Effects of <scp>glucagon‐like</scp> peptide‐1 analogue treatment in genetic obesity: A case series

Welling, Mila S; Groot, C. J. De; Kleinendorst, Lotte; Voorn, Bibian van der; Burgerhart, Jan S.; Valk, Eline S van der; Haelst, Mieke M. van; Akker, Erica van den; Rossum, Elisabeth F.C. van

doi:10.1111/cob.12481

Cited by 18 publications

(12 citation statements)

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“…The increase in BMI is similar to another study reporting the weight outcome after two and 3 years of follow-up in 15 patients with POMC deficiency and 9 patients with LEPR deficiency [8]. Future studies are needed to evaluate the longer-term beneficial effects and adverse side-effects of MC4R agonists, as well as the role of other effective treatment options, such as the nontargeted anti-obesity agents glucagon-like peptide-1 agonists or naltrexone-bupropion [9][10][11].…”

Section: Discussionsupporting

confidence: 77%

The Narrative of a Patient with Leptin Receptor Deficiency: Personalized Medicine for a Rare Genetic Obesity Disorder

Welling¹,

Kleinendorst²,

Haelst³

et al. 2023

Obes Facts

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Leptin receptor (LEPR) deficiency is a rare genetic disorder that affects the body’s ability to regulate appetite and weight. For patients and their families, the disorder seriously disrupts daily life; however, little is published about this impact. We here report the experiences of a 10.5-year-old girl with leptin receptor deficiency and her family. The diagnosis of this rare genetic obesity had a deep impact on the life of the child and her family. It led to a better understanding of the cause of the impaired appetite regulation and early-onset obesity with subsequently less judgement by others and improved cooperation of their social network and school on maintaining a healthy lifestyle for this girl. A strict eating regimen and lifestyle measures resulted in the first year after diagnosis in a significantly decreased body mass index (BMI), followed by BMI stabilization, still categorized as obesity class three. However, the troublesome challenge of how to manage the disruptive behaviour due to hyperphagia remained. Eventually, due to treatment with targeted pharmacotherapy, i.e., melanocortin-4 receptor agonists, her BMI continued to decrease due to resolving hyperphagia. The daily routine of the family and the atmosphere at home positively changed as they were no longer dominated by the food-focused behaviour of the child and the adherence to the strict eating regimen. This case report demonstrates the importance and impact of a rare genetic obesity disorder diagnosis in a family. Additionally, it highlights the value of genetic testing in patients with a high suspicion of a genetic obesity disorder as it can eventually lead to personalized treatment, such as guidance by specialized healthcare professionals and educated caregivers or targeted pharmacotherapy.

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Section: Discussionsupporting

confidence: 77%

The Narrative of a Patient with Leptin Receptor Deficiency: Personalized Medicine for a Rare Genetic Obesity Disorder

Welling¹,

Kleinendorst²,

Haelst³

et al. 2023

Obes Facts

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“…Based on the success of GLP1 agonism in adolescents with common obesity 145 , studies were performed to investigate if it might be beneficial in patients with monogenic obesity. Indeed, in case reports, treatment with liraglutide induced weight loss (adipose mass and lean mass) and improved metabolic parameters in individuals with pathogenic variants of MC4R 146 – 148 .…”

Section: Treatments For Monogenic Obesitymentioning

confidence: 99%

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Körner

Fischer‐Posovszky

2022

Nat Rev Endocrinol

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Obesity is a multifactorial and complex disease that often manifests in early childhood with a lifelong burden. Polygenic and monogenic obesity are driven by the interaction between genetic predisposition and environmental factors. Polygenic variants are frequent and confer small effect sizes. Rare monogenic obesity syndromes are caused by defined pathogenic variants in single genes with large effect sizes. Most of these genes are involved in the central nervous regulation of body weight; for example, genes of the leptin–melanocortin pathway. Clinically, patients with monogenic obesity present with impaired satiety, hyperphagia and pronounced food-seeking behaviour in early childhood, which leads to severe early-onset obesity. With the advent of novel pharmacological treatment options emerging for monogenic obesity syndromes that target the central melanocortin pathway, genetic testing is recommended for patients with rapid weight gain in infancy and additional clinical suggestive features. Likewise, patients with obesity associated with hypothalamic damage or other forms of syndromic obesity involving energy regulatory circuits could benefit from these novel pharmacological treatment options. Early identification of patients affected by syndromic obesity will lead to appropriate treatment, thereby preventing the development of obesity sequelae, avoiding failure of conservative treatment approaches and alleviating stigmatization of patients and their families.

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“…In addition to the effects of dextroamphetamine, GLP-1 analogues slows gastric emptying and increase satiety, leading to a lower food intake ( 38 ). GLP-1 analogues have recently shown to be effective in reducing weight and hyperphagia in four adult patients with genetic HO ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

et al. 2022

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IntroductionHypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO.MethodsA retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment.ResultsNineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up.ConclusionIn addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results.

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Effects of glucagon‐like peptide‐1 analogue treatment in genetic obesity: A case series

Cited by 18 publications

References 34 publications

The Narrative of a Patient with Leptin Receptor Deficiency: Personalized Medicine for a Rare Genetic Obesity Disorder

The Narrative of a Patient with Leptin Receptor Deficiency: Personalized Medicine for a Rare Genetic Obesity Disorder

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

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