A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

Mirtazapine versus megestrol acetate in treatment of anorexia-cachexia in advanced cancer patients: a randomized, double-blind trial.

OBJECTIVE: Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients. METHODS: A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires. RESULTS: After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05). CONCLUSIONS: Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.

A randomised, double blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer.

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0-10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis.

AIMS: Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia. METHODS: PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI. RESULTS: 80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo. CONCLUSIONS: Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

Assessment of compounded transdermal mirtazapine as an appetite stimulant in cats with chronic kidney disease.

OBJECTIVES: The aim of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in cats with chronic kidney disease (CKD). METHODS: Two sequential double-blind placebo-controlled crossover prospective studies were performed in client-owned cats with stable stage 2 or 3 CKD and a history of decreased appetite. In the first study nine CKD cats were randomized to receive 3.75 mg/0.1 ml CTM gel or placebo on the inner pinna every other day for 3 weeks, then, after a 4 day washout period, the cats were crossed over to the alternate 3 week treatment. In a second study, 10 CKD cats were randomized to receive 1.88 mg/0.1 ml CTM or placebo on the same schedule. Physical examination and serum biochemistry were performed before and after each treatment period, and owners kept daily logs of appetite, activity and eating behaviors. Mirtazapine concentrations in CTM gels and steady-state mirtazapine serum concentrations were measured using liquid chromatography/tandem mass spectrometry. RESULTS: Administration of both 3.75 mg and 1.88 mg CTM resulted in a statistically significant increase in weight (P = 0.002 for both), increase in appetite (P = 0.01 and P = 0.005, respectively), and increase in rate of food consumption (P = 0.03 and P = 0.008, respectively). No significant difference in activity or vocalization was seen at either dose; however, individual cats experienced excessive meowing. Median weight increase for the 3.75 mg arm was 0.22 kg (range 0.04-0.44 kg), while median weight increase for the 1.88 mg arm was 0.26 kg (range -0.25 to 0.5 kg). Improvement in body condition score was seen in 5/9 cats in the 3.75 mg arm (P = 0.04) and 6/10 cats in the 1.88 mg arm (P = 0.004). CONCLUSIONS AND RELEVANCE: CTM increased appetite and resulted in weight gain in CKD cats despite significant inconsistencies in compounding, and may benefit cats in countries where an approved product is not available.

Fabrication of Eudragit polymeric nanoparticles using ultrasonic nebulization method for enhanced oral absorption of megestrol acetate.

Megestrol acetate (MGA) is used as a progestagen to treat advanced cancers in the breast or uterus and anorexia-cachexia syndrome in cancer patients. Due to its low solubility (BCS class II), MGA bioavailability needs to be enhanced for efficacy and safety. We developed MGA-encapsulated Eudragit® L100 (EUD) nanoparticles (MGA-EUD (1:1) and MGA-EUD (2:1)) using an ultrasonic nebulization method. MGA-EUD (1:1) and MGA-EUD (2:1) consisted of MGA and EUD at the mass ratios of 1:1 and 2:1. Their physicochemical properties, i.e. particle size, loading efficiency, morphology, and crystallinity were determined. Dissolution tests were performed using USP method II. For pharmacokinetics, they were orally administered at 50 mg/kg to mice. Microcrystalline MGA suspension (MGA-MC, Megace®, BMS) was used as control. MGA-EUD (1:1) and MGA-EUD (2:1) had a smooth and spherical shape of 0.70 and 1.05 µm in diameter with loading efficiencies of 93 and 95% showing amorphous states of MGA. They significantly enhanced the dissolution potential of MGA. Oral bioavailability of MGA-EUD (1:1) and MGA-EUD (2:1) increased 2.0- and 1.7-fold compared to that of MGA-MC. It suggests that ultrasonic nebulization method for the fabrication of polymeric nanoparticles is a promising approach to improve the bioavailability of poorly soluble drugs.

Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.

The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time course of BW loss, body composition, muscle mass, bone mineral density, and the cytokines interleukin-6 (IL-6) and macrophage-inhibitory cytokine-1 (MIC-1). Moreover, we measured the expression of the muscle degradation markers muscle RING-finger-protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx). After tumor inoculation, MIC-1 levels increased earlier than IL-6 and both cytokines were elevated before MuRF-1/MAFbx expression increased. Oral HM01 treatment increased BW, fat mass, and neuronal hypothalamic activity in healthy mice. In tumor-bearing mice, HM01 increased food intake, BW, fat mass, muscle mass, and bone mineral density while it decreased energy expenditure. These effects appeared to be independent of IL-6, MIC-1, MuRF-1 or MAFbx, which were not affected by HM01. Therefore, HM01 counteracts cachectic body weight loss under inflammatory conditions and is a promising compound for the treatment of cancer cachexia in the absence of severe anorexia.

The role of 5-HT2c receptor on corticosterone-mediated food intake.

Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice. Both corticosterone and mCPP increased c-Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c-Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5-HT2c receptors and leptin may be involved in the effects of corticosterone-induced hyperphagia.

A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9-tetrahydrocannabinol, elicits hyperphagia in rats.

Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour. Following a 2 h prefeed satiation procedure, 16 male Lister-hooded rats were administered CBG-BDS (at 30-240 mg/kg) or vehicle. Food intake, meal pattern microstructure and locomotor activity were recorded over 2 h. The total food intake was increased by 120 and 240 mg/kg CBG-BDS (1.53 and 1.36 g, respectively, vs. 0.56 g in vehicle-treated animals). Latency to feeding onset was dose dependently decreased at all doses, and 120 and 240 mg/kg doses increased both the number of meals consumed and the cumulative size of the first two meals. No significant effect was observed on ambulatory activity or rearing behaviour. CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of [INCREMENT]-tetrahydrocannabinol in the extract.

Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano-Crystallized Megestrol Acetate.

Megestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (PK) of the recently developed nano-crystallized megestrol acetate (NCMA), using a model-based approach. Data were obtained from an NCMA PK study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body-weight via allometry, NONMEM 7.3 was used to develop a PK model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (Cmax ) of NCMA close to those obtained with the fed dose. NCMA concentrations were best characterized by a two-compartment model with first-order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the PK model developed can be applied to an optimal dosage regimen design for NCMA treatment.

A novel role for xenopsin: Stimulation of food intake.

Xenopsin (XPN), an extract from frog skin, is comprised of 80 amino acids and exerts effects on the mammalian digestive tract. The purpose of the study presented here was to determine if XPN would affect food intake using chicks as models. Chicks which had been fasted for 180 min did not change food or water intake after central injection of XPN. However, ab libitum fed chicks which received 1 and 3 nmol central XPN increased food intake while water intake was not affected. When the dose was increased to 9 nmol chicks did not increase food intake but their water intake was reduced suggesting malaise. Chicks injected with XPN had increased c-Fos immunoreactivity in the lateral hypothalamus, but other hypothalamic appetite-associated nuclei were not affected. When XPN was directly injected into the lateral hypothalamus food intake was increased, suggesting a primary site of action. When the expression of appetite-associated neuropeptide mRNA was quantified chicks injected with XPN had increased proopiomelanocortin mRNA. Lastly, a comprehensive behavior analysis was performed and while XPN injected chicks had an increase in the number of feeding pecks, jumping, preening, deep rest and sitting were all decreased. Thus, we conclude that exogenous XPN functions as an orexigenic factor in chicks and its effects are mediated by the lateral hypothalamus.

Treatment of cachexia: An overview of recent developments.

Body wasting in the context of chronic illness is associated with reduced quality of life and impaired survival. Recent clinical trials have investigated different approaches to improve patients' skeletal muscle mass and strength, exercise capacity, and survival in the context of cachexia and body wasting, many of them in patients with cancer. The aim of this article is to summarise clinical trials published over the last two years. Therapeutic approaches discussed here include appetite stimulants like megestrol acetate, l-carnitine, or melatonin, anti-inflammatory drugs like thalidomide, pentoxyphylline, or a monoclonal antibody against interleukin-1α as well as ghrelin and the ghrelin agonist anamorelin, nutritional support, and anabolics like enobosarm and testosterone.

Tolerability and pharmacokinetics of two formulations of megestrol acetate under fed conditions in healthy volunteers.

PURPOSE: Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers. METHODS: This was a randomized, single-dose, 3-treatment, 3-period, 6-sequence, crossover study in healthy Korean volunteers. In each period, participants received single oral doses of conventional formulation 800 mg/20 mL (reference), nanocrystal dispersion 650 mg/5.2 mL (test 1), and nanocrystal dispersion 675 mg/5.4 mL (test 2) after a high-calorie, high-fat meal. The periods were separated by a washout period of 14 days. Serial blood samples were collected up to 120 hours after dosing. The plasma concentrations of megestrol acetate were determined with a validated LC-MS/MS method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability was assessed by physical examinations, vital signs, clinical laboratory test results, and electrocardiograms. FINDINGS: Thirty-eight healthy volunteers completed the study. The geometric mean ratios of the AUC(last) and C(max) for test 1/reference were 0.88 (90% CI, 0.84-0.92) and 1.07 (90% CI, 0.99-1.15), respectively. The geometric mean ratios of the AUC(last) and C(max) for test 2/reference were 0.88 (90% CI, 0.84-0.93) and1.03 (90% CI, 0.96-1.10), respectively. All formulations were well tolerated. IMPLICATIONS: The pharmacokinetic characteristics and tolerability of the 2 megestrol acetate formulations are similar in fed volunteers and suggest no relevant difference in tolerability. ClinicalTrials.gov identifier: NCT01342055.

Pharmacological appetite stimulation: rational choices in the inappetent cat.

PRACTICAL RELEVANCE: Inappetence is a commonly encountered problem in feline medicine. Primary goals in managing the inappetent or anorectic cat are to diagnose and treat the underlying disease and reinstate adequate nutrition. RATIONALE: As cats are intolerant of prolonged periods of inadequate nutritional intake, especially given their propensity to develop hepatic lipidosis, their increased requirements for amino acids, and inability to slow their rate of gluconeogenesis, symptomatic therapy and nutritional support is often required during diagnostic investigations. CLINICAL CHALLENGES: Most cats presenting with reduced food intake will be suffering from an underlying systemic disease, and so the mechanism of action, pharmacokinetics and contraindications of appetite-stimulating medications will need to be considered in each case to ensure rational use of these agents. Pharmacological appetite stimulation should never replace monitoring and ensuring adequate caloric intake, and may not be appropriate in some cases, such as critically ill or severely malnourished patients. EVIDENCE BASE: While there are no medications approved specifically for the treatment of anorexia in cats, some drugs have proven efficacious in the clinical field. Although several agents have been used historically for appetite stimulation, due to potential side effects and/or lack of efficacy or predictability only cyproheptadine and mirtazapine can currently be recommended for use.

Appetite stimulants for people with cystic fibrosis.

BACKGROUND: Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index and nutritional status. However, these may have adverse effects on clinical status. OBJECTIVES: The aim of this review is to systematically search for and evaluate evidence on the beneficial effects of appetite stimulants in the management of CF-related anorexia and synthesize reports of any side-effects. SEARCH METHODS: Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching reference lists and contacting local and international experts.Last search of online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials Register: 08 April 2014. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of appetite stimulants, compared to placebo or no treatment for at least one month in adults and children with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Authors independently extracted data and assessed the risk of bias within eligible trials. Meta-analyses were performed. MAIN RESULTS: Three trials (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine hydrochloride and megesterol acetate) to placebo were included; the numbers of adults or children within each trial were not always reported. The risk of bias of the included trials was graded as moderate.A meta-analysis of all three trials showed appetite stimulants produced a larger increase in weight z score at three months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to 0.93) (P < 0.001) (n = 40) with no evidence of a difference in effect between two different appetite stimulants. One of these trials also reported a significant weight increase with megesterol acetate compared to placebo at six months (n = 17). The three trials reported no significant differences in forced expiratory volume at one second (per cent predicted) between the appetite stimulant groups and placebo at follow up, with durations ranging from two to nine months. A meta-analysis of two trials showed a significantly higher proportion of patients reporting increased appetite, odds ratio 45.25 (95% confidence interval 3.57 to 573.33) (P = 0.003) (n = 23), but the frequency of reported side effects was undetermined. AUTHORS' CONCLUSIONS: In the short term (six months) in adults and children, appetite stimulants improved only two of the outcomes in this review - weight (or weight z score) and appetite; and side effects were insufficiently reported to determine the full extent of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon moderate quality data from a small number of trials and so this therapy cannot be conclusively recommended based upon the findings in the review. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any patients prescribed these medications accordingly.Research is needed to determine meaningful surrogate measures for appetite and define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.

Circulating glucagon-like peptide-1 (GLP-1) inhibits eating in male rats by acting in the hindbrain and without inducing avoidance.

To address the neural mediation of the eating-inhibitory effect of circulating glucagon-like peptide-1 (GLP-1), we investigated the effects of 1) intra-fourth ventricular infusion of the GLP-1 receptor antagonist exendin-9 or 2) area postrema lesion on the eating-inhibitory effect of intrameal hepatic portal vein (HPV) GLP-1 infusion in adult male rats. To evaluate the physiological relevance of the observed effect we examined 3) the influence of GLP-1 on flavor acceptance in a 2-bottle conditioned flavor avoidance test, and 4) measured active GLP-1 in the HPV and vena cava (VC) in relation to a meal and in the VC after HPV GLP-1 infusion. Intrameal HPV GLP-1 infusion (1 nmol/kg body weight-5 min) specifically reduced ongoing meal size by almost 40% (P < .05). Intra-fourth ventricular exendin-9 (10 µg/rat) itself did not affect eating, but attenuated (P < .05) the satiating effect of HPV GLP-1. Area postrema lesion also blocked (P < .05) the eating-inhibitory effect of HPV GLP-1. Pairing consumption of flavored saccharin solutions with HPV GLP-1 infusion did not alter flavor acceptance, indicating that HPV GLP-1 can inhibit eating without inducing malaise. A regular chow meal transiently increased (P < .05) HPV, but not VC, plasma active GLP-1 levels, whereas HPV GLP-1 infusion caused a transient supraphysiological increase (P < .01) in VC GLP-1 concentration 3 minutes after infusion onset. The results implicate hindbrain GLP-1 receptors and the area postrema in the eating-inhibitory effect of circulating GLP-1, but question the physiological relevance of the eating-inhibitory effect of iv infused GLP-1 under our conditions.