Tirzepatide for Obesity
Treatment & Diabetes Prevention
A Summary of the 3-Year Clinical
Study
Published in NEJM, 2025
Background
• - Obesity increases the risk of type 2 diabetes.
• - Prediabetes affects 2/3 of people with
obesity, with a 70% lifetime risk of diabetes.
• - Weight loss improves insulin sensitivity and
beta-cell function.
• - Tirzepatide is a GIP/GLP-1 receptor agonist
with proven benefits in weight loss & glucose
control.
• - Study extends previous research to assess
long-term outcomes (3 years).
Study Design & Methods
• - Phase 3, double-blind, randomized, placebo-
controlled trial.
• - 2539 participants, 1032 with prediabetes.
• - Groups: Tirzepatide (5 mg, 10 mg, 15 mg) vs.
Placebo.
• - 176 weeks of treatment + 17 weeks off-
treatment.
• - Lifestyle intervention included diet &
exercise.
Weight Loss Outcomes
• - At 176 weeks, average weight loss:
• • 5 mg: -12.3%
• • 10 mg: -18.7%
• • 15 mg: -19.7%
• • Placebo: -1.3%
• - Over 85% of tirzepatide users lost ≥5%
weight vs. 29.5% placebo.
• - Higher doses led to greater, sustained weight
loss.
Diabetes Prevention
• - 1.3% of tirzepatide users developed diabetes
vs. 13.3% in placebo.
• - 92% of tirzepatide users reverted to
normoglycemia vs. 58.9% placebo.
• - After stopping treatment, diabetes rates
remained lower in tirzepatide group (2.4% vs.
13.7%).
• - Shows strong potential for long-term
diabetes prevention.
Safety & Side Effects
• - Most common side effects: mild to moderate
GI issues (nausea, diarrhea, constipation).
• - Serious adverse event rates similar to
placebo.
• - Slightly higher rates of gallbladder issues.
• - No major safety concerns over 3 years.
Post-Treatment Effects (Off-Drug
Period)
• - 7% weight regain after stopping treatment.
• - 15.5% of previous tirzepatide users reverted
to prediabetes.
• - 1.2% developed type 2 diabetes post-
treatment.
• - Suggests long-term treatment may be
needed for sustained benefits.
Study Strengths & Limitations
• **Strengths:**
• - Large sample size & long duration (3+ years).
• - Well-controlled, randomized trial.
• - Rigorous diabetes diagnosis criteria.
• **Limitations:**
• - High dropout rate (~35%).
• - Weight regain after stopping treatment.
• - Not directly compared with other weight-loss
Conclusion & Key Takeaways
• - Tirzepatide provides **sustained weight loss
& prevents diabetes** over 3 years.
• - **Long-term use may be necessary** to
maintain benefits.
• - **Significantly outperforms placebo** in
weight reduction & glucose control.
• - **Mild GI side effects** but no major safety
concerns.
• - **A promising treatment for obesity &
diabetes prevention!**
