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Objectives: Antimicrobial stewardship (AMS) teams around the world include pharmacists; however, their impact is relatively unknown. This study aimed to explore the relationship between pharmacists’ actions and antibiotic consumption. Methods: Hospital pharmacists involved in the French antibiotic consumption surveillance network (ATB-Raisin) were invited to participate in a retrospective observational multicentre study. Collected data were: the previous year’s (2016) antibiotic consumption expressed in daily defined dose per 1000 patient-days; AMS measures, including pharmacist-specific actions; and use of a computerised prescription order entry (CPOE) system. Associations between antibiotic consumption and AMS measures were assessed by linear regression, after adjustment for hospital activities. Results: Annual data for 2016 from 77 hospitals (7 260 000 bed-days in 24 000 beds) were analysed. Pharmacists were involved in AMS programs in 73% of hospitals, and were the antibiotic advisor in 25%. Pharmaceutical review of prescriptions was organised in almost all hospitals (97%). The univariable analysis identified five measures associated with lower overall antibiotic consumption: CPOE use (if >80% of prescriptions or 100%), pharmaceutical review (if >80% of beds or 100%) and the antibiotic advisor being a pharmacist (P = 0.04, P = 0.004 and P = 0.003, respectively). In the multivariable analysis, two explanatory variables were significantly and independently associated with a lower overall antibiotic consumption: the antibiotic advisor being a pharmacist and a pharmaceutical review covering all beds (–19.9% [–31.6%; –8.1%], P = 0.002 and –18.3% [–34.0%; –2.6%], P = 0.03, respectively). Conclusions: Antibiotic consumption was lower when the antibiotic advisor was a pharmacist and when the pharmaceutical team reviewed all prescriptions. These results highlight that actions initiated by pharmacists have a positive impact and should be supported.

Abstract Background Sedative-hypnotics (SHs) are widely used in France but there are no available data addressing their prescription specifically in hospitalized older patients. The objective is thus to determine the cumulative incidence of sedative-hypnotic (SH) medications initialized during a hospital stay of older patients, the proportion of SH renewal at discharge among these patients and to study associated risk factors. Methods We conducted a retrospective observational study in six internal medicine units and six acute geriatric units in eight hospitals (France). We included 1194 inpatients aged 65 and older without SH medications prior to hospitalization. Data were obtained from patients’ electronic pharmaceutical records. Primary outcome was the cumulative incidence of SH initiation in the study units. Secondary outcomes were the proportion of SH renewal at discharge and risk factors for SH initiation and renewal at discharge (patient characteristics, hospital organization). A Cox regression model was used to study risk factors for SH initiation. A mixed effects logistic regression was used to study risk factors for SH renewal at discharge. Results SH initiation occurred in 21.5% of participants 20 days after admission. SH renewal at discharge occurred in 38.7% of patients who had initiated it during their stay and were discharged home and in 56.0% of patients discharged to rehabilitation facilities. Neither patients’ characteristics nor hospital organization patterns was associated with SH initiation. SH initiation after the first six days after admission was associated with a lower risk of SH renewal in patients discharged to rehabilitation facilities (OR = 0.19, 95% CI: [0.04–0.80]). Conclusions Hospitalization is a period at risk for SH initiation. The implementation of interventions promoting good use of SHs is thus of first importance in hospitals. Specific attention should be paid to patients discharged to rehabilitation facilities.

Objectives The aim of this systematic review was to describe and analyse the performance statistics of validated risk scores identifying elderly inpatients at risk of early unplanned readmission.Data sources We identified potentially eligible studies by searching MEDLINE, EMBASE, COCHRANE and Web of Science. Our search was restricted to original studies, between 1966 and 2018.Eligibility criteria Original studies, which internally or externally validated the clinical scores of hospital readmissions in elderly inpatients.Data extraction and synthesis A data extraction grid based on Strengthening the Reporting of Observational Studies in Epidemiology and Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statements was developed and completed by two reviewers to collect general data. The same process was used to extract metrological data of the selected scores.Quality assessment of the included studies Assessment of the quality and risk of bias in individual studies was performed by two reviewers, using the validated Effective Public Health Practice Project quality assessment tool.Participants Elderly inpatients discharged to home from hospital or returning home after an accident and emergency department visit.Results A total of 12 studies and five different scores were included in the review. The five scores present area under the receiving operating characteristic curve between 0.445 and 0.69. Identification of Senior At Risk (ISAR) and Triage Risk Screening Tool (TRST) scores were the more frequently validated scores with ISAR being more sensitive and TRST more specific.Conclusions The TRST and ISAR scores have been extensively studied and validated. The choice of the most suitable score relies on available patient data, patient characteristics and the foreseen clinical care intervention. In order to pair the intervention with the appropriate clinical score, further studies of external validation of clinical scores, identifying elderly patients at risk of early unplanned readmission, are needed.PROSPERO registration number CRD42017054516.

The burden of Sedative-Hypnotics (SHs) has been known since the 1980s. Yet, their consumption remains high. A systematic review of the literature should help to assess efficient interventions to improve the appropriate use of SHs in sleep disorders.To identify and assess regulatory and educational interventions designed to improve the appropriate use of SHs for insomnia treatment.We conducted a systematic review of the literature according to PRISMA guidelines. A systematic search covering the period 1980-2015 was carried out in Medline, Web of Science, Embase and PsycInfo. We included studies reporting the implementation of regulatory or educational strategies directed towards patients and/or healthcare professionals to improve the appropriate use of SHs to treat insomnia in the community, hospitals and nursing homes.Thirty-one studies were included: 23 assessed educational interventions (recommendations by mail/email, computer alerts, meetings, mass media campaigns, prescription profile), 8 assessed regulatory interventions (prescription rule restriction, end of reimbursement). The most recent was implemented in 2009. Restrictive prescription rules were effective to reduce the consumption of targeted SHs but led to a switch to other non-recommended SHs. Among educational interventions, only 3 studies out of 7 reported positive results of mono-faceted interventions; whereas, 13 out of the 16 multi-faceted interventions were reported as efficient: particularly, the active involvement of healthcare professionals and patients and the spread of information through mass media were successful. The risk of bias was high for 24 studies (mainly due to the design), moderate for 3 studies and weak for 4 studies.Educational multifaceted studies are presented as the most efficient. But further better designed studies are needed to make evidence-based results more generalizable.

To assess the impact of the implementation of a Computerized Physician Order Entry (CPOE) associated with a pharmaceutical checking of medication orders on medication errors in the 3 stages of drug management (i.e. prescription, dispensing and administration) in an orthopaedic surgery unit.A before-after observational study was conducted in the 66-bed orthopaedic surgery unit of a teaching hospital (700 beds) in Paris France. Direct disguised observation was used to detect errors in prescription, dispensing and administration of drugs, before and after the introduction of computerized prescriptions. Compliance between dispensing and administration on the one hand and the medical prescription on the other hand was studied. The frequencies and types of errors in prescribing, dispensing and administration were investigated.During the pre and post-CPOE period (two days for each period) 111 and 86 patients were observed, respectively, with corresponding 1,593 and 1,388 prescribed drugs. The use of electronic prescribing led to a significant 92% decrease in prescribing errors (479/1593 prescribed drugs (30.1%) vs 33/1388 (2.4%), p < 0.0001) and to a 17.5% significant decrease in administration errors (209/1222 opportunities (17.1%) vs 200/1413 (14.2%), p < 0.05). No significant difference was found in regards to dispensing errors (430/1219 opportunities (35.3%) vs 449/1407 (31.9%), p = 0.07).The use of CPOE and a pharmacist checking medication orders in an orthopaedic surgery unit reduced the incidence of medication errors in the prescribing and administration stages. The study results suggest that CPOE is a convenient system for improving the quality and safety of drug management.

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Objective: To collect the community pharmacists' perception on their role in the medication reconciliation's process., Methods: We did an observational transverse study thanks to a survey of community pharmacists working in France, conducted in 2020. A digital questionnaire was submitted to Parisian community pharmacists before being shared on two Facebook groups. The responses were analysed with Microsoft Excel® software. We calculated percentages, used Chi 2  or Fisher's exact tests and did qualitative analyses., Results: We collected the perception of 135 community pharmacists, the majority was women (80%), relatively young (69.6% of 40 years old or less). They were 63.7% to claim knowing the medication reconciliation, but they could not define it properly. The subject's knowledge was statistically related to age (P-value<0.001) and previous contacts of the health care facilities (P-value<0.001). The majority of interviewed pharmacist considered the transmission of information to those health facilities as relevant and feasible and they expressed their willingness to get involved. However, they were limited by some obstacles such as the non-exhaustiveness of the medicinal record, the unsecured mail and the lack of feedbacks., Conclusions: Although the community pharmacists expressed interest for the medication reconciliation process and willingness to get involved, their role remained limited. Therefore, this process needs an improvement of its organisation and a generalisation of its practice to really benefit the hospital-community transition's safety., (Copyright © 2023 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To describe older patients hospitalized for falls, at risk of readmission and priority for interventions to reduce this risk., Methods: We conducted an observational, monocentric, prospective study (from April to June 2019). The inclusion criteria were: patients aged 75 and over, admitted to the Emergency Department for falls, consenting to the study. For patients subsequently hospitalized, the geriatric scores were determined (risk of readmission [ISAR score], state of frailty, degree of autonomy [Katz score]), and when appropriate, medication treatments were listed and compliance of patients was assessed (Girerd score)., Results: In three months, 154 patients were included (median age 86 years [min 75-max 103], sex ratio 0.44), of which 73 patients were hospitalized. Among these patients, 63% presented a high risk of readmission; 45.2% are likely to become frail; 72.6% were dependent. Finally, 53 of the 73 patients (72.6%) had a treatment in primary care and presented a 71.7% non-compliance or low-compliance rate. Fifty height patients (79.5%) had at least 1 drug associated with fall [min 1-max 7]., Conclusions: Older patients presenting at hospital with a fall were numerous, often likely to become frail and dependent for the majority of them. As the readmission risk is also very high in this population, future studies aiming at reducing the risk of hospital readmission are needed., (Copyright © 2020 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Falls are an important issue in older adults as they are frequent, deleterious, and often lead to repeated consultations at the emergency department (ED) and unplanned hospitalizations. Our principal objective was to provide an inventory of interventions designed to prevent unplanned readmissions or ED visits of older patients presenting to hospital with a fall., Design: Systematic review performed on February 11, 2019 in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science, without date or language restriction. We manually updated this search in August 1, 2019. Study selection, data extraction and risk of bias assessment were conducted independently by 2 reviewers., Setting and Participants: We included studies reporting interventions to prevent unplanned readmissions or ED visits of older patients (aged 65 years or over) presenting to hospital because of a fall., Results: We identified 475 unique citations after removing duplicates and included 6 studies (2 observational and 4 interventional studies). The studies were published between 2012 and 2019; they evaluated heterogeneous interventions that were frequently multifaceted and multidisciplinary. The interventions were shown effective in reducing readmissions or ED revisits compared with control groups in 3 studies (relative risk reductions between 30% and 65%), all of which were multifaceted and 2/3 multidisciplinary., Conclusions and Implications: With 6 articles showing inconsistent results, our study highlights the need to adequately design and evaluate interventions to reduce the burden of hospital readmissions among older fallers. Retrieved studies are recent, which underlines that hospital readmissions are a current concern for researchers and public health authorities [PROSPERO registration number: CRD42019131965]., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this systematic review was to describe and analyse the performance statistics of validated risk scores identifying elderly inpatients at risk of early unplanned readmission., Data Sources: We identified potentially eligible studies by searching MEDLINE, EMBASE, COCHRANE and Web of Science. Our search was restricted to original studies, between 1966 and 2018., Eligibility Criteria: Original studies, which internally or externally validated the clinical scores of hospital readmissions in elderly inpatients., Data Extraction and Synthesis: A data extraction grid based on Strengthening the Reporting of Observational Studies in Epidemiology and Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statements was developed and completed by two reviewers to collect general data. The same process was used to extract metrological data of the selected scores., Quality Assessment of the Included Studies: Assessment of the quality and risk of bias in individual studies was performed by two reviewers, using the validated Effective Public Health Practice Project quality assessment tool., Participants: Elderly inpatients discharged to home from hospital or returning home after an accident and emergency department visit., Results: A total of 12 studies and five different scores were included in the review. The five scores present area under the receiving operating characteristic curve between 0.445 and 0.69. Identification of Senior At Risk (ISAR) and Triage  Risk Screening Tool (TRST) scores were the more frequently validated scores with ISAR being more sensitive and TRST more specific., Conclusions: The TRST and ISAR scores have been extensively studied and validated. The choice of the most suitable score relies on available patient data, patient characteristics and the foreseen clinical care intervention. In order to pair the intervention with the appropriate clinical score, further studies of external validation of clinical scores, identifying elderly patients at risk of early unplanned readmission, are needed., Prospero Registration Number: CRD42017054516., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Many recent randomized controlled trials in the field of septic shock failed to demonstrate a benefit on mortality. Randomized controlled trials increasingly report organ support duration and organ support-free days as primary or secondary outcomes. We conducted a methodologic systematic review to assess how organ support outcomes were defined and reported in septic shock randomized controlled trials., Data Sources: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science., Study Selection: We included randomized controlled trials published between January 2004 and March 2018 that involved septic shock adults and assessed organ support duration and/or organ support-free days for hemodynamic support, respiratory support, or renal replacement therapy., Data Extraction: For each randomized controlled trial, we extracted the definitions of organ support duration and organ support-free days. We particularly evaluated how nonsurvivors were accounted for. Study authors were contacted to provide any missing information regarding these definitions., Data Synthesis: We included 28 randomized controlled trials. Organ support duration and organ support-free days outcomes were reported in 17 and 15 randomized controlled trials, respectively, for hemodynamic support, 15 and 15 for respiratory support, and five and nine for renal replacement therapy. Nonsurvivors were included in the organ support duration calculation in 13 of 14 randomized controlled trials (93%) for hemodynamic support and nine of 10 (90%) for respiratory support. The organ support-free days definition for hemodynamic support, respiratory support, and renal replacement therapy was reported in six of 15 randomized controlled trials (40%), eight of 15 randomized controlled trials (53%), and six of nine randomized controlled trials (67%) reporting an organ support-free days outcome, respectively. Of these, one half assigned "0" to nonsurvivors, and the other half attributed one point per day alive free of organ support up to a predefined time point., Conclusions: This study highlights the heterogeneity and infrequency of organ support duration/organ support-free days outcome reporting in septic shock trials. When reported, the definitions of these outcome measures and methods of calculation are also infrequently reported, in particular how nonsurvivors were accounted for, which may have an important impact on interpretation.

Background: Sedative-hypnotics (SHs) are widely used in France but there are no available data addressing their prescription specifically in hospitalized older patients. The objective is thus to determine the cumulative incidence of sedative-hypnotic (SH) medications initialized during a hospital stay of older patients, the proportion of SH renewal at discharge among these patients and to study associated risk factors., Methods: We conducted a retrospective observational study in six internal medicine units and six acute geriatric units in eight hospitals (France). We included 1194 inpatients aged 65 and older without SH medications prior to hospitalization. Data were obtained from patients' electronic pharmaceutical records. Primary outcome was the cumulative incidence of SH initiation in the study units. Secondary outcomes were the proportion of SH renewal at discharge and risk factors for SH initiation and renewal at discharge (patient characteristics, hospital organization). A Cox regression model was used to study risk factors for SH initiation. A mixed effects logistic regression was used to study risk factors for SH renewal at discharge., Results: SH initiation occurred in 21.5% of participants 20 days after admission. SH renewal at discharge occurred in 38.7% of patients who had initiated it during their stay and were discharged home and in 56.0% of patients discharged to rehabilitation facilities. Neither patients' characteristics nor hospital organization patterns was associated with SH initiation. SH initiation after the first six days after admission was associated with a lower risk of SH renewal in patients discharged to rehabilitation facilities (OR = 0.19, 95% CI: [0.04-0.80])., Conclusions: Hospitalization is a period at risk for SH initiation. The implementation of interventions promoting good use of SHs is thus of first importance in hospitals. Specific attention should be paid to patients discharged to rehabilitation facilities.

Background: The burden of Sedative-Hypnotics (SHs) has been known since the 1980s. Yet, their consumption remains high. A systematic review of the literature should help to assess efficient interventions to improve the appropriate use of SHs in sleep disorders., Objectives: To identify and assess regulatory and educational interventions designed to improve the appropriate use of SHs for insomnia treatment., Methods: We conducted a systematic review of the literature according to PRISMA guidelines. A systematic search covering the period 1980-2015 was carried out in Medline, Web of Science, Embase and PsycInfo. We included studies reporting the implementation of regulatory or educational strategies directed towards patients and/or healthcare professionals to improve the appropriate use of SHs to treat insomnia in the community, hospitals and nursing homes., Results: Thirty-one studies were included: 23 assessed educational interventions (recommendations by mail/email, computer alerts, meetings, mass media campaigns, prescription profile), 8 assessed regulatory interventions (prescription rule restriction, end of reimbursement). The most recent was implemented in 2009. Restrictive prescription rules were effective to reduce the consumption of targeted SHs but led to a switch to other non-recommended SHs. Among educational interventions, only 3 studies out of 7 reported positive results of mono-faceted interventions; whereas, 13 out of the 16 multi-faceted interventions were reported as efficient: particularly, the active involvement of healthcare professionals and patients and the spread of information through mass media were successful. The risk of bias was high for 24 studies (mainly due to the design), moderate for 3 studies and weak for 4 studies., Conclusion: Educational multifaceted studies are presented as the most efficient. But further better designed studies are needed to make evidence-based results more generalizable.

Objectives: To determine whether potentially inappropriate medications (PIMs) or potentially inappropriate associations (PIAs) prescribed knowingly are associated with patient monitoring., Design: Prospective observational study., Setting: Geriatric units (n = 56) in 28 hospitals., Participants: Inpatients aged 75 and older (N = 1,327)., Measurements: Potentially inappropriate prescriptions (PIP) were defined as a PIM or a PIA selected by an expert board from lists of explicit criteria (Beers, Priscus, Laroche, French Health Agency) using a Delphi process. They were considered to be prescribed knowingly if they were maintained after reassessment by the geriatrician and the clinical pharmacist. Primary outcome was the rate of PIPs maintained (prescribed knowingly) and for which a geriatrician declared that specific monitoring was performed. Secondary outcomes were the parameters monitored and the rate of participants receiving knowingly a PIP., Results: One thousand sixty-three PIPs were detected in 607 participants (46%). After reassessment, 826 (78%) PIPs were maintained in 490 participants (37%), the main reasons being participant's regular treatment and lack of alternative. Psychotropic (36%), cardiovascular (including antithrombotics) (29%), and laxative or antiemetic drugs (16%) were the most-frequent classes prescribed knowingly. The geriatricians declared to perform clinical or biological monitoring for 69% (n = 570) of PIMs or PIAs prescribed knowingly. Three types of specific monitoring were identified: clinical, biological, and follow-up with a specialist., Conclusion: Approximately three-quarters of PIMs or PIAs were prescribed knowingly, of which 69% were monitored, with wide variations in occurrence and in quality according to drug classes. This underlines the need for accurate guidelines on PIP monitoring., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Aim: To assess the impact of the implementation of a Computerized Physician Order Entry (CPOE) associated with a pharmaceutical checking of medication orders on medication errors in the 3 stages of drug management (i.e. prescription, dispensing and administration) in an orthopaedic surgery unit., Methods: A before-after observational study was conducted in the 66-bed orthopaedic surgery unit of a teaching hospital (700 beds) in Paris France. Direct disguised observation was used to detect errors in prescription, dispensing and administration of drugs, before and after the introduction of computerized prescriptions. Compliance between dispensing and administration on the one hand and the medical prescription on the other hand was studied. The frequencies and types of errors in prescribing, dispensing and administration were investigated., Results: During the pre and post-CPOE period (two days for each period) 111 and 86 patients were observed, respectively, with corresponding 1,593 and 1,388 prescribed drugs. The use of electronic prescribing led to a significant 92% decrease in prescribing errors (479/1593 prescribed drugs (30.1%) vs 33/1388 (2.4%), p < 0.0001) and to a 17.5% significant decrease in administration errors (209/1222 opportunities (17.1%) vs 200/1413 (14.2%), p < 0.05). No significant difference was found in regards to dispensing errors (430/1219 opportunities (35.3%) vs 449/1407 (31.9%), p = 0.07)., Conclusion: The use of CPOE and a pharmacist checking medication orders in an orthopaedic surgery unit reduced the incidence of medication errors in the prescribing and administration stages. The study results suggest that CPOE is a convenient system for improving the quality and safety of drug management.

Adverse drug events (ADE) may lead to hospital admission, and in some cases admission to an ICU is mandatory. We conducted a systematic review dealing with the incidence of ADE requiring ICU admission in adult patients, the reference population being all ICU admissions. Medline, Embase and Web of Science databases were screened from January 1982 to July 2014, using appropriate key words. Only original articles in English reporting the incidence of ADE requiring ICU admission in adult patients among total ICU admissions were included. Article eligibility was assessed by two independent reviewers, a third being involved in cases of disagreement. All reported characteristics (type of ICU, characteristics of patients, incidence of ADE, severity and preventability, drugs involved, causality) in the selected articles were collected for the review. The quality of studies was independently assessed by two reviewers with a specific score that we developed. A meta-analysis was conducted. Inclusion criteria were fulfilled by 11 studies out of the 4,311 identified in the initial literature search. The median (interquartile) quality score was 0.61 (0.44; 0.69). The reported incidences of ADE requiring ICU admission in adult patients ranged from 0.37 to 27.4%, with an associated mortality rate ranging from 2 to 28.1% and a mean length of stay ranging from 2.3 to 6.4 days. Preventable events accounted for 17.5 to 85.7% of the events. Costs and mechanisms at the root of ADE were investigated in only two and five studies, respectively. The forest plot examining the incidence of ADE requiring ICU admission in adult patients was associated with high heterogeneity (I (2) statistic > 98%), and the shape of the corresponding funnel plot was asymmetric. Heterogeneity across studies concerned many features, including studied populations, events considered, causality assessment methods, definitions of preventability and severity. Despite the heterogeneity of the reports, our review indicates that ICU admission due to ADE is a significant issue that should deserve further interest. The review led us to propose a list of items devoted to the reporting of future studies on ADE requiring ICU admissions.

The oligopeptide transporter peptide cotransporter-1 Slc15a1 (PEPT1) plays a major role in the regulation of nitrogen supply, since it is responsible for 70% of the dietary nitrogen absorption. Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters (Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (+40%) and an increased intestinal permeability (+80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue.

Leptin is a major determinant of energy homeostasis, acting both centrally and in the gastrointestinal tract. We previously reported that acute leptin treatment enhances the absorption of di- and tripeptides via the proton-dependent PepT1 transporter. In this study, we investigated the long term effect of leptin on PepT1 levels and activity in Caco2 cell monolayers in vitro. We then assessed the significance of the regulation of PepT1 in vivo in a model of diet-induced obesity. We demonstrated that 1) leptin regulated PepT1 at the transcriptional level, via the MAPK pathway, and at the translational level, via ribosomal protein S6 activation, in Caco2 cells and 2) this activation was systematically followed by a time- and concentration-dependent loss of leptin action reflecting desensitization. Deciphering this desensitization, we demonstrated that leptin induced a down-regulation of its own receptor protein and mRNA expression. More importantly, we showed, in mice with diet-induced obesity, that a 4-week hypercaloric diet resulted in a 46% decrease in PepT1-specific transport, because of a 30% decrease in PepT1 protein and a 50% decrease in PepT1 mRNA levels. As shown in Caco2 cells, these changes in PepT1 were supported by a parallel 2-fold decrease in leptin receptor expression in mice. Taken together, these results indicate that during induction of obesity, leptin resistance may also occur peripherally in the gastrointestinal tract, disrupting the absorption of oligopeptides and peptidomimetic drugs.