FORO 2025 — Evidence Dashboard: Semaglutide vs Tirzepatide

Obesity-Related Complications Table 3

Anthropometric & CV Risk Factors Table 2A

Quality of Life & Function Table 2B

Anthropometric Parameters & CV Risk Factors

% Body Weight Reduction

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1, 68w) −14.9%

Semaglutide 2.4 mg (STEP UP, 72w) −17.5%

Semaglutide 7.2 mg (STEP UP, 72w) −20.7%

Tirzepatide 5 mg (SURMOUNT-1, 72w) −15.0%

Tirzepatide 10 mg −19.5%

Tirzepatide 15 mg −20.9%

Placebo −2.4 to −3.1%

STEP-1 · NEJM 2021 ↗ STEP UP · Lancet DE 2025 ↗ SURMOUNT-1 · NEJM 2022 ↗

Patients Achieving ≥10% Weight Loss

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1) 69.1%

Semaglutide 2.4 mg (STEP UP) 75.1%

Semaglutide 7.2 mg (STEP UP) 82.4%

Tirzepatide 5 mg 68.5%

Tirzepatide 10 mg 78.1%

Tirzepatide 15 mg 83.5%

Placebo 12–20.5%

STEP-1 · NEJM 2021 ↗ STEP UP · Lancet DE 2025 ↗ SURMOUNT-1 · NEJM 2022 ↗

Waist Circumference Reduction (cm)

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1) −13.5 cm

Semaglutide 7.2 mg (STEP UP) −17.5 cm

Tirzepatide 5 mg −14.0 cm

Tirzepatide 15 mg −18.5 cm

Placebo −4.0 to −5.9 cm

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

Change in Total Fat Mass

Semaglutide

−25.1%

Pooled fat volume reduction (STEP UP) vs −0.9% placebo. STEP-1: −8.36 kg vs −1.37 kg placebo

STEP-1 + STEP UP

Tirzepatide

−33.9%

Absolute fat mass reduction vs −8.2% with placebo. Improved fat/lean mass ratio at all doses

SURMOUNT-1

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

Blood Pressure Reduction (placebo-adjusted)

SYSTOLIC BP (mmHg)

Sema 2.4 mg (STEP-1)−5.1

Sema 7.2 mg (STEP UP)−9.9

Tirzepatide 5 mg−5.8

Tirzepatide 10 mg−7.0

DIASTOLIC BP (mmHg)

Sema 2.4 mg (STEP-1)−2.4

Sema 7.2 mg (STEP UP)−4.5

Tirzepatide 10 mg−4.5

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

Total Cholesterol (placebo-adjusted)

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1)−5.93%

Semaglutide 2.4 & 7.2 mg (STEP UP)−5%

Tirzepatide (SURMOUNT-1)−3.1%

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

LDL Cholesterol (placebo-adjusted)

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1)−6.55%

Semaglutide 2.4 & 7.2 mg (STEP UP)−7%

Tirzepatide (SURMOUNT-1)−4.2%

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

HDL Cholesterol (placebo-adjusted)

STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP UP)+6%

Semaglutide 7.2 mg (STEP UP)+8%

Tirzepatide (SURMOUNT-1)+8.8%

STEP UP ↗ SURMOUNT-1 ↗

Triglycerides (placebo-adjusted)

STEP-1 STEP UP SURMOUNT-1

Semaglutide 2.4 mg (STEP-1)−18.34%

Semaglutide 2.4 mg (STEP UP)−16%

Semaglutide 7.2 mg (STEP UP)−23%

Tirzepatide (SURMOUNT-1)−20.3%

STEP-1 ↗ STEP UP ↗ SURMOUNT-1 ↗

Quality of Life, Behavioural Regulation & Physical Function

SF-36 · Quality of Life

✓

Semaglutide Improvement

✓

Tirzepatide Improvement

IWQOL-Lite-CT · Quality of Life

✓

Semaglutide Improvement

✓

Tirzepatide Improvement

SF-36 · Physical Function

✓

Semaglutide Improvement

✓

Tirzepatide SF-36 v2 improved

IWQOL-Lite-CT · Physical Function

✓

Semaglutide Improvement

✓

Tirzepatide Improvement

Effects on Craving / Behavioural Regulation

Semaglutide

✓ Improvement

Improved control of eating demonstrated over 2 years of treatment (STEP 5 trial)

STEP 5 (Phase III)

Tirzepatide

— No studies

No dedicated studies evaluating craving or behavioural regulation available

STEP-1 (QoL) · NEJM 2021 ↗ STEP 5 (Craving) · Obesity 2023 ↗ SURMOUNT-1 QoL · DOM 2024 ↗

Effects on Obesity-Related Complications

🫀 Risk of MACE — SELECT Trial ▼

Semaglutide 2.4 mg Phase III

SELECT Trial — Primary Endpoint

1.00

0.90

0.80

0.70

0.60

0.50

−20%

HR = 0.80

95% CI 0.72–0.90

P < 0.001

3-point MACE composite:

CV death Non-fatal MI Non-fatal stroke

Semaglutide569 patients (6.5%)

Placebo701 patients (8.0%)

In patients with pre-existing ASCVD, regardless of diabetes status, after 40 months of treatment

Tirzepatide Under evaluation

⏳ Pending

Currently under evaluation in the SURMOUNT-MMO trial (Phase III), a major cardiovascular outcomes study. Results awaited.

SURMOUNT-MMO

Semaglutide 2.4 mg Phase III

SELECT Trial — CV Death

1.00

0.90

0.80

0.70

0.60

0.50

−15%

HR = 0.85

95% CI 0.71–1.01

P = 0.07 (NS)

First confirmatory secondary endpoint:

Death from cardiovascular causes

Semaglutide223 patients (2.5%)

Placebo262 patients (3.0%)

Did not reach nominal significance level for superiority (required P ≤ 0.023). CI crosses 1.0, suggesting a trend but not a statistically confirmed benefit.

Tirzepatide No data

—

No CV death endpoint data available. Awaiting SURMOUNT-MMO results.

Semaglutide 2.4 mg Phase III

SELECT Trial — Heart Failure Composite

1.00

0.90

0.80

0.70

0.60

0.50

−18%

HR = 0.82

95% CI 0.71–0.96

Endpoint:

Heart failure composite

Semaglutide300 patients (3.4%)

Placebo361 patients (4.1%)

SELECT trial additional endpoint.

Semaglutide 2.4 mg Phase III

SELECT Trial — Death from Any Cause

1.00

0.90

0.80

0.70

0.60

0.50

−19%

HR = 0.81

95% CI 0.71–0.93

Endpoint:

Death from any cause

Semaglutide375 patients (4.3%)

Placebo458 patients (5.2%)

SELECT trial additional endpoint.

SELECT · NEJM 2023 ↗ SURMOUNT-MMO · ClinicalTrials.gov ↗

💓 HFpEF ▼

Semaglutide Phase III

+7.8 pts

KCCQ-CSS score improvement vs placebo. Significant improvement in heart failure symptoms, functional status, and exercise capacity.

STEP-HFpEF

Tirzepatide Phase III

+9.8 pts

KCCQ-CSS score improvement vs placebo. 38% reduction in worsening HF events or CV death at 104 weeks.

SUMMIT

KCCQ-CSS Score Improvement (pts, placebo-adjusted)

Semaglutide+7.8

Tirzepatide+9.8

STEP-HFpEF · NEJM 2023 ↗ SUMMIT · NEJM 2025 ↗

🩸 Prediabetes ▼

Semaglutide Phase III

81%

Reversion to normoglycaemia vs 14% with placebo after 52 weeks

STEP 10

Tirzepatide Phase III

−93%

Reduction in the risk of developing type 2 diabetes after 176 weeks

SURMOUNT-4

STEP 10 · Lancet DE 2024 ↗ SURMOUNT-4 · NEJM 2024 ↗

💉 Type 2 Diabetes (HbA1c) ▼

HbA1c Reduction (%, placebo-adjusted)

Semaglutide 2.4 mg−1.2%

Tirzepatide 10 mg−1.6%

Tirzepatide 15 mg−1.6%

STEP 2 · Lancet 2021 ↗ SURMOUNT-2 · Lancet 2023 ↗

🧪 MASH (Steatohepatitis) ▼

Semaglutide Phase III

62.9%

MASH remission without worsening of fibrosis (vs 34.3% placebo). Fibrosis improvement without worsening of steatohepatitis: 36.8% vs 22.4% placebo.

Tirzepatide Phase II

Promising

Phase II trial showed promising results for MASH resolution and fibrosis improvement. Phase III data awaited.

Sema MASH Ph3 · NEJM 2025 ↗ SYNERGY-NASH Ph2 · NEJM 2024 ↗

😴 Obstructive Sleep Apnoea ▼

Semaglutide No studies

—

No dedicated studies available

Tirzepatide Phase III

AHI reduction (episodes/hour, placebo-adjusted)

Without PAP

−20.0

With PAP

−23.8

SURMOUNT-OSA

SURMOUNT-OSA · NEJM 2024 ↗

🦵 Knee Osteoarthritis ▼

Semaglutide Phase III

+14.2

WOMAC pain score improvement (points, placebo-adjusted). Significant reduction in knee pain and improved function.

STEP-KOA

Tirzepatide No studies

—

No dedicated studies available

STEP-KOA · NEJM 2024 ↗