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The Journal of Endocrinology Dec 2021Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders.... (Review)
Review
Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.
Topics: Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Lansoprazole; Life Style; Obesity; Risk Factors; Sleep; Sleep Wake Disorders; Time Factors
PubMed: 34779405
DOI: 10.1530/JOE-21-0155 -
Gastroenterology Jan 2023For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than PPIs, but data on its efficacy for erosive esophagitis are limited.
METHODS
Adults with erosive esophagitis were randomized to once-daily vonoprazan, 20 mg, or lansoprazole, 30 mg, for up to 8 weeks. Patients with healing were rerandomized to once-daily vonoprazan, 10 mg, vonoprazan, 20 mg, or lansoprazole, 15 mg, for 24 weeks. Primary end points, percentage with healing by week 8 endoscopy, and maintenance of healing at week 24 endoscopy, were assessed in noninferiority comparisons (noninferiority margins, 10%), with superiority analyses prespecified if noninferiority was demonstrated. Analyses of primary and secondary end points were performed using fixed-sequence testing procedures.
RESULTS
Among 1024 patients in the healing phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the exploratory analysis of healing (92.9 vs 84.6%; difference, 8.3%; 95% confidence interval [CI], 4.5%-12.2%). Secondary analyses showed vonoprazan was noninferior in heartburn-free days (difference, 2.7%; 95% CI, -1.6% to 7.0%), and superior in healing Los Angeles Classification Grade C/D esophagitis at week 2 (difference, 17.6%; 95% CI, 7.4%-27.4%). Among 878 patients in the maintenance phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the secondary analysis of maintenance of healing (20 mg vs lansoprazole: difference, 8.7%; 95% CI, 1.8%-15.5%; 10 mg vs lansoprazole: difference, 7.2%; 95% CI, 0.2%-14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20 mg vs lansoprazole: difference, 15.7%; 95% CI, 2.5%-28.4%; 10 mg vs lansoprazole: difference, 13.3%; 95% CI, 0.02%-26.1%).
CONCLUSIONS
Vonoprazan was noninferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov: NCT04124926).
Topics: Adult; Humans; Lansoprazole; Pyrroles; Sulfonamides; Esophagitis; Proton Pump Inhibitors; Peptic Ulcer; Treatment Outcome
PubMed: 36228734
DOI: 10.1053/j.gastro.2022.09.041 -
Gastroenterology Sep 2022Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe.
METHODS
In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients.
RESULTS
A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P < .001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P < .001; difference 37.7%; 95% CI, 20.5-52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P < .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05).
CONCLUSION
Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population.
CLINICALTRIALS
gov; NCT04167670.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome; United States
PubMed: 35679950
DOI: 10.1053/j.gastro.2022.05.055 -
International Journal of Molecular... Sep 2022Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+... (Review)
Review
Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use... (Review)
Review
Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of . PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.
PubMed: 35222047
DOI: 10.3389/fphar.2022.839972 -
Lancet (London, England) Nov 2022Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against... (Randomized Controlled Trial)
Randomized Controlled Trial
Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.
BACKGROUND
Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding.
METHODS
We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96.
FINDINGS
Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9-6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41-2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62-4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14-0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55-3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients).
INTERPRETATION
H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term.
FUNDING
National Institute for Health and Care Research Health Technology Assessment.
Topics: Humans; Aged; Helicobacter pylori; Helicobacter Infections; Helicobacter; Aspirin; Hot Temperature; Peptic Ulcer Hemorrhage; Peptic Ulcer; Clarithromycin; Primary Health Care; Primary Prevention; Drug Therapy, Combination; Anti-Bacterial Agents
PubMed: 36335970
DOI: 10.1016/S0140-6736(22)01843-8 -
JAMA Network Open Oct 2023The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates...
IMPORTANCE
The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes.
OBJECTIVE
To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021.
EXPOSURE
Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications.
RESULTS
Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.
Topics: Adult; Humans; Male; Aged; Female; Lansoprazole; Ceftriaxone; Cohort Studies; Retrospective Studies; Arrhythmias, Cardiac; Heart Arrest; Proton Pump Inhibitors; Inpatients; Ontario
PubMed: 37883084
DOI: 10.1001/jamanetworkopen.2023.39893 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
Alimentary Pharmacology & Therapeutics Sep 2020Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders.
AIMS
To assess whether tegoprazan is non-inferior to lansoprazole in terms of efficacy and safety in patients with gastric ulcers.
METHODS
In this phase 3, double-blind, active control, multicentre study, 306 gastric ulcer patients were randomised to one of three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg once daily for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed ulcers confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms and safety were assessed.
RESULTS
In the full analysis set, the cumulative healing rates at week 8 were 94.8% (91/96) for the tegoprazan 50 mg, 95.0% (94/99) for the tegoprazan 100 mg and 95.7% (89/93) for the lansoprazole 30 mg groups. At week 4, the respective healing rates were 90.6% (87/96), 91.9% (91/99), and 89.2% (83/93). In per protocol analysis, 4-week healing rates were 95.4% (84/88), 94.6% (88/93) and 92.9% (79/85) for tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg, respectively. Both doses of tegoprazan were non-inferior to lansoprazole in ulcer healing at 4 and 8 weeks. The incidence of drug-related treatment-emergent adverse events did not differ among groups. The increase in serum gastrin concentration was not higher in tegoprazan-treated patients than in lansoprazole-treated patients.
CONCLUSIONS
Tegoprazan 50 or 100 mg were not inferior to lansoprazole 30 mg once daily in the treatment of gastric ulcers.
Topics: Adult; Aged; Anti-Ulcer Agents; Benzene Derivatives; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Imidazoles; Lansoprazole; Male; Middle Aged; Potassium; Proton Pump Inhibitors; Republic of Korea; Stomach Ulcer; Treatment Outcome; Wound Healing
PubMed: 32701188
DOI: 10.1111/apt.15865