching the maintenance dose, the body adapted.

Treatment discontinuation rate due to adverse events [27]:

• Placebo: 2.6%
• Tirzepatide 5 mg: 4.3%
• Tirzepatide 10 mg: 7.1%
• Tirzepatide 15 mg: 6.2%

These numbers indicate overall good tolerability. The vast majority of participants were able to continue treatment. And those adverse events that occurred were manageable through dietary recommendations, symptomatic medications, or temporary skipping of one dose [10].

Why SURMOUNT-1 became the gold standard for comparison?

Before tirzepatide appeared, semaglutide (Wegovy/Ozempic) was considered the leader among weight correction medications. In the STEP-1 study, it showed 14.9% weight reduction over 68 weeks [35].

Tirzepatide exceeded this result by 50%. 22.5% versus 14.9% — this isn't just more, it's a qualitatively different level of efficacy.

What's the secret? Mechanism of action. Tirzepatide is a dual GLP-1 and GIP receptor agonist [9]. Semaglutide activates only GLP-1. The dual action provides enhanced effects on appetite, metabolism, and glucose control.

Sample size also matters. 2539 participants is a significant scale that ensures statistical power and result reliability [27]. Racial and ethnic diversity of participants increases the generalizability of conclusions.

Absence of serious "off-target" side effects is another argument in favor of tirzepatide [27]. The safety profile proved similar to other incretin-based drugs, without unexpected dangerous signals.

All this together made SURMOUNT-1 a benchmark study against which all subsequent weight correction medications are compared.

SURMOUNT series — from 2 to 5: what else did we learn?

SURMOUNT-1 became the first but not the only study in the program. Eli Lilly conducted an entire series of trials, each answering important clinical questions.

SURMOUNT-2 — study in people with obesity AND type 2 diabetes [36]. Results:

• Weight loss: 12.8% (10 mg) and 14.7% (15 mg) versus 3.2% on placebo
• HbA1c reduction: -2.07% (10 mg) and -2.08% (15 mg) versus -0.51%
• 87% of participants achieved HbA1c <7%
• 46-49% achieved HbA1c <5.7% (non-diabetic level)

SURMOUNT-3 — tirzepatide after intensive lifestyle modification program [16]. Participants first underwent a 12-week intensive dietary program, then received tirzepatide or placebo. This allowed evaluation of whether the drug enhances lifestyle intervention results.

SURMOUNT-4 — maintenance therapy study [10]. All participants first received tirzepatide for 36 weeks, then were randomized to continuation or placebo. The goal was to understand what happens to weight when the drug is discontinued and whether long-term therapy is needed.

SURMOUNT-OSA — two studies in people with obesity and obstructive sleep apnea [12]. One for those who could not or did not want to use CPAP therapy, another for those already using CPAP. Tirzepatide showed significant improvement in both weight and apnea parameters.

SURMOUNT-1 long-term follow-up — some participants with prediabetes were followed for 176 weeks (over 3 years) [14]. Results showed sustained weight reduction and significant reduction in risk of progression to type 2 diabetes.

This entire program forms a complete picture: tirzepatide is effective in different patient populations, with different comorbidities, and at different treatment stages.

How do study results translate to real practice?

Clinical trials are conducted under ideal conditions: careful participant selection, constant monitoring, motivated patients. What happens in real life?

DOZA experience shows that real-world results are close to clinical data. Our clients achieve 15-18% weight reduction in the first year of the program when following specialist recommendations.

Several factors influence real-world outcomes:

Individual response — each body reacts differently. Someone notices changes already on the starting dose of 2.5 mg, someone needs the maximum dose for optimal effect.

Compliance — regular application is critically important. Missed injections reduce efficacy.

Specialist support — proper dietary habit correction, timely dose titration, side effect management.

Initial BMI — people with higher BMI often lose more in absolute kilograms, although the percentage may be similar [15].

Plateau studies showed interesting dynamics: in SURMOUNT-1, the average BMI in the class III obesity category (highest) decreased from 46.1 kg/m² at baseline to 36.2 kg/m² at 72 weeks [15]. This is a transition from severe obesity to moderate — a significant health outcome.

It's important to understand: a weight loss program is a marathon, not a sprint. Results from clinical studies are achieved through a consistent, long-term approach. Learn more about the DOZA program and how it helps achieve sustainable results.

What remains open — an honest look at limitations

No study is perfect. Here are questions that SURMOUNT-1 didn't fully answer [27]:

Long-term safety — 72 weeks is a lot, but not the full picture. What happens after 5, 10, 20 years? Long-term observations are still ongoing [14], but final data is not yet available.

Cost and accessibility — the study did not take into account economic factors. For many people, the price of the medication can be a barrier. The DOZA program strives to make effective weight loss as accessible as possible, offering various dosage options for Mounjaro.

Weight maintenance after discontinuation — SURMOUNT-4 showed that when switching to placebo, part of the weight returns [10]. The question of optimal therapy duration and gradual program completion strategies remains relevant.

Specific populations — the study excluded people with type 1 diabetes, severe kidney and liver diseases, cancer history. Safety and efficacy in these groups requires separate study.

Comparison with other methods — direct comparison with bariatric surgery was not conducted. Although results are close, mechanisms and long-term consequences differ.

Despite these limitations, SURMOUNT-1 remains the most convincing evidence of obesity pharmacotherapy efficacy to date. The study changed the paradigm: weight loss is not only a matter of willpower, but a medical task that has a medical solution.

Where to buy

DOZA supplies the products mentioned in this article with an official cold chain and 24/7 specialist support:

• Buy Mounjaro in Ukraine — DOZA catalog with all 6 doses (2.5–15 mg) and official 24h cold-chain delivery. Current Mounjaro prices.

Frequently Asked Questions

What is SURMOUNT-1?

It is a phase 3 clinical trial that evaluated the efficacy and safety of tirzepatide for treating obesity in adults without diabetes. Results were published in the prestigious journal The New England Journal of Medicine in 2022.

What was the maximum weight loss in the SURMOUNT-1 study?

Participants on the maximum dose of 15 mg lost an average of 22.5% of their initial weight over 72 weeks, which is approximately 24 kg with an average initial weight of 105 kg.

How many people participated in SURMOUNT-1?

2539 adults from 119 clinical centers in nine countries worldwide. The average age of participants was 45 years, 67% were women.

What were the most common side effects?

The most common side effects were gastrointestinal: nausea (24-31%), diarrhea (15-23%), constipation (6-17%). They were predominantly mild to moderate and occurred during the dose escalation period.

How does SURMOUNT-1 differ from Ozempic studies?

Tirzepatide showed higher efficacy: 22.5% weight loss versus 14.9% for semaglutide (STEP-1 study). This is explained by tirzepatide's dual mechanism of action on GLP-1 and GIP receptors.

Where can I buy Mounjaro in Ukraine?

Original Mounjaro manufactured by Eli Lilly UK is available through the DOZA program. A specialist will select the optimal dosing and provide support throughout the program. See current prices and dosing in the catalog.

Is tirzepatide suitable for people with diabetes?

SURMOUNT-1 included only people without diabetes. For people with type 2 diabetes, a separate study SURMOUNT-2 was conducted, which also showed high efficacy for both weight reduction and glucose control.

If you're considering a weight loss program with Mounjaro, consultation with a DOZA specialist will help determine the optimal approach specifically for you. All this data points to one thing: effective weight loss is possible — and it starts with the first step.