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The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
World Journal of Gastroenterology Aug 2019Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis...
BACKGROUND
Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided.AIMSTo study the published evidence and systematically review the literature on the prevention and treatment for PEP.
METHODS
A systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms "Post endoscopic retrograde cholangiopancreatography pancreatitis" AND "prevention" through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies.
RESULTS
726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors; (2) pharmacoprevention; and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results.
CONCLUSION
Prevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.
Topics: Administration, Rectal; Anti-Inflammatory Agents; Biliary Tract Diseases; Catheterization; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Humans; Pancreas; Pancreatitis; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Preoperative Care; Risk Assessment; Risk Factors; Somatostatin; Sphincter of Oddi; Stents
PubMed: 31413535
DOI: 10.3748/wjg.v25.i29.4019 -
Journal of Diabetes Research 2019To compare the efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus (GDM), a meta-analysis of randomized controlled trials... (Meta-Analysis)
Meta-Analysis
To compare the efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus (GDM), a meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Embase, CINAHL, Web of Science, and Cochrane Library to November 13, 2018, were searched for RCT adjusted estimates of the efficacy and safety of metformin, glyburide, and insulin treatments in GDM patients. There were 41 studies involving 7703 GDM patients which were included in this meta-analysis; 12 primary outcomes and 24 secondary outcomes were detected and analyzed. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (RR, 0.57; 95% CI, 0.45 to 0.72; < 0.001), NICU admission (RR, 0.75; 95% CI, 0.64 to 0.87; < 0.001), neonatal hypoglycemia (RR, 0.57; 95% CI, 0.49 to 0.66; < 0.001), and macrosomia (RR, 0.68; 95% CI, 0.55 to 0.86; < 0.05). To the outcomes of birth weight and gestational age at delivery, insulin had a significant increase when compared with metformin (MD, 114.48; 95% CI, 37.32 to 191.64; < 0.01; MD, 0.23; 95% CI, 0.12 to 0.34; < 0.001; respectively). Of the two groups between glyburide and metformin, metformin had lower gestational weight gain compared with glyburide (MD, 1.67; 95% CI, 0.26 to 3.07; < 0.05). Glyburide had a higher risk of neonatal hypoglycemia compared with insulin (RR, 1.76; 95% CI, 1.32 to 2.36; < 0.001). This meta-analysis found that metformin could be a safe and effective treatment for GDM. However, clinicians should pay attention on the long-term offspring outcomes of the relative data with GDM patients treated with metformin. Compared with insulin, glyburide had a higher increase of neonatal hypoglycemia. The use of glyburide in pregnancy for GDM women appears to be unclear.
Topics: Adult; Biomarkers; Blood Glucose; Diabetes, Gestational; Female; Glyburide; Humans; Hypoglycemic Agents; Insulin; Metformin; Patient Safety; Pregnancy; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Young Adult
PubMed: 31781670
DOI: 10.1155/2019/9804708 -
Journal of Translational Medicine Jul 2023This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
The effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials.
OBJECTIVE
This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs).
METHODS
PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR).
RESULTS
Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = - 0.331, 95% CI - 0.424 to - 0.238, P < 0.001), insulin (SMD = - 0.185, 95% CI - 0.313 to - 0.056, P = 0.005), HbA1c (SMD = - 0.421, 95% CI - 0.584 to - 0.258, P < 0.001), and HOMA-IR (SMD = - 0.224, 95% CI - 0.342 to - 0.105, P < 0.001). Further subgroup analyses showed that the effect was larger in the subgroups of Caucasians, high baseline body mass index (BMI ≥ 30.0 kg/m), Bifidobacterium and food-type probiotics (P < 0.050).
CONCLUSION
This study supported that probiotics supplementation had favourable effects on glycaemic control in T2DM patients. It may be a promising adjuvant therapy for patients with T2DM.
Topics: Adult; Humans; Glycated Hemoglobin; Blood Glucose; Glycemic Control; Diabetes Mellitus, Type 2; Probiotics; Insulin Resistance; Insulin; Randomized Controlled Trials as Topic
PubMed: 37415167
DOI: 10.1186/s12967-023-04306-0 -
BMJ (Clinical Research Ed.) Aug 2019To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism. (Meta-Analysis)
Meta-Analysis
Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism.
DESIGN
Systematic review and meta-analyses.
DATA SOURCES
Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews.
ELIGIBILITY CRITERIA
Randomised controlled trials of at least 24 weeks' duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA), and/or homoeostatic model assessment for insulin resistance (HOMA-IR).
DATA SYNTHESIS
Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE.
RESULTS
83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA mean difference -0.02%, 95% confidence interval -0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, -4.34 to 6.37, pmol/L; HOMA-IR 0.06, -0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism.
CONCLUSIONS
This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017064110.
Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Dietary Supplements; Fasting; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Primary Prevention; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 31434641
DOI: 10.1136/bmj.l4697 -
The Cochrane Database of Systematic... Jun 2020Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM. Despite this, the effects of metformin on patient-important outcomes are still not clarified.
OBJECTIVES
To assess the effects of metformin monotherapy in adults with T2DM.
SEARCH METHODS
We based our search on a systematic report from the Agency for Healthcare Research and Quality, and topped-up the search in CENTRAL, MEDLINE, Embase, WHO ICTRP, and ClinicalTrials.gov. Additionally, we searched the reference lists of included trials and systematic reviews, as well as health technology assessment reports and medical agencies. The date of the last search for all databases was 2 December 2019, except Embase (searched up 28 April 2017).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with at least one year's duration comparing metformin monotherapy with no intervention, behaviour changing interventions or other glucose-lowering drugs in adults with T2DM.
DATA COLLECTION AND ANALYSIS
Two review authors read all abstracts and full-text articles/records, assessed risk of bias, and extracted outcome data independently. We resolved discrepancies by involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall certainty of the evidence by using the GRADE instrument.
MAIN RESULTS
We included 18 RCTs with multiple study arms (N = 10,680). The percentage of participants finishing the trials was approximately 58% in all groups. Treatment duration ranged from one to 10.7 years. We judged no trials to be at low risk of bias on all 'Risk of bias' domains. The main outcomes of interest were all-cause mortality, serious adverse events (SAEs), health-related quality of life (HRQoL), cardiovascular mortality (CVM), non-fatal myocardial infarction (NFMI), non-fatal stroke (NFS), and end-stage renal disease (ESRD). Two trials compared metformin (N = 370) with insulin (N = 454). Neither trial reported on all-cause mortality, SAE, CVM, NFMI, NFS or ESRD. One trial provided information on HRQoL but did not show a substantial difference between the interventions. Seven trials compared metformin with sulphonylureas. Four trials reported on all-cause mortality: in three trials no participant died, and in the remaining trial 31/1454 participants (2.1%) in the metformin group died compared with 31/1441 participants (2.2%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on SAE: in two trials no SAE occurred (186 participants); in the other trial 331/1454 participants (22.8%) in the metformin group experienced a SAE compared with 308/1441 participants (21.4%) in the sulphonylurea group (very low-certainty evidence). Two trials reported on CVM: in one trial no CVM was observed and in the other trial 4/1441 participants (0.3%) in the metformin group died of cardiovascular reasons compared with 8/1447 participants (0.6%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on NFMI: in two trials no NFMI occurred, and in the other trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 15/1441 participants (1.0%) in the sulphonylurea group (very low-certainty evidence). One trial reported no NFS occurred (very low-certainty evidence). No trial reported on HRQoL or ESRD. Seven trials compared metformin with thiazolidinediones (very low-certainty evidence for all outcomes). Five trials reported on all-cause mortality: in two trials no participant died; the overall RR was 0.88, 95% CI 0.55 to 1.39; P = 0.57; 5 trials; 4402 participants). Four trials reported on SAE, the RR was 0,95, 95% CI 0.84 to 1.09; P = 0.49; 3208 participants. Four trials reported on CVM, the RR was 0.71, 95% CI 0.21 to 2.39; P = 0.58; 3211 participants. Three trial reported on NFMI: in two trials no NFMI occurred and in one trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 25/1456 participants (1.7%) in the thiazolidinedione group. One trial reported no NFS occurred. No trial reported on HRQoL or ESRD. Three trials compared metformin with dipeptidyl peptidase-4 inhibitors (one trial each with saxagliptin, sitagliptin, vildagliptin with altogether 1977 participants). There was no substantial difference between the interventions for all-cause mortality, SAE, CVM, NFMI and NFS (very low-certainty evidence for all outcomes). One trial compared metformin with a glucagon-like peptide-1 analogue (very low-certainty evidence for all reported outcomes). There was no substantial difference between the interventions for all-cause mortality, CVM, NFMI and NFS. One or more SAEs were reported in 16/268 (6.0%) of the participants allocated to metformin compared with 35/539 (6.5%) of the participants allocated to a glucagon-like peptide-1 analogue. HRQoL or ESRD were not reported. One trial compared metformin with meglitinide and two trials compared metformin with no intervention. No deaths or SAEs occurred (very low-certainty evidence) no other patient-important outcomes were reported. No trial compared metformin with placebo or a behaviour changing interventions. Four ongoing trials with 5824 participants are likely to report one or more of our outcomes of interest and are estimated to be completed between 2018 and 2024. Furthermore, 24 trials with 2369 participants are awaiting assessment.
AUTHORS' CONCLUSIONS
There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs influences patient-important outcomes.
Topics: Adult; Carbamates; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Metformin; Myocardial Infarction; Piperidines; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Sulfonylurea Compounds
PubMed: 32501595
DOI: 10.1002/14651858.CD012906.pub2 -
Frontiers in Endocrinology 2023A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and... (Meta-Analysis)
Meta-Analysis
PURPOSE
A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.
METHODS
A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.).
RESULTS
A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.
CONCLUSION
Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.
Topics: Humans; Cholecystitis; Diabetes Mellitus, Type 2; Insulin Glargine; Obesity; Pancreatitis; Cholelithiasis
PubMed: 37908750
DOI: 10.3389/fendo.2023.1214334 -
PloS One 2023Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study.
METHODS
Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software.
RESULTS
In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs.
CONCLUSION
In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Insulin; Weight Loss; Obesity; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor
PubMed: 37141329
DOI: 10.1371/journal.pone.0285197 -
Journal of Gastrointestinal and Liver... Mar 2021Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB.
METHODS
We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology.
RESULTS
We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others.
CONCLUSIONS
In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.
Topics: Adult; Aged; Blood Transfusion; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Length of Stay; Liver Cirrhosis; Male; Middle Aged; Octreotide; Recurrence; Somatostatin; Terlipressin; Treatment Outcome; Vasopressins
PubMed: 33723542
DOI: 10.15403/jgld-3191 -
PLoS Medicine Aug 2019Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However,... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown.
METHODS AND FINDINGS
PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies (n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies (n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies (n = 411 infants) reported measures of infant growth (18-24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I2 = 4%, p = 0.03). Three studies (n = 520 children) reported mid-childhood growth parameters (5-9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m2, 95% CI 0.23 to 1.33, I2 = 7%, p = 0.005) following metformin exposure than following insulin exposure, although the difference in absolute weights between the groups was not significantly different (p = 0.09). Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers. Study limitations include heterogeneity in metformin dosing, heterogeneity in diagnostic criteria for GDM, and the scarcity of reporting of childhood outcomes.
CONCLUSIONS
Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy. Despite lower average birth weight, metformin-exposed children appear to experience accelerated postnatal growth, resulting in heavier infants and higher BMI by mid-childhood compared to children whose mothers were treated with insulin. Such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes. This suggests a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure. This review protocol was registered with PROSPERO under registration number CRD42018117503.
Topics: Child Development; Child, Preschool; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Metformin; Pregnancy
PubMed: 31386659
DOI: 10.1371/journal.pmed.1002848