ECE2022 Oral Communications Oral Communications 4: Pituitary and Neuroendocrinology 1 (6 abstracts)
Significant weight loss resulted in reduced levothyroxine requirements during a tesomet trial of hypopituitary patients with acquired hypothalamic obesity
Marianne Klose 1 , Kim Huynh 1 , Jacob Tfelt 2 , Kim Krogsgaard 3 , Jørgen Drejer 3 , Sarah Byberg 4 , Sten Madsbad 5 , Faidon Magkos 6 , Abdellatif Aharaz 7 , Berit Edsberg 3 , Arne Astrup 8 & Ulla Feldt-Rasmussen 1
1Copenhagen University Hospital, Rigshospitalet, Dept of Endocrinology and Metabolism, Copenhagen, Denmark; 2Copenhagen University Hospital, Rigshospitalet, Dept of Cardiology, Copenhagen, Denmark; 3Saniona A/S, Glostrup, Denmark; 4Copenhagen University Hospital, Department of Biomedical Sciences, Copenhagen, Denmark; 5Copenhagen University Hospital, Hvidovre, Dept of Endocrinology and Metabolism, Copenhagen, Denmark; 6Copenhagen University, Department of Nutrition, Exercise and Sports (NEXS), Frederiksberg, Denmark; 7Slagelse Hospital, Dept of Endocrinology and Metabolism, Slagelse, Denmark; 8Novo Nordisk Foundation, Hellerup, Denmark
Objective: Hypothalamic obesity results in severe weight-gain and increased risk of cardiovascular and metabolic mortality. We aimed to assess the safety and efficacy of Tesomet (tesofensine plus metoprolol), and ongoing requirements in pituitary hormone replacement adjustments in adults with acquired hypothalamic obesity, a rare disease with no approved therapy
Research design, patients and methods
Twenty-one adults with hypothalamic obesity (16 females, 5 males, mean(SD) age 46(14.6) years; 90% with a BMI "≥" 30 kg/m2) were randomized to Tesomet (0.5 mg tesofensine/50 mg metoprolol)(n=14) or placebo (n=8) during a 24-week double-blind treatment period. Seventeen subjects (11 Tesomet; 6 placebo) continued in 24-week open-label extension, all treated with Tesomet. Primary endpoint was safety; secondary endpoints included body weight and waist circumference. Almost half had a craniopharyngioma, 86% had undergone pituitary/hypothalamic surgery, 52% irradiation. All received one or more anterior pituitary hormone replacements. Trial NCT03845075.
Results: Most common adverse events were sleep disorders, dizziness, dry mouth, and headache; mostly of mild to moderate severity. No clinically meaningful changes in heart rate or blood pressure were observed. On completion of the double-blind period, mean change in body weight from baseline was -7.84 kg for the Tesomet group vs -0.34 kg for placebo (P=0.03), and at the end of the open-label extension period it was -6.34 kg for the Tesomet-Tesomet group and -6.03 kg for the placebo-Tesomet group. Mean change in waist circumference from baseline was -7.1 cm for the Tesomet group vs -1.2 cm for the placebo group at the end of the double-blind period, and -5.7 cm for the Tesomet-Tesomet group and -3.0 cm for the placebo-Tesomet group at the end of the open-label extension period. Most subjects (65%) had Levothyroxine reduced; adjustments in pituitary replacement and diabetic medications were otherwise few and did not differ significantly from baseline. Mean (SD) change in levothyroxine daily dose from baseline was -6.6% (6.1) and -6.4% (9.1) in Tesomet and placebo, respectively. In both groups, change in Levothyroxine correlated with weight-loss at time of adjustment (r2=0.37, P=0.006). This tendency was maintained during the extension period and implementing the reduction of levothyroxine in the management stabilised thyroid function.
Conclusion: Tesomet was generally well tolerated after 48 weeks of treatment, did not affect heart rate or blood pressure, and resulted in significant reductions in body weight in this cohort of hypopituitary patients with hypothalamic obesity. Weight-loss necessitated reductions in levothyroxine dose in most subjects to maintain stable thyroid function.
Volume 81
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Endocrine Abstracts
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