Changes in Abdominal Adiposity and Associations With Metabolic Health Markers Following Tirzepatide in Japanese Participants With Obesity Disease: Results From the SURMOUNT-J Study.

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.