Low-Dose Tirzepatide for Obesity: Comparative Efficacy of 2.5 mg Versus 5 mg in Non-Diabetic Japanese Adults

In a 6-month prospective cohort of 112 non-diabetic Japanese adults with obesity, the 2.5 mg and 5 mg weekly tirzepatide doses produced similar weight loss (about 15–16% mean body weight) and similar rates of the composite success outcome, but fewer adverse events occurred with 2.5 mg. The authors conclude that low-dose tirzepatide may be a useful real-world strategy.

Journal article — Prospective multicentre non-randomised cohort study. Population: Non-diabetic Japanese adults aged 18–65 with BMI ≥30 kg/m² or ≥27 kg/m² with comorbidities. Sample size: 112 participants. Follow-up: 6 months. Interventions: tirzepatide 2.5 mg weekly; tirzepatide 5 mg weekly; standardised dietary and exercise counselling.

At 6 months, the primary outcome was achieved in 62.1% of the 2.5 mg group and 63.0% of the 5 mg group (HR 0.93, 95% CI 0.58–1.49; p = 0.772). Mean percent weight loss was -15.3% with 2.5 mg and -16.1% with 5 mg (p = 0.563). Reductions in BMI, skeletal muscle mass, and bone mass were similar between groups. Dietary adherence was 96.4% in both groups, whereas exercise adherence was 37.5%. Adverse events were more common with 5 mg (50% vs 35%), mainly gastrointestinal symptoms.

For researchers studying tirzepatide, this paper provides real-world evidence that lower maintenance doses may achieve similar 6-month weight loss with better tolerability in a Japanese population. It does not establish causal equivalence because dose assignment was not randomised, and it does not address cardiometabolic outcomes or longer-term weight maintenance.

Key findings

Primary outcome was achieved in 62.1% of the 2.5 mg group versus 63.0% of the 5 mg group (HR 0.93, 95% CI 0.58–1.49; p = 0.772).
Mean percent weight loss was -15.3% with 2.5 mg versus -16.1% with 5 mg (p = 0.563).
Adverse events were more frequent with 5 mg (50% vs 35%), primarily gastrointestinal symptoms.
Dietary adherence was 96.4% in both groups, while exercise adherence was 37.5%.
Reductions in BMI, skeletal muscle mass, and bone mass were similar between the two doses.

Limitations

Non-randomised design with dose assignment based on shared decision-making may introduce confounding.
No placebo or untreated control group.
Short 6-month follow-up limits assessment of long-term efficacy and safety.
Findings are limited to non-diabetic Japanese adults, reducing generalisability to other populations.

The record

Journal: Diabetes, obesity & metabolism
Published: 2026-07-28
PMID: 42521631 — DOI: 10.1111/dom.71162
Author countries: Japan

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.