June 28, 2016
3 min read

Relamorelin improves diabetic gastroparesis symptoms

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Adults with diabetic gastroparesis experienced accelerated gastric emptying and reduced vomiting with 10 µg of subcutaneous relamorelin administered twice daily, according to phase 2 trial data.

Relamorelin (RM-131, Rhythm Pharmaceuticals) “is a novel synthetic pentapeptide amide that acts as a potent ghrelin-receptor agonist, with similar characteristics to native ghrelin, but with enhanced potency, plasma stability, and circulating half-life,” Anthony Lembo, MD, from Beth Israel Deaconess Medical Center in Boston, Michael Camilleri, MD, from the Mayo Clinic in Rochester, Minn., and colleagues wrote. Previous studies have shown the agent has potent prokinetic effects, they added.

Anthony Lembo

Michael Camilleri

The researchers performed a double blind trial involving 204 patients with diabetic gastroparesis from 27 clinical centers (78% white; 67% women; mean age, 55 years; 88% with type 2 diabetes; mean BMI > 30 kg/m2). All patients had moderate-to-severe symptoms and delayed gastric emptying and were randomly assigned to receive placebo or 10 µg of subcutaneous relamorelin once or twice daily for 28 days.

Gastric emptying half-time determined by the C-spirulina gastric emptying breath test (GEBT, AB Diagnostics) served as the primary endpoint. Nausea, abdominal pain, bloating, and early satiety were evaluated individually and with a composite score, and vomiting frequency and severity, safety and tolerability were also evaluated.

Patients who received the twice-daily dose of relamorelin experienced significantly accelerated gastric emptying compared with placebo (P < .03). Moreover, their vomiting frequency was reduced by 63% and vomiting severity was reduced by 58%, which was significant compared with placebo (P ≤ .033). However, relamorelin did not significantly improve other GI symptoms compared with placebo.

Among the 58.3% of patients with vomiting at baseline, the twice-daily dose of relamorelin significantly reduced gastric emptying half-time and vomiting, as well as the composite score of nausea, abdominal pain, bloating and early satiety compared with placebo (P = .043).

Relamorelin was well tolerated and showed a safety profile similar to placebo. The most common treatment-emergent adverse events in the relamorelin-treated patients were headache and worsening of pre-existing diabetes.

“In patients with type 1 or type 2 diabetes mellitus and gastroparesis, compared with placebo, relamorelin 10 µg twice daily significantly improved gastric emptying and vomiting, [and] in the subgroup of patients with vomiting during the baseline period ... the effects of relamorelin extended beyond significantly improving gastric emptying and vomiting to include significantly improving nausea, abdominal pain, bloating, and early satiety,” the researchers concluded.

Pankaj Jay Pasricha

The improvement in gastric emptying from baseline shown in this trial “is modest at best (about 10% over placebo) and it is not known whether this is due to gradual desensitization of the receptor over this period of time as the acute response is much more impressive,” Pankaj Jay Pasricha, MD, from Johns Hopkins University School of Medicine in Baltimore, and William Snape, MD, from California Pacific Medical Center in San Francisco, wrote in a related editorial.

While the data also show relamorelin may potentially improve other symptoms, “confirmation in prospective trials with the appropriate primary endpoints remains to be seen and is certainly not a ‘slam-dunk’ given the negative results of a previous ghrelin agonist despite also having a promising start,” they added. “Furthermore, despite understandable enthusiasm in the gastroenterological community for the promotility effects of ghrelin, it should not be forgotten that ghrelin is a potent and pleiotropic hormone with a variety of systemic effects mediated by receptors expressed in the brain, pancreatic islets, heart, and a variety of other normal and neoplastic tissues.” – by Adam Leitenberger

Disclosures: This study was funded by Rhythm Pharmaceuticals. Camilleri reports he has received grants from Mayo Clinic and Rhythm Pharmaceuticals during the conduct of this study. Lembo reports he has received grants from Beth Israel Deaconess Medical Center during the conduct of the study, has received personal fees from Ironwood and Allergan, and grants and personal fees from Prometheus unrelated to this study. Please see the full study for a list of all other researchers’ relevant financial disclosures. Pasricha reports he is a co-founder of Neurogastrx and Orphomed, receives research funding from Theravance Biopharma, and serves as a consultant to Vanda Pharmaceuticals, SK Life Sciences and Ardelyx. Snape reports no relevant financial disclosures.