Oral Macimorelin Deemed Safe, Effective Test for Diagnosing Adult Growth Hormone Deficiency

August 15, 2018

A new orally administered diagnostic test for adult human growth hormone deficiency also may prove more convenient for patients and clinicians.

Macimorelin displayed comparable accuracy, effectiveness, and safety compared with the insulin tolerance test in diagnosing patients with adult growth hormone deficiency (AGHD), according to a recent study published in the Journal of Clinical Endocrinology & Metabolism.

The glucagon stimulation test has long been considered the gold standard of growth hormone stimulation tests (GHST) with clinicians employing other notable tests such as the insulin tolerance test (ITT), arginine with growth hormone-releasing hormone (GHRH) and arginine with L-Dopa to measure the rate of GH release. However, these tests aren’t without drawbacks;  ITT in particular can cause complications among older patients with a history of heart disease or seizures.

“Other alternative provocative tests such as the arginine plus GHRH, arginine alone, and glucagon stimulation tests are either not available in the United States or have substantial limitations, including requiring intramuscular administration, a long duration, and/or low accuracy,” Jose M. Garcia, MD PhD, and his colleagues wrote in the study. “Thus, an unmet medical need remains for alternative GHSTs that are safe and reliable and have been approved by a regulatory authority.”

Macimorelin vs ITT

To determine whether macimorelin acetate, an oral ghrelin receptor agonist, compared with the ITT, the investigators performed an open-label, randomized, multicenter, two-way crossover, phase III study of 166 patients with suspected AGHD and healthy matched controls. The investigators grouped the patients based on high (38 patients), intermediate (37 patients) and low (39 patients) likelihood of AGHD and compared them with 25 patients in a healthy matched control group.

The investigators randomized patients to receive both tests between 7 days and 30 days apart, with patients receiving a dose of oral macimorelin at 0.5 mg/kg relative to their body weight or intravenous 0.1 U/kg of insulin.

A priori cutoff points for GH at first attempt were 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITT. Results showed tests were 99% evaluable in the macimorelin group and 82% in the ITT group with a negative agreement of 95.38% (95% CI, 63%-84%), positive agreement of 74.32% (95% CI, 87%-99%), sensitivity of 87% and specificity of 96%. On a subsequent retest, the macimorelin group had a 97% reproducibility rate.

After adjusting the tests to have an a priori cutoff of 5.1 ng/mL for both groups to limit the potential of a false diagnosis, the investigators found a negative agreement of 94% (95% CI, 85%-98%), positive agreement of 82% (95% CI, 72%-90%), sensitivity of 92% and specificity of 96%. The investigators reported no “serious adverse events” in the macimorelin group.

“The safety profile of macimorelin is particularly favorable compared with the ITT, which has potential for inducing severe side effects such as hypoglycemia-related seizure and exacerbation of cardiovascular and cerebrovascular disease,” Dr. Garcia and colleagues wrote. “From a clinician’s perspective, the macimorelin test is also more convenient, less time-consuming, and less resource-intensive than the ITT.”

The investigators noted results were promising, but also said oral macimorelin may not always be “an appropriate substitute test for the ITT or other provocative tests,” particularly in cases of older patients or patients with uncontrolled diabetes.

Reference: Jose M Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab. 2018;103:3083-3093. https://doi.org/10.1210/jc.2018-00665.