Jennifer S Ten Kulve1, Dick J Veltman2, Liselotte van Bloemendaal3, Frederik Barkhof4, Madeleine L Drent5, Michaela Diamant3, Richard G IJzerman3. 1. Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands js.tenkulve@vumc.nl. 2. Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands. 3. Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands. 4. Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. 5. Endocrine Section, Department of Internal Medicine, VU University Medical Center, and the Department of Clinical Neuropsychology, VU University, Amsterdam, the Netherlands.
Abstract
OBJECTIVE:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS). RESEARCH DESIGN AND METHODS: We performed a randomized crossover study in obese patients with type 2 diabetes (n = 20, mean age 59.3 ±4.1 years, mean BMI 32 ± 4.7 kg/m(2)), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulin glargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake. RESULTS: After 12 weeks, the decrease in HbA1c was larger with liraglutide versus insulin glargine (Δ-0.7% vs. -0.2%, P < 0.001). Body weight decreased during liraglutide versus insulin glargine (Δ-3.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulin glargine, showed decreased responses to food pictures in insula and putamen (P ≤ 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P ≤ 0.05). Differences between liraglutide and insulin glargine were not observed after 12 weeks. CONCLUSIONS: Compared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment.
RCT Entities:
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS). RESEARCH DESIGN AND METHODS: We performed a randomized crossover study in obesepatients with type 2 diabetes (n = 20, mean age 59.3 ± 4.1 years, mean BMI 32 ± 4.7 kg/m(2)), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulinglargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake. RESULTS: After 12 weeks, the decrease in HbA1c was larger with liraglutide versus insulinglargine (Δ-0.7% vs. -0.2%, P < 0.001). Body weight decreased during liraglutide versus insulinglargine (Δ-3.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulinglargine, showed decreased responses to food pictures in insula and putamen (P ≤ 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P ≤ 0.05). Differences between liraglutide and insulinglargine were not observed after 12 weeks. CONCLUSIONS: Compared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment.
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