During the first year, ibutamoren resulted in a significant 1.8-fold increase in 24-h mean GH levels and a 1.5-fold increase in serum IGF-1 levels. Increases in leptin and leptin/body fat ratio may promote earlier satiety and confer further benefit to patients seeking to alter their body composition. This change in weight was attributed to mild fluid retention that was noted with the ibutamoren treatment arm that resolved with treatment cessation. Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues (i.e., induce the secretion) of growth hormone (GH). Furthermore, ipamorelin has significant adipogenic effects and causes significant weight gains early in treatment that stabilizes over time. At 2 weeks, serum leptin levels were increased with ipamorelin compared to saline-treated controls and an increase in cumulative food intake during the first week. DEXA scans in GH-intact mice revealed that ipamorelin increased total body fat percentages compared to saline-treated controls while GH had no effect. After 9 weeks, body weight in the GH-deficient mice increased by 15.3% in those treated with ipamorelin compared to 95.5% in those treated with GH. Beck et al. evaluated ipamorelin’s effects on POI in bowel resection patients via a multicenter, double-blinded, placebo-controlled trial (59). Similar to the first study, the authors observed increases in GH and prolactin levels throughout the night, and in ACTH and cortisol levels during the first half of the night. A final study by these authors examined sleep in 7 healthy males treated with hexarelin and placebo either 1 week before or after hexarelin administration. No significant changes in sleep patterns were observed for any non-intravenous GHRP-6 formulations(60). Several additional studies examined how dosage and route of administration affected sleep patterns, and compared the sleep-endocrine effects of GHRPs in 7 subjects given 300 mg/kg GHRP-6 orally, in 7 subjects given 30 mg/kg GHRP-6 intranasally, and in 9 subjects given 30 mg/kg GHRP-6 sublingually. Ipamorelin binds exclusively to GHS-R1a receptors, which means it activates only one of several pathways capable of triggering GH release. Ipamorelin is a selective ghrelin receptor agonist designed to stimulate GH release without activating cortisol or prolactin pathways, which makes it exceptionally clean but limits its standalone amplitude. Click here to learn more about sermorelin therapy for women in Anaheim. Learn more about sermorelin therapy for men in Anaheim. A two-month randomized, double-blind, parallel, placebo-controlled trial with 24 men showed a 3kg increase in fat free mass (FFM) in the ibutamoren group when compared with placebo (P 56). After a 14–21 day washout period, the other treatment (placebo for the ibutamoren group and ibutamoren for placebo group) was given during the second week of the second 14 day period of caloric restriction. Ibutamoren mesylate has also been used in the setting of GH deficient children, but not as extensively as the GHRPs, with a single study demonstrating increases in GH and IGF-1 levels after only 7 days of therapy, without examining growth rates(43). A third study evaluating GHRP-2 in doses of 5–15 mcg/kg two or three times per day in 15 children with short stature further confirmed the previously observed increases in growth velocity following treatment. No adverse effects of L-163,191 were observed during this 14 day study, and the drug entered clinical development as MK-0677, also known as ibutamoren mesylate. This original GHRP mimics growth hormone releasing hormone (GHRH), but was found to only weakly stimulate GH secretion in vitro(23). The specific modifications — particularly the Aib (alpha-aminoisobutyric acid) and D-2-Nal residues — are what give ipamorelin its selectivity. A starting dose of 25 mg by mouth daily for ibutamoren is recommended given that this is the dose studied in randomized controlled trials. We recommend a starting dose of 0.1 mg of the GHRPs, which is well tolerated and efficacious in raising IGF-1 levels. Receptor desensitization occurs when repeated stimulation of ghrelin receptors causes downregulation — reducing the number of active receptors available to respond to subsequent doses. If cortisol or prolactin rises during a stack, it indicates the presence of a less-selective peptide like GHRP-2, GHRP-6, or hexarelin — not ipamorelin. Clinical trials confirm that ipamorelin alone and ipamorelin + CJC-1295 stacks produce no measurable cortisol or prolactin elevation at standard research doses. Acute GH pulses occur within 30–60 minutes of administration, but sustained IGF-1 elevation — the biomarker most correlated with anabolic outcomes — requires repeated dosing over multiple weeks. The most common and research-validated ratio is 200 mcg ipamorelin paired with 100 mcg CJC-1295 NO DAC, administered in the same subcutaneous injection.
