Key result
Tirzepatide boosts adiponectin up to ~88% and lowers leptin versus placebo at 72 weeks.
Why the study?
The relationships among weight loss, abdominal adiposity, and metabolic improvements following tirzepatide treatment in Japanese adults with obesity disease without diabetes were not well characterized.
Does tirzepatide improve metabolic markers and reduce abdominal adiposity in Japanese adults with obesity disease without diabetes?
RCT (n=225)
1:1:1
Does tirzepatide improve metabolic markers and reduce abdominal adiposity in Japanese adults with obesity disease without diabetes?
Tirzepatide-induced weight loss is strongly associated with reductions in visceral adipose tissue and improvements in systemic metabolic and inflammatory markers in Japanese patients with obesity.
OBJECTIVES: This analysis characterized obesity-related outcomes in SURMOUNT-J and explored relationships among weight loss, abdominal adiposity, and metabolic improvements. METHODS: Japanese adults with obesity disease without diabetes were randomized (1:1:1) to tirzepatide (10 or 15 mg) or placebo plus lifestyle modification. Prespecified analyses evaluated changes from baseline to week 72 in obesity and glycemic parameters. Post hoc analyses assessed correlations among changes in weight, anthropometrics, abdominal adiposity (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], hepatic fat fraction [HFF]), and glycemic outcomes. RESULTS: Among 225 participants (placebo n=75; tirzepatide 10 mg n=73; 15 mg n=77), tirzepatide significantly increased high molecular weight adiponectin (mean change: 78.9% and 88.4% vs 0.9%) and reduced leptin (-57.3% and -63.1% vs -8.4%), high-sensitivity C-reactive protein (-55.1% and -65.3% vs -17.7%), and liver-related markers, including procollagen III (-21.3% and -24.8% vs -3.8%) and cytokeratin-18 (-59.8% and -62.0% vs -32.8%) (all P<.001). Glucose, insulin, and C-peptide AUC during a 75-g oral glucose tolerance test were also significantly reduced. At week 72, weight loss correlated linearly with reductions in adiposity. Weight loss was strongly correlated with VAT reduction (r=0.722-0.837 across groups), and VAT reductions strongly correlated with waist measures (r=0.837). Weight and VAT reductions showed moderate correlations with reductions in glucose, insulin, and C-peptide AUC (r=0.378-0.656). CONCLUSION: Tirzepatide-induced reductions in body weight and VAT were associated with improvements in metabolic markers and glucose metabolism. Strong associations between anthropometric measures and VAT support their use as surrogate markers of visceral adiposity in Japanese patients with obesity disease.
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Waki et al. (2026) conducted an RCT in obesity disease without diabetes (n=225). Tirzepatide vs. placebo plus lifestyle modification was evaluated on Changes from baseline to week 72 in obesity and glycemic parameters (e.g., high molecular weight adiponectin) (p=<.001). Tirzepatide significantly increased high molecular weight adiponectin (78.9% and 88.4% vs 0.9%) and reduced leptin (-57.3% and -63.1% vs -8.4%) compared to placebo at 72 weeks (all P<.001).
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