Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes.
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).


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.
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands js.tenkulve@vumc.nl.
Jennifer S
JS
Ten Kulve
Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Dick J
DJ
Veltman
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Liselotte
L
van Bloemendaal
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Frederik
F
Barkhof
Endocrine Section, Department of Internal Medicine, VU University Medical Center, and the Department of Clinical Neuropsychology, VU University, Amsterdam, the Netherlands.
Madeleine L
ML
Drent
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Michaela
M
Diamant
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Richard G
RG
IJzerman
D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003463:Cues; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D005502:Food; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000627:therapeutic use; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012527:Satiation / Q000187:drug effects*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1