Two treatments show an early promise for hypothalamic obesity


Two different agents showed potential to safely treat patients with hypothalamus obesity in two pilot studies with a small number of patients.

One to study prospectively randomized 21 adults with acquired hypothalamic obesity to placebo or Tesomet treatment, a compound that combines the new inhibitor of thesofensin monoamine reuptake with metoprolol, an added beta-blocker to protect against the adverse effects of tesofensin on heart rate and heart contractility. After 24 weeks of treatment, people taking tesofensin / metoprolol had significant weight loss compared with controls, while showing good tolerance with no significant effects on heart rate, blood pressure, or heart rate. Ulla Feldt-Rasmussen, MD, DMSc, was reported at the annual meeting of the Endocrine Society.

He second report reviewed 18 children and adolescents with acquired hypothalamic or genetic obesity who received open-label treatment dextroamphetamine for an average of 20 months, and overall patients safely lost an average of 0.43 in the body mass index (BMI) standard deviation score. Jiska van Schaik, MD, in an independent talk at the meeting.

A supplement for lost satiety

Patients with hypothalamic obesity face a dual problem arising from hypothalamic dysfunction treated with tesofensin, Tesomet’s weight loss agent that increases hypothalamic levels of dopamineFeldt-Rasmussen, a professor of medical endocrinology at the University of Denmark and Rigshospitalet in Copenhagen, explains serotonin and norepinephrine by blocking the collection and thus quenching appetite and food cravings, while increasing fat metabolism. Currently, no treatment has regulatory approval to treat any form of hypothalamic obesity.

Thesofensin works as “a supplement for the loss of satiety, and satiety is what is lost” in patients with hypothalamic obesity, as well as in patients such as Prader-Willi syndrome, the two disorders of which tesofensin / metoprolol is currently being tested. “That’s the reason, and it seems to work,” he stated during his talk. The formulation contains 0.5 mg of tesofensin and 50 mg of metoprolol administered orally once daily.

He to study, aimed at Rigshospitalet, to 21 random patients aged 18 to 75 years and with a BMI of at least 27 kg / m2that they had all acquired hypothalamic obesity secondary to hypothalamic damage after cancer treatment. Patients had an average age of about 45 years, three-quarters were women, and their mean BMI was about 37 years., with 90% with a BMI of at least 30.

Study design requires 48-week follow-up; Feldt-Rasmussen presented the provisional results after 24 weeks, with 18 of the 21 patients enrolled remaining in the study for 24 weeks. Three patients left the task due to adverse events: one in the placebo arm and two who received tesofensin / metoprolol.

Weight fell an average of 6.6 kg from baseline among the 11 patients who completed 24 weeks of tesofensin / metoprolol treatment, compared with no mean change from baseline among the seven patients who completed baseline. placebo study, a significant difference. The researchers measured a validated compound satiety score every 4 weeks and found significantly more improvement among patients with tesofensin / metoprolol than those who received placebo during the first half of the study, but subsequently the mean scores of patients treated. actively fell to the same level of modest improvement as in placebo patients.

Despite this, mean weight loss in patients with tesofensin / metoprolol steadily increased over the full 24 weeks.

Safety measures of diastolic blood pressure, heart rate, and corrected QT interval showed no significant differences between groups. Systolic pressure showed a transient mean increase of 4 mm Hg above the initial value in the thesofensin / metoprolol group, compared with a small decrease in control patients, but at 24 weeks the mean systolic blood pressure had recovered closer to baseline levels in both subgroups and showed no significant difference between groups. Two patients with tesofensin / metoprolol developed serious adverse events. In one patient, these were unrelated to treatment. The other patient developed anxiety after eight weeks that was possibly related to treatment, but continued on treatment. Other side effects with tesofensin / metoprolol include dizziness, sleep disorder, and dry mouth, but they were all mild and patients were willing to tolerate them to achieve their weight loss, Feldt-Rasmussen said.

Reuse of an ADHD treatment

Dextroamphetamine increases satiety and increases resting energy expenditure and is common treatment per Attention Deficit Hyperactivity Disorder. van Schaik and his co-authors reviewed 13 children and adolescents with acquired hypothalamic obesity and 5 with genetic hypothalamic obesity who received treatment at either of the two Dutch hospitals during 2014-2020. Van Schaik, a researcher at the University Medical Center and Wilhelmina Children’s Hospital in Utrecht, the Netherlands, said the 18 patients took dextroamphetamine after other interventions failed to improve. Patients had an average of about 13 years of age.

In addition to an overall effect on the weight of the 18 subjects, the researchers found that they could subdivide the entire cohort into 10 respondents (56%), 4 (22%) with weight stabilization at treatment, and 4 individuals. who did not respond (22%) who continued to gain weight despite treatment. The 10 patients who responded had a mean drop in BMI standard deviation score of 0.91. The 10 users who responded had acquired hypothalamic obesity and increased by an average of 12.5 percentage points in the level of resting energy expenditure, compared to baseline, while in treatment. All four whose weight stabilized at treatment included three patients with genetic hypothalamic obesity. The four non-responders were divided into two with acquired hypothalamic obesity and two with the genetic form.

Thirteen patients (72%) had improvements in hyperphagia, energy, and behavior, and no patients had a serious adverse effect. One patient left treatment a month later due to high blood pressure.

“Dextroamphetamine can be promising, especially for acquired hypothalamic obesity,” concluded van Schaik, who added that prospective and controlled assessments are needed and that a healthy lifestyle is the foundation of the treatment of hypothalamic obesity.

The Tesomet studio was sponsored by Saniona, the company that develops Tesomet. Feldt-Rasmussen is Saniona’s advisor and some of the study’s co-authors are Saniona employees. van Schaik had no disclosures.

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