Liraglutide as a Potentially Useful Agent for Regulating Appetite in Diabetic Patients with Hypothalamic Hyperphagia and Obesity

Ando, Takao; Haraguchi, Ai; Matsunaga, Tomoe; Natsuda, Shoko; Yamasaki, Hironori; Usa, Toshiro; Kawakami, Atsushi

doi:10.2169/internalmedicine.53.1646

Cited by 24 publications

(17 citation statements)

References 31 publications

(32 reference statements)

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“…In the current study, obese animals showed glucose intolerance/insulin resistance, resistance to anorexigenic effect of leptin, elevated Bax/Bcl2 ratio, and microgliosis, indicating inflammation with stimulation of the pro-apoptosis in the ARC nucleus. We observed that liraglutide led to BM loss and carbohydrate metabolism improvement, confirming previous studies (1). The liraglutide treatment resulted in a leptin sensitivity enhancement, with reduction of microgliosis and stimulation of Bcl2, thus reducing the Bax/Bcl2 ratio.…”

Section: Discussionsupporting

confidence: 91%

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

Barreto-Vianna

Águila

Mandarim-de-Lacerda

2016

Obesity

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Objective: The neuroprotective effects of liraglutide (200 lg/kg, twice daily, subcutaneous administration) in the hypothalamic arcuate nucleus (ARC) of diet-induced obese mice were investigated. Methods: C57BL/6 mice were separated into groups: standard chow treated with vehicle or liraglutide and the respective liraglutide pair-fed group; high-fat diet treated with vehicle or liraglutide and the respective pair-fed group. Body mass (BM) evolution, carbohydrate metabolism, leptin resistance, proteins involved in energetic balance, apoptosis, and microglia in the ARC were studied. Results: Obese animals showed glucose intolerance, resistance to insulin and to anorexigenic effect of leptin, and microgliosis accompanied by elevated Bax/Bcl2 ratio in the ARC. Liraglutide improved the carbohydrate metabolism, BM loss, and the activation of pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) in the ARC. The liraglutide enhanced leptin sensitivity and diminished the microgliosis with decrease in Bax/Bcl2 ratio. Conclusions: Liraglutide activates central anorexigenic pathways, thereby diminishing the energy intake of obese mice and improving the metabolic parameters related to obesity. Liraglutide is a relevant neuroprotective agent, which can decrease the microgliosis and stimulate the anti-apoptotic pathway, a significant effect in the treatment of obesity and its comorbidities. Some benefits of liraglutide are independent of the BM loss, which usually accompanies the drug administration.

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Section: Discussionsupporting

confidence: 91%

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

Barreto-Vianna

Águila

Mandarim-de-Lacerda

2016

Obesity

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“…While weight loss was small, untreated patients continued to gain weight and our measured weight change may be an underestimation. Previous case reports showed greater than expected weight loss of 12.6 ± 7.1 kg in 11 patients with HO treated with GLP1RAs for ≥6 months . All but one patient had T2D, while our participants were treated for obesity.…”

Section: Discussionmentioning

confidence: 44%

“…GLP1RA may also increase energy expenditure . There are case reports of successful weight loss after treatment with GLP1RAs in patients with HO but no prospective pilot studies . The goal of this clinical trial was to investigate changes in body weight before and during treatment with exenatide.…”

Section: Introductionmentioning

confidence: 99%

A 52‐week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity

Lomenick

Buchowski

Shoemaker

2016

Obesity

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Background/Objectives Hypothalamic obesity (HO) is a common complication of hypothalamic tumors and effective therapies are lacking. The objective of this pilot study was to investigate changes in body weight before and during treatment with exenatide. Subjects/Methods This was a prospective, open-label 52-week pilot study of exenatide (10 mcg b.i.d.) in adults with HO. Ten patients enrolled and 8 completed the study. Study measures included indirect calorimetry, body composition, buffet meals, diet recall, actigraphy and hormone assays. Results Participants were obese with a baseline weight of 137.2 ± 37.6 kg. Exenatide therapy was well tolerated. Change in weight with exenatide therapy was not significant (−1.4 ± 4.3 kg [95% CI −2.2 to 4.9], p=0.40) but 6 of 8 completers lost weight (−6.2 to −0.2 kg). Participants reported significantly lower intake on food recall during treatment compared with baseline (7837.8 ± 2796.6 vs. 6258.4 ± 1970.7 kJ [95% CI −2915.8 to −242.6], p= 0.027) but there was no change in intake during buffet meals. Conclusions We did not observe significant weight loss in patients with HO treated with exenatide but 75% of completers had stable or decreasing weight. Further studies are needed to evaluate weight loss efficacy in patients with HO.

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“…In addition, liraglutide has beneficial effects on waist circumference and numerous metabolic parameters including inflammatory markers, blood pressure (BP) and plasma lipids [3], thus improving the cardio-metabolic profile of patients with T2DM [4, 5]. Similar beneficial effects of liraglutide on metabolic parameters were also seen in obese individuals with prediabetes who were at high risk for progression to T2DM and the development of cardiovascular disease (CVD) [6], as well as in subjects who had hypothalamic pituitary injury followed by hyperphagia, in whom several features of the metabolic syndrome (MetS) were present [7]. …”

Section: Introductionmentioning

confidence: 99%

Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study

Rizzo

Rizvi

Patti

et al. 2016

Cardiovasc Diabetol

115

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BackgroundLiraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM.MethodsWe performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subjects (71 men and 50 women; mean age: 62 ± 9 years) with T2DM and the MetS, who were naïve to incretin-based therapies and treated with metformin only, were included. Liraglutide (1.2 mg/day) was added to metformin (1500–3000 mg/day) for the entire study. Fasting plasma samples for metabolic parameters were collected and carotid-intima media thickness (cIMT) was assessed by B-mode real-time ultrasound at baseline and every 6 months thereafter.ResultsThere was a significant reduction in waist circumference, body mass index, fasting glycemia, HbA1c, total- and LDL-cholesterol, triglycerides, and cIMT during the 18-month follow-up. Correlation analysis showed a significant association between changes in cIMT and triglycerides (r = 0.362; p < 0.0001). The MetS prevalence significantly reduced during the study, and the 26% of subjects no longer fulfilled the criteria for the MetS after 18 months.ConclusionsLiraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study. Trial Registration ClinicalTrials.gov: NCT01715428.

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Liraglutide as a Potentially Useful Agent for Regulating Appetite in Diabetic Patients with Hypothalamic Hyperphagia and Obesity

Cited by 24 publications

References 31 publications

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

A 52‐week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity

Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study

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