Endocrine Abstracts

Somapacitan is a once-weekly, long-acting growth hormone (GH) derivative approved for the treatment of adult GH deficiency (AGHD). Our objective was to evaluate the effects of somapacitan on glucose metabolism compared with daily GH or placebo in patients with AGHD using data from three previously published phase 3 trials: REAL 1 (NCT02229851), REAL 2 (NCT02382939) and REAL Japan (NCT03075644). REAL 1 was a randomised, placebo-controlled (double-blind) and active-controlled (open-label) trial in GH-naïve patients, who received somapacitan (n=120), daily GH (n=119) or placebo (n=61) for 34 weeks (main phase). In a subsequent 52-week extension (86 weeks of treatment in total), patients receiving somapacitan continued with somapacitan (n=114), patients receiving daily GH were re-randomised to receive either somapacitan (n=51) or daily GH (n=52), and patients receiving placebo were switched to somapacitan (n=55; not included in this analysis). REAL 2 and REAL Japan were randomised, open-label, active-controlled trials in patients previously treated with daily GH. In REAL 2, patients received somapacitan (n=61) or daily GH (n=31) for 26 weeks. In REAL Japan, patients received somapacitan (n=46) or daily GH (n=16) for 52 weeks. In these post hoc analyses, the absolute or relative change from baseline between treatments for HbA1c, fasting plasma glucose (FPG), fasting serum insulin and index of insulin resistance (HOMA-IR) was explored. In treatment-naïve patients (REAL 1), there were no statistically significant (P<0.05) differences between somapacitan and placebo for any glucose-related endpoints at week 34 (main phase). No statistically significant differences in HbA1c were observed between somapacitan and daily GH at week 34 or week 86 (main phase plus extension). Transient differences were seen at week 34 between somapacitan and daily GH (with higher values reported for daily GH) for FPG (estimated treatment difference [95% CI]: –0.16 mmol/l [–0.30; –0.03]), fasting serum insulin (estimated treatment ratio [ETR] [95% CI]: 0.85 [0.73; 0.99]) and HOMA-IR (ETR [95% CI]: 0.80 [0.69; 0.94]); these differences were not seen at week 86. In previously treated patients (REAL 2, REAL Japan and REAL 1 patients who received daily GH in the main phase and were re-randomised for the extension), no statistically significant differences were seen between treatments for any glucose-related endpoints. No new cases of diabetes were reported in somapacitan-treated patients in these trials. In conclusion, somapacitan was similar to daily GH and had no clinically relevant adverse effects on glucose metabolism in treatment-naïve or previously treated patients with AGHD in these phase 3 trials.