A real-world study of tirzepatide for weight loss in adults without diabetes mellitus.
Angelopoulos. Nikolaos N; Androulakis. Ioannis I; Rizoulis. Andreas A; Boniakos. Anastasios A; Fousteris. Evangelos E; Mentzelopoulou. Voula V; Petkova. Valentina V; Paparodis. Rodis R; Zianni. Dimitra D; Florakis. Dimos D; Korakovouni. Areti A; Mouslech. Zadalla Z; Livadas. Sarantis S; Tzoulis. Ploutarchos P
Key Findings
- Lowâdose tirzepatide (2.5â5â¯mg weekly) produced an average 7.3â¯% weight loss over 12 weeks.
- 46â¯% of participants achieved â¥5â¯% weight loss, a clinically meaningful threshold.
- Modest metabolic benefits were seen: HbA1c fell from 5.6â¯% to 5.4â¯%, LDL dropped slightly, triglycerides unchanged, HDL and eGFR stable.
- Nausea was the most common adverse event (7.8â¯%); 10.4â¯% stopped treatment, mainly those previously on GLPâ1 agonists.
Practical Outcomes
- For biohackers looking for a shortâterm, lowâdose tirzepatide protocol, 5â¯mg weekly for about three months appears to be effective for noticeable weight loss with manageable side effects. Starting at 2.5â¯mg for a week can help gauge tolerance before titrating up. Expect modest improvements in glucose and lipid markers, but monitor for nausea and consider prior GLPâ1 exposure as a risk factor for discontinuation.
Summary
A 12âweek realâworld trial gave people with obesity but no diabetes a low dose of tirzepatide (starting at 2.5â¯mg, then 5â¯mg weekly). On average they lost about 7â¯% of their body weight (â8â¯kg) and almost half lost at least 5â¯% of their weight, with small improvements in blood sugar and cholesterol and few side effects.
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.
Study Information
pubmed
2025
2025-12-08T00:00:00.000Z
10.1038/s41366-025-01986-0