For decades, daily growth hormone injections have been an important part of care for people with Prader-Willi syndrome (PWS), helping improve growth, body composition, muscle mass, and overall health. More recently, long-acting growth hormone (LAGH) formulations have been developed to stay active in the body longer, allowing growth hormone to be given as little as once a week instead of every day. These formulations offer a more convenient alternative to daily treatment.
A newly published meta-analysis in children with growth hormone deficiency found that long-acting growth hormone produced similar growth compared with daily growth hormone, but was associated with a greater increase in body mass index (BMI) during the first year of treatment. Because the studies did not directly measure changes in body fat and lean muscle mass, researchers cannot determine what caused the increase in BMI—or whether the finding applies to people with PWS.
Read the Publication: Long-acting growth hormone for treating growth hormone deficiency in children: a meta-analysis of randomized controlled trials focusing on changes in body mass index
What Did the Study Find?
Researchers reviewed data from 585 children with growth hormone deficiency who participated in clinical trials comparing long-acting and daily growth hormone. Children receiving weekly growth hormone grew similarly to those receiving daily injections, but experienced a significantly greater increase in BMI during the first year of treatment. The increase in BMI was relatively modest and occurred primarily during the first year, with no additional increases seen after that point in the longer-term data.
BMI alone cannot tell us whether children gained more body fat, more lean muscle mass, or a combination of both. The studies did not directly measure changes in fat and lean mass, leaving an important question unanswered.
What Does This Mean for People with PWS?
We don't know yet.
None of the participants in this meta-analysis had PWS. While long-acting growth hormone is being considered for use in conditions including PWS, the evidence specific to PWS remains limited. That distinction matters because PWS is associated with unique challenges related to body composition, metabolism, appetite regulation, and obesity risk. Findings from children with growth hormone deficiency cannot automatically be applied to people with PWS.
One possible explanation for the BMI findings in this paper relates to how long-acting growth hormone works. With daily growth hormone injections, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) rise and fall together. With long-acting formulations, however, GH levels may decline after the first few days following an injection, while IGF-1 remains elevated throughout the week.
The authors suggest that prolonged IGF-1 exposure in the absence of a strong GH signal could contribute to the increase in BMI seen in these studies. Previous studies of IGF-1 treatment have also reported increases in body fat, providing additional support for this hypothesis. However, the studies included in this review did not directly measure changes in fat mass and lean muscle mass, so the underlying cause of the BMI increase wasn’t determined here.
Importantly, the increase in BMI observed in children with growth hormone deficiency appeared to be relatively modest and occurred primarily during the first year of treatment, with no additional increases seen after that point. The researchers also emphasized that future studies are needed to determine whether similar effects occur in other conditions treated with growth hormone, including PWS.
Additional Research Is Needed
Growth hormone treatment in PWS is about much more than increasing height. It is also used to improve muscle mass, reduce body fat, support physical function, and promote overall health.
Before LAGH can be considered equivalent to daily treatment in PWS, researchers need to understand how weekly formulations affect body composition, metabolism, appetite, and other outcomes that are particularly important for individuals with PWS.
The convenience of a weekly injection is appealing for many families. However, this new study highlights the need for dedicated research in PWS so that families and clinicians can make informed decisions based on evidence specific to the syndrome.
For now, the jury is still out. Daily growth hormone remains the approach with the strongest evidence base in PWS, while important questions about the long-term effects of long-acting growth hormone in PWS remain unanswered.
