Description

Most organisms display endogenously produced rhythms in physiology and behavior of ~24 hours in duration. These rhythms, termed circadian rhythms, are entrained to precisely 24 hours by the daily extrinsic light–dark cycle. Circadian rhythms are driven by a transcriptional–translational feedback loop that is hierarchically expressed throughout the brain and body; the suprachiasmatic nucleus of the hypothalamus is the master circadian oscillator at the top of the hierarchy.

Precise timing of the circadian clocks is critical for many homeostatic processes, including energy regulation and metabolism. Many genes involved in metabolism display rhythmic oscillations. Because circadian rhythms are most potently synchronized with the external environment by light, exposure to light at night potentially disrupts circadian regulation. Other potential disruptors of circadian organization include night shift work, social jet lag, restricted sleep, and misaligned feeding.Each of these environmental conditions has been associated with metabolic changes and obesity. The goal of this review is to highlight how disruption of circadian organization, primarily due to night shift works and exposure to light at night has downstream effects on metabolic function. Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration in August 2021 for the treatment of pediatric growth hormone deficiency (GHD). Lonapegsomatropin is a prodrug consisting of unmodified GH transiently conjugated to methoxypolyethylene glycol which enables time-release of GH with a half-life of ∼ 25 hours allowing for once-weekly administration.
 Clinical trials of lonapegsomatropin have demonstrated positive efficacy results in children (phase 2 and 3) and adults (phase 2) with GHD. The phase 3 trial in children with GHD established non-inferiority and statistical superiority of height velocity with lonapegsomatropin (11.2 cm/yr) compared to daily GH (10.3 cm/yr), with no concerning side effects with lonapegsomatropin. Similar growth responses have been reported in other LAGH products in phase 2 (somapacitan) and phase 3 (somatrogon) trials. Lonapegsomatropin is distributed in temperature-stable, prefilled cartridges at 9 different doses that can be prescribed based upon specific weight brackets designed to deliver approximately 0.24 mg/kg/wk. An electronic delivery device is required to combine the powdered medication with the diluent and deliver the medication subcutaneously through a small gauge needle to the recipient.

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With Regards
Michelle

Journal Coordinator
Journal of Reproductive Endocrinology & Infertility