Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. hGH

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with Prader-Willi syndrome, 15 men and 22 women, n=37 randomised to 1 year of growth hormone (n=19) or placebo (n=18) followed by 2 years of growth hormone for all; median age 29.5, median baseline apnoea-hypopnoea index 1.4 events/h, so the group did not have obstructive sleep apnoea at entry

   Polysomnography every six months found no difference in any sleep or respiratory parameter between the growth hormone and placebo groups; sleep efficiency improved across the study in both arms, and the apnoea-hypopnoea index rose inconsistently while staying inside the normal range. The question this trial was built to answer is whether growth hormone worsens breathing during sleep in Prader-Willi syndrome, not whether it treats obstructive sleep apnoea, and the participants did not have the condition at baseline. No trial of growth hormone in people who have obstructive sleep apnoea is on file.

   Source PubMed Central 1 primary source read for this row

2. Tirzepatide

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with moderate-to-severe obstructive sleep apnoea and obesity; trial 1 n=234 not on positive airway pressure (67.1% male, mean age 47.9, mean BMI 39.1), trial 2 n=235 on positive airway pressure (72.3% male, mean age 51.7, mean BMI 38.7); 52 weeks

   Two phase 3 double-blind placebo-controlled trials measured the apnoea-hypopnoea index directly at 52 weeks, at the maximum tolerated dose of 10 mg or 15 mg weekly. Against baseline means of 51.5 and 49.5 events per hour, the treatment difference from placebo was -20.0 events per hour in trial 1 and -23.8 in trial 2, and hypoxic burden, body weight, high-sensitivity C-reactive protein, systolic blood pressure and patient-reported sleep measures all moved with it. The FDA has approved tirzepatide, as Zepbound, to treat moderate to severe obstructive sleep apnoea in adults with obesity alongside a reduced-calorie diet and increased physical activity; both trials were funded by the manufacturer, and no trial in people who have obstructive sleep apnoea without obesity is on file.

   Source PubMed Central 2 primary sources read for this row

3. Urotensin II

   human observational Mechanistic only Not approved for this condition

   Who was studied

   89 people with obstructive sleep apnoea (66 men, mean age 52.5, median apnoea-hypopnoea index 39.0 events/h) and 89 matched controls (64 men, mean age 50.1); cross-sectional, enrolled April 2018 to April 2020

   Recorded, and not evidence for this condition

   Serum urotensin-II was measured, never administered: it was higher in the obstructive sleep apnoea group than in matched controls (3.41 against 2.18 ng/mL) and was associated with the apnoea-hypopnoea index, systolic blood pressure and high-sensitivity C-reactive protein. That is an association between a circulating peptide and disease severity in one cross-sectional sample. No study has given urotensin-II to a person with obstructive sleep apnoea, and nothing here measures what happens to sleep-disordered breathing when it is given.

   Source PubMed Central 1 primary source read for this row

Recorded absences

1 compound is listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. Progesterone

   No rung — nothing on file to grade Not approved for this condition

   The progestin literature for obstructive sleep apnoea tested medroxyprogesterone acetate, a synthetic progestin and a different molecule from progesterone. A Cochrane review of 26 randomised placebo-controlled trials covering 21 drugs in 394 participants found no significant beneficial effect for medroxyprogesterone. No trial of progesterone itself in obstructive sleep apnoea is on file, and the sleep evidence that does exist for progesterone concerns sleep continuity in postmenopausal women rather than breathing during sleep.

Checked, and nothing recorded

17 compounds were checked against obstructive sleep apnoea and produced no gradeable row.

• Agouti-Related Protein (AgRP) — checked, no row on file
• ARA-290 — checked, no row on file
• CART (Cocaine- and Amphetamine-Regulated Transcript) — checked, no row on file
• CJC-1295 DAC — checked, no row on file
• CJC-1295 no-DAC — checked, no row on file
• DSIP — checked, no row on file
• Epitalon — checked, no row on file
• Galanin — checked, no row on file
• Ipamorelin — checked, no row on file
• Melanotan II — checked, no row on file
• Neuropeptide Y — checked, no row on file
• Orexin-A — checked, no row on file
• Orexin-B — checked, no row on file
• Sauvagine — checked, no row on file
• Selank — checked, no row on file
• Semax — checked, no row on file
• Sermorelin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.