Efficacy, safety and tolerability of orlistat, a lipase inhibitor, in the treatment of adolescent weight excess

Bogarin, Roberto; Chanoine, Jean‐Pierre

doi:10.2217/14750708.6.1.23

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…Orlistat is generally well tolerated but it should be noted that prolonged use can cause side effects [23]–[26], [47], [49] and importantly, can interfere with the absorption of concomitantly orally administered lipophilic drugs [25]. For example, the case of a HIV patient was recently presented who showed reduced control of HIV infection under antiretroviral therapy in co-medication with orlistat presumably due to reduced uptake of Efavirenz, a lipophilic component of the anti-viral therapy [50].…”

Section: Discussionmentioning

confidence: 99%

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High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

et al. 2013

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Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC5024h = 2.8 µM) being more sensitive than WB-C6 (IC5024h = 6.2 µM). The effect was significantly more potent compared to MTZ (IC5024h = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis.

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Section: Discussionmentioning

confidence: 99%

“…It is widely used in humans for this purpose and thus can be considered relatively safe [23]–[26]. Recently, orlistat has been shown to inhibit the growth of pathogens, including apicomplexan parasites and trypanosomes, and that of cancer cells in vitro [18], [27]–[29].…”

Section: Introductionmentioning

confidence: 99%

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

et al. 2013

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“…A multivitamin is recommended with orlistat use due to increased risks of fat‐soluble vitamin and mineral deficiencies. Due to little cardiometabolic benefit, expense, and adverse tolerability in adolescents attending school where bathroom privileges may be limited, orlistat is not considered a first‐line drug for the treatment of pediatric obesity as monotherapy. Based on data from several human studies, treatment with orlistat for 1 year does not appear to affect pubertal development or the expected increase in lean body mass during puberty . Longer‐term studies are needed to understand the effects of orlistat on pubertal development.…”

Section: Recommendations (Table )mentioning

confidence: 99%

Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity

Srivastava

Fox

Kelly

et al. 2019

Obesity

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A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity‐related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration‐approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off‐label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.

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“…From Week 2 to Week 12 of this feeding schedule, the mice in the XEN group were treated orally with the anti-obesity drug Orlistat (Xenical ® , Roche, Milano, Italy; 10 mg/kg/day) as a positive control. This drug blocks the digestion of dietary triglycerides by inhibiting gastric and pancreatic lipases and is known to promote weight loss and improve obesity-related risk factors in obese subjects with and without metabolic complications [33]. The animals in the PR and fPR groups were exposed to PR (400 mg/kg/day) or fPR (400 mg/kg/day), respectively.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Lactate-Fortified Puerariae Radix Fermented by Bifidobacterium breve Improved Diet-Induced Metabolic Dysregulation via Alteration of Gut Microbial Communities

Choi

Bose²,

Shin

et al. 2020

Nutrients

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Background: Puerariae Radix (PR), the dried root of Pueraria lobata, is reported to possess therapeutic efficacies against various diseases including obesity, diabetes, and hypertension. Fermentation-driven bioactivation of herbal medicines can result in improved therapeutic potencies and efficacies. Methods: C57BL/6J mice were fed a high-fat diet and fructose in water with PR (400 mg/kg) or PR fermented by Bifidobacterium breve (400 mg/kg) for 10 weeks. Histological staining, qPCR, Western blot, and 16s rRNA sequencing were used to determine the protective effects of PR and fermented PR (fPR) against metabolic dysfunction. Results: Treatment with both PR and fPR for 10 weeks resulted in a reduction in body weight gain with a more significant reduction in the latter group. Lactate, important for energy metabolism and homeostasis, was increased during fermentation. Both PR and fPR caused significant down-regulation of the intestinal expression of the MCP-1, IL-6, and TNF-α genes. However, for the IL-6 and TNF-α gene expressions, the inhibitory effect of fPR was more pronounced (p < 0.01) than that of PR (p < 0.05). Oral glucose tolerance test results showed that both PR and fPR treatments improved glucose homeostasis. In addition, there was a significant reduction in the expression of hepatic gene PPARγ, a key regulator of lipid and glucose metabolism, following fPR but not PR treatment. Activation of hepatic AMPK phosphorylation was significantly enhanced by both PR and fPR treatment. In addition, both PR and fPR reduced adipocyte size in highly significant manners (p < 0.001). Treatment by fPR but not PR significantly reduced the expression of PPARγ and low-density lipoproteins in adipose tissue. Conclusion: Treatment with fPR appears to be more potent than that of PR in improving the pathways related to glucose and lipid metabolism in high-fat diet (HFD)+fructose-fed animals. The results revealed that the process of fermentation of PR enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities.

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Efficacy, safety and tolerability of orlistat, a lipase inhibitor, in the treatment of adolescent weight excess

Cited by 8 publications

References 45 publications

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity

Lactate-Fortified Puerariae Radix Fermented by Bifidobacterium breve Improved Diet-Induced Metabolic Dysregulation via Alteration of Gut Microbial Communities

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