Work

SAT-675 The Impact of the Oral Growth Hormone Secretagogue Ibutamoren on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults With Overweight/Obesity

Year: 2025

Type: article

Abstract: Disclosure: N. Chamorro-Pareja: None. K.E. Corey: Intercept. M.S. Haines: BioAge. C.C. Dobbie: None. J. Lin: None. M.L. Chicote: None. J.S. Husseini: None. M.A. Bredella: None. L.E. Dichtel: Perspectum Diagnostics, Lumos Pharma, Recordati, Novo Nordisk, Third Rock Ventures, Marea Therapeutics, Merida Biosciences, Flare Therapeutics. Background: Daily, subcutaneous growth hormone (GH) administration has been demonstrated to reduce hepatic steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Ibutamoren is an investigational oral, small molecule GH secretagogue. We hypothesized that GH augmentation via ibutamoren would reduce intrahepatic lipid content (IHL) and improve body composition in a pilot study of individuals with MASLD. Methods: Thirteen adults with BMI ≥25 kg/m2 and MASLD without diabetes were enrolled in an open-label pilot study of daily oral ibutamoren 25 mg for 6 months (NCT05364684). The primary endpoint was absolute change in percent IHL by proton magnetic resonance spectroscopy. Secondary endpoints included absolute change in ALT, HbA1c and body composition by dual-energy x-ray absorptiometry. Data are reported as mean ± SD. The open-label pilot cohort was compared to a historical, prospective, placebo group studied under a similar protocol (NCT02217345). Results: Seven subjects completed the 6-month ibutamoren study (IBU) and were compared to 10 historical placebo controls (PBO) with similar mean weight change (IBU 1.7±2.8% vs PBO 2.9±1.9%, p=0.3). Baseline mean age (46±12 y), BMI (33±4 kg/m2), sex distribution (35% female) and IHL (17.1±13.8%) did not differ between IBU and PBO. IGF-1 Z-score was significantly augmented in IBU vs PBO, as expected (delta IGF-1 Z-score 0.9±0.5 vs -0.3±0.6, p<0.001). Three IBU subjects dropped out for treatment-emergent adverse events (n=2 hyperglycemia, n=1 brain fog). In an intent-to-treat analysis, there was no difference in absolute change in IHL in IBU vs PBO (3.9±6.7% vs 6.7±6.1%, p=0.4). Changes in serum ALT (8±18 IU/L vs 4±7 IU/L, p=0.6), appendicular lean mass (0.7±0.9 kg vs 1.0±0.6 kg, p=0.6) and visceral adipose tissue (-1.8±11.9 cm2 vs 5.3±13.0 cm2, p=0.3) did not differ in IBU vs PBO, respectively. HbA1c increased modestly within in the non-diabetic range in IBU vs PBO (5.3±0.2% to 5.7±0.4% vs 5.4±0.2% to 5.4±0.2%, p=0.008 for delta). In an as-treated secondary analysis excluding one IBU subject with suspected non-adherence to ibutamoren administration (based on lack of change in IGF-1 Z-score at 6 months), there was a beneficial effect on IHL in IBU vs PBO (1.5±2.3% vs 6.6±6.1%, p=0.03). All other findings were similar to the intent-to-treat analysis. Conclusion: In this pilot study, we demonstrated a possible beneficial signal of ibutamoren on IHL in an as-treated secondary analysis but were unable to demonstrate this effect in our primary analysis or an effect on body composition in either analysis. Future larger studies could investigate oral ibutamoren co-administered with weight loss medications such as GLP-1 receptor agonists, a combination which may offset the negative glycemic effect of ibutamoren while harnessing the potential for GH augmentation to further reduce liver fat and preserve muscle mass. Presentation: Saturday, July 12, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.1594