Setmelanotide may cut metabolic syndrome risk in rare monogenic forms of obesity
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Key takeaways:
- People with rare monogenic obesity had reduced metabolic syndrome scores at 1 year after treatment with setmelanotide.
- Weight-loss achievers exhibited a greater decrease in metabolic syndrome score.
DALLAS — People with rare monogenic forms of obesity may reduce their risk for metabolic syndrome with setmelanotide therapy, according to research presented at ObesityWeek.
Using data from two phase 3 trials, researchers analyzed the impact of setmelanotide (Imcivree, Rhythm Pharmaceuticals), a melancortin-4 receptor agonist, on severity of metabolic syndrome in children and adults with obesity related to proopiomelanocortin (POMC) deficiency or leptin receptor (LEPR) deficiency. Results showed a decrease in metabolic syndrome score after 1 year of treatment, with a greater reduction in those who met their predetermined weight threshold at 1 year.
“One year of treatment was associated with decreased metabolic syndrome score based on BMI in [people with] POMC and LEPR deficiencies, suggesting that intervention may reduce the risk of future cardiovascular disease and type 2 diabetes with rare genetic diseases of obesity,” James Swain, MD, medical director at Honor Health Research Institute in Scottsdale, Arizona, said during a presentation.
Researchers conducted a post hoc analysis of children and adults with POMC or LEPR deficiency who received setmelanotide for 1 year as part of a phase 3 trial. Swain and colleagues calculated metabolic syndrome risk using the metabolic syndrome score based on BMI (MetS-Z-BMI score), a measurement that estimates risk and severity of metabolic syndrome. Weight-loss achievers at 1 year were defined as adults who had a 10% or greater reduction in weight from baseline to 1 year or children with a 0.3 or greater decrease in BMI z score at 1 year.
The current study included 10 people with POMC deficiency and eight with LEPR deficiency. Nine participants were adults aged at least 18 years and nine were children aged 10 to 17 years.
At baseline, each 1-point increase in MetS-Z-BMI score was associated with increased risk for cardiovascular disease (OR = 3.9) and type 2 diabetes (OR = 4.6) among adults. The same finding was observed in children, with increased risk for CVD (OR = 13.3) and type 2 diabetes (OR = 3.7) with each 1-point increase.
Fourteen participants achieved their 1-year weight threshold; four did not reach their threshold. Those who achieved their target weight loss at 1 year had a 1.3-point decrease in MetS-Z-BMI score compared with a 0.17-point decrease for nonachievers (P = .0187). Those with POMC deficiency had a 1.45-point decrease in MetS-Z-BMI score from baseline to 1 year compared with a 0.56-point decrease for people with LEPR deficiency (P = .0278). Changes in MetS-Z-BMI score were similar between males and females and between children and adults.
Although participants who achieved their weight threshold had greater decreases in MetS-Z-BMI score, Swain noted that all but one person in the study was able to decrease their score after treatment.
“Despite not being achievers for weight loss, three out of four nonachievers exhibited a reduction in MetS-Z-BMI score, indicating there’s maybe some other impact of setmelanotide beyond weight loss,” Swain said.
Swain said the study had several limitations, including the lack of a control group and how higher metabolic syndrome scores may be exhibited by people with metabolic parameters in the upper range of normal.
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Wabitsch M, et al. Oral-065. Presented at: ObesityWeek; Oct. 14-17, 2023; Dallas.
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