Int J Obes (Lond)Weight LossCohortDecember 8, 2025

A real-world study of tirzepatide for weight loss in adults without diabetes mellitus.

Angelopoulos N, Androulakis I, Rizoulis A, Boniakos A, Fousteris E, Mentzelopoulou V, Petkova V, Paparodis R, Zianni D, Florakis D, Korakovouni A, Mouslech Z, Livadas S, Tzoulis P

View on PubMed DOI: 10.1038/s41366-025-01986-0

Key Finding

Adults with obesity lost an average of 8.2 kg (7.3% of their body weight) in just 12 weeks on low-dose tirzepatide, with nearly half achieving clinically meaningful 5%+ weight loss.

What This Study Found

Think of tirzepatide as a dual-action appetite control system - it's like having two different locks on your hunger door instead of just one. This study followed 115 adults with obesity (but no diabetes) who started with a gentle 2.5mg weekly dose for a month, then stepped up to 5mg for the remaining two months - like gradually turning up the volume on your body's satiety signals. The results were impressive for such a short timeframe and low dose: people lost an average of 18 pounds, which is like losing a large watermelon's worth of weight. Beyond the scale victories, their bodies became metabolically healthier too - blood sugar levels improved even though they weren't diabetic, and their cholesterol profiles got better. It's like the medication was fine-tuning multiple health dials at once, not just the weight dial.

Statistics Decoded

7.3% average weight loss means if you weighed 220 pounds, you'd lose about 16 pounds on average. The 46.1% achieving ≥5% weight loss means nearly half the people hit what doctors consider clinically meaningful weight loss (think 11+ pounds for a 220-pound person). HbA1c dropping from 5.6% to 5.4% shows blood sugar control improved even in non-diabetics. Only 7.8% experienced nausea (about 9 people out of 115), and 10.4% stopped treatment (12 people) - mostly those who'd tried similar medications before and likely knew they couldn't tolerate them.

Why This Matters

This shows that even low-dose, short-term tirzepatide can deliver meaningful weight loss in real-world patients, not just perfect clinical trial conditions - giving doctors confidence to prescribe lower starting doses that patients might tolerate better while still seeing results.

Original Abstract

Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown substantial weight-loss efficacy in clinical trials, though typically at higher doses and longer treatment durations. Evidence on the short-term real-world effectiveness of low-dose tirzepatide in adults with obesity without diabetes is limited. In this prospective multicentre observational study, 115 adults with obesity but without diabetes were treated with tirzepatide 2.5 mg weekly for 4 weeks, titrated to 5 mg for a total of 12 weeks. Anthropometric and biochemical parameters were assessed at baseline and week 12. Mean body weight decreased by 8.2 ± 4.9 kg (-7.3% ±4.4%), with a BMI reduction of 2.8 ± 1.7 kg/m²; 46.1% achieved ≥5% weight loss. HbA1c decreased from 5.6 ± 0.4% to 5.4 ± 0.3%, LDL cholesterol from 113 ± 30.4 to 106 ± 28 mg/dL, and triglycerides from 123.6 ± 56.1 to 119.2 ± 44.5 mg/dL, while HDL cholesterol and eGFR remained unchanged. Nausea was the most common adverse event (7.8%), and treatment discontinuation occurred in 10.4%, mainly among individuals previously treated with GLP-1 receptor agonists. Low-dose tirzepatide resulted in clinically meaningful short-term weight loss and favorable metabolic effects, supporting its effectiveness and tolerability in real-world practice.