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Journal of Gastrointestinal and Liver... Jun 2024Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and surveillance for neoplasia. We performed a systematic review of randomised trials of various bowel preparations for colonoscopy in IBD.
METHODS
We searched various electronic databases (PubMed, Embase, and CENTRAL) for studies reporting about the use of various strategies to improve colonoscopy preparation in IBD. We included only randomized clinical trials (RCTs). A network meta-analysis was done using a frequentist approach to compare the effectiveness of various bowel preparations. The risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcome parameters like compliance, tolerance, acceptance, and adverse effects were assessed qualitatively.
RESULTS
Seven RCTs reporting about 960 patients were included. On comparison with 4 liter (L) of poliethylen glycol (PEG), oral sulfate solution (OR=1.1, 95%CI: 0.65-1.86); PEG2L/Ascorbate (OR=0.98, 95%CI: 0.65-1.48); PEG1L (OR=1, 95%CI: 0.55-1.81); PEG2L plus bisacodyl (OR=1.08, 95%CI: 0.71-1.65); PEG4L plus simethicone (OR=1, 95%CI: 0.67-1.50); PEG/ sodium picosulfate and magnesium citrate (SPMC) 1.5L (OR=0.99, 95%CI: 0.55-1.78); SPMC 2L (OR=1.09, 95%CI: 0.61-1.97) had similar effectiveness. Three RCTs reported compliance, five RCTs reported tolerance, two studies reported patient acceptance and five RCTs reported data on the willingness of patients to repeat the procedure in the future. Low-volume preparations had better compliance, tolerance, acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcomes after colonoscopy like cecal intubation rate, and change in electrolyte levels were found.
CONCLUSION
Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.
Topics: Humans; Colonoscopy; Randomized Controlled Trials as Topic; Cathartics; Inflammatory Bowel Diseases; Network Meta-Analysis
PubMed: 38944852
DOI: 10.15403/jgld-5433 -
The Cochrane Database of Systematic... Jun 2024Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence suggests that metformin targets a number of pathways that lead to chronic kidney damage, and long-term use may, therefore, slow the rate of kidney function decline and chronic kidney disease (CKD) progression.
OBJECTIVES
To evaluate the effect of metformin therapy on kidney function decline in patients with CKD with or without diabetes mellitus and assess the safety and dose tolerability in this population.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2023 with assistance from an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that reported kidney-related outcomes with a minimum duration of 12 months delivery of the metformin intervention and whose eligibility criteria included adult participants with either i) a diagnosis of CKD of any aetiology and/or ii) those with a diagnosis of diabetes mellitus. Comparisons included placebo, no intervention, non-pharmacological interventions, other antidiabetic medications or any other active control. Studies that included patients on any modality of kidney replacement therapy were excluded.
DATA COLLECTION AND ANALYSIS
Two authors independently carried out data extraction using a standard data extraction form. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
This review included 11 studies reporting on 8449 randomised participants. Studies were conducted in patient populations with Autosomal Dominant Polycystic Kidney Disease (ADPKD) (four studies) or diabetes mellitus (seven studies). Six studies compared metformin with no active control, four studies compared metformin with active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), and one study included treatment arms that randomised to either metformin, diet and lifestyle modifications, or other antidiabetic therapies. The risk of bias in included studies varied; two studies were abstract-only publications and were judged to have a high risk of bias in most domains. Other included publications were judged to have a low risk of bias in most domains. Across comparisons, GRADE evaluations for most outcomes were judged as low or very low certainty, except for those relating to side effects, tolerance, and withdrawals, which were judged as moderate certainty. The evidence suggests that compared to placebo, metformin may result in i) a slightly smaller decline in kidney function (3 studies, 505 participants: MD 1.92 mL/min, 95% CI 0.33 to 3.51; I = 0%; low certainty), ii) very uncertain effects on the incidence of kidney failure (1 study, 753 participants: RR 1.20, 95% CI 0.17 to 8.49), iii) little or no effect on death (3 studies, 865 participants: RR 1.00, 95% CI 0.76 to 1.32; I = 0%; moderate certainty), iv) little or no effect on the incidence of serious adverse events (3 studies, 576 participants: RR 1.15, 95% CI 0.76 to 1.72; I = 0%; moderate certainty), and v) likely higher incidence of intolerance leading to study withdrawal than placebo (4 studies, 646 participants: RR 2.19, 95% CI 1.46 to 3.27; I = 0%; moderate certainty). The certainty of the evidence for proteinuria was very uncertain. Compared to other active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), metformin i) demonstrated very uncertain effects on kidney function decline, ii) may result in little or no difference in death (3 studies, 5608 participants: RR 0.95 95% CI 0.63 to 1.43; I = 0%; low certainty), iii) probably results in little or no difference in intolerance leading to study withdrawal (3 studies, 5593 participants: RR 0.92, 95% CI, 0.79 to 1.08; I = 0%; moderate certainty), iv) probably results in little or no difference in the incidence of serious adverse events (2 studies, 5545 participants: RR 1.16, 95% CI 0.79 to 1.71; I = 0%; moderate certainty), and v) may increase the urinary albumin-creatinine ratio (2 studies, 3836 participants: MD 14.61, 95% CI 8.17 to 21.05; I = 0%; low certainty). No studies reported the incidence of kidney failure.
AUTHORS' CONCLUSIONS
This review highlights the lack of RCTs reporting on the effects of metformin on kidney function, particularly in patients with CKD. Future research in this field requires adequately powered RCTs comparing metformin to placebo or standard care in those with CKD. Seven ongoing studies were identified in this review, and future updates, including their findings, may further inform the results of this review.
Topics: Metformin; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Disease Progression; Hypoglycemic Agents; Glomerular Filtration Rate; Diabetes Mellitus, Type 2; Adult; Bias
PubMed: 38837240
DOI: 10.1002/14651858.CD013414.pub2 -
Journal of Cardiovascular Medicine... Jul 2024We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. (Meta-Analysis)
Meta-Analysis
AIMS
We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients.
METHODS
A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated.
RESULTS
We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001).
CONCLUSION
Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.
Topics: Humans; Cardiomyopathy, Hypertrophic; Treatment Outcome; Randomized Controlled Trials as Topic; Ventricular Function, Left; Stroke Volume; Middle Aged; Male; Female; Natriuretic Peptide, Brain; Pyrimidines; Exercise Tolerance; Biomarkers; Adult; Recovery of Function; Oxygen Consumption; Aged; Benzylamines; Uracil
PubMed: 38814051
DOI: 10.2459/JCM.0000000000001638 -
Medicine May 2024The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes.
METHODS
For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023.
RESULTS
Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)].
CONCLUSIONS
In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results.
Topics: Humans; Orlistat; Prediabetic State; Diabetes Mellitus, Type 2; Blood Glucose; Disease Progression; Anti-Obesity Agents; Randomized Controlled Trials as Topic; Lactones
PubMed: 38787971
DOI: 10.1097/MD.0000000000038354 -
Biochemical Pharmacology Jul 2024Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.
Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.
Topics: Animals; Mice; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Environmental Exposure; Environmental Pollutants; Glycemic Control; Persistent Organic Pollutants; Weight Loss; Disease Models, Animal; Rats
PubMed: 38782075
DOI: 10.1016/j.bcp.2024.116300 -
Water Research Jul 2024Micro/nano-plastics (MNPs), as emerging persistent pollutants, are threatening freshwater ecosystems worldwide. Microalgae are important primary producers at the base of... (Meta-Analysis)
Meta-Analysis Review
Meta-analysis for systematic review of global micro/nano-plastics contamination versus various freshwater microalgae: Toxicological effect patterns, taxon-specific response, and potential eco-risks.
Micro/nano-plastics (MNPs), as emerging persistent pollutants, are threatening freshwater ecosystems worldwide. Microalgae are important primary producers at the base of trophic level and susceptible to MNPs contamination, possibly resulting in further contamination in higher trophic levels and water quality. This study conducted a systematic review of 1071 observations from 63 publications, utilizing meta-analysis and subgroup analysis to investigate the toxicological effect patterns of MNPs parameters (size, concentration, and type) on microalgae. We also explored the potential eco-risks of certain specific MNPs parameters and subtle variations in the response of various microalgae taxa to MNPs. Results suggested that microplastics significantly inhibited microalgal photosynthesis, while nano-plastics induced more severe cell membrane damage and promoted toxin-release. Within a certain range of concentrations (0∼50 mg/L), rising MNPs concentration progressively inhibited microalgal growth and chlorophyll-a content, and progressively enhanced toxin-release. Among MNPs types, polyamide caused higher growth inhibition and more severe lipid peroxidation, and polystyrene induced more toxin-release, whereas polyethylene terephthalate and polymethyl methacrylate posed minimal effects on microalgae. Moreover, Bacillariophyta growth was inhibited most significantly, while Chlorophyta displayed strong tolerance and Cyanophyta possessed strong adaptive and exceptional resilience. Particularly, Komvophoron, Microcystis, Nostoc, Scenedesmus, and Gomphonema were more tolerant and might dominate freshwater microalgal communities under MNPs contamination. These results are crucial for acquiring the fate of freshwater microalgae under various MNPs contamination, identifying dominant microalgae, and reasonably assessing and managing involved eco-risks.
Topics: Microalgae; Fresh Water; Water Pollutants, Chemical; Microplastics; Plastics; Photosynthesis
PubMed: 38761590
DOI: 10.1016/j.watres.2024.121706 -
Minerva Medica Apr 2024Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is...
INTRODUCTION
Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders.
EVIDENCE ACQUISITION
This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders.
EVIDENCE SYNTHESIS
The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence.
CONCLUSIONS
Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.
Topics: Melatonin; Humans; Delayed-Action Preparations; Sleep Initiation and Maintenance Disorders; Circadian Rhythm; Sleep Disorders, Circadian Rhythm; Neurodevelopmental Disorders; Mood Disorders; Sleep Wake Disorders; Sleep Quality; Neurocognitive Disorders
PubMed: 38713204
DOI: 10.23736/S0026-4806.24.09303-0 -
Alimentary Pharmacology & Therapeutics Jun 2024The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real-world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment.
AIM
To provide real-world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD.
METHODS
We conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta-analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)-specifically infliximab and adalimumab.
RESULTS
Among 63 observational studies, vedolizumab had the highest 1-year persistence in UC (73.8%, 95% CI: 70.0%-77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%-82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19-1.41) for UC and 1.14 (95% CI: 1.09-1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07-1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14-1.54).
CONCLUSION
This meta-analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.
Topics: Humans; Gastrointestinal Agents; Ustekinumab; Crohn Disease; Colitis, Ulcerative; Inflammatory Bowel Diseases; Antibodies, Monoclonal, Humanized; Treatment Outcome; Observational Studies as Topic; Infliximab; Piperidines; Antibodies, Monoclonal; Pyrimidines
PubMed: 38651771
DOI: 10.1111/apt.18006 -
Biomedical Reports May 2024Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In...
Effects of abrocitinib on pruritus and eczema symptoms and tolerance in patients with moderate‑to‑severe atopic dermatitis in randomized, double‑blind and placebo‑controlled trials: A systematic review and a meta‑analysis.
Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo. Specifically, randomized controlled trials (RCTs) of abrocitinib compared with placebo for the treatment of moderate-to-severe AD were searched on Pubmed, E.B. Stephens Company, China National Knowledge Infrastructure, Wanfang Medical network, Web of Science and related Clinical Trials Registry up to November 2023. In total, two researchers evaluated the quality of the included literature according to the Cochrane Handbook of Systematic Reviews. RevMan 5.3 software was used to conduct a meta-analysis of the efficacy and safety indicators in a cross-comparison of the effects exerted by placebo and 100 and 200 mg abrocitinib. A total of 1,825 patients with moderate-to-severe AD were included across five double-blind, placebo RCTs. Compared with the placebo group, during the double-blind trial period, significant improvements were observed in the investigator's global assessment score, response rate of eczema area and severity index (EASI)-50, EASI-75, EASI-90 and pruritus numerical rating scale (P-NRS) in the 100 and 200 mg abrocitinib groups (P<0.05). However, pairwise control analysis of the 100 and 200 mg group yielded significant differences (P<0.05) in all of the aforementioned therapeutic indicators except for the P-NRS score. In terms of safety, compared with the placebo group, there were significantly higher incidence of nausea, upper respiratory tract viral infection, infections and infestations in the 100 mg abrocitinib group (P<0.05). In addition, there were significantly higher incidence of nausea, gastrointestinal disorder, headache and dizziness in the 200 mg group (P<0.05). There were also significant differences in the incidence of nausea, gastrointestinal disorder and dizziness between the 100 and 200 mg groups (P<0.05). For patients with moderate-to-severe AD, oral administration of 100 or 200 mg abrocitinib once/day was concluded to ameliorate skin pruritus and eczema symptoms to varying degrees, with the efficacy significantly superior at the 200 mg dose. However, the risk of a number of adverse reactions, such as headache, dizziness, nausea and gastrointestinal dysfunction, is also significantly increased. Therefore, patients should be made aware of the risk of adverse drug effects prior to the administration of long-term high abrocitinib doses. Furthermore, large-scale, multi-center, rigorous clinical trials remain necessary to validate the findings from the present study.
PubMed: 38628626
DOI: 10.3892/br.2024.1772 -
Peptides Jul 2024In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1-42) in human studies with... (Review)
Review
In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1-42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1-42) administration. A total of 67 studies were included. Study duration ranged from 30 min to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes. Of the included studies, 78% did not mention safety events, 10% of the studies reported that no safety events were observed in relation to GIP administration, and 15% of the studies reported safety events in relation to GIP administration with most frequently reported event being a moderate and transient increased heart rate. Gastrointestinal safety events, and changes in blood pressure were also reported. Plasma concentration of active GIP(1-42) increased linearly with dose independent of participant phenotype. There was no significant correlation between achieved maximal concentration of GIP(1-42) and reported safety events. Clearance rates of GIP(1-42) were similar between participant groups. In conclusion, the available data indicate that GIP(1-42) in short-term (up to 6 days) infusion studies is generally well-tolerated. The long-term safety of continuous GIP(1-42) administration is unknown.
Topics: Humans; Gastric Inhibitory Polypeptide; Peptide Fragments; Diabetes Mellitus, Type 2; Glucose Intolerance; Diabetes Mellitus, Type 1
PubMed: 38615716
DOI: 10.1016/j.peptides.2024.171214