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Transplantation Reviews (Orlando, Fla.) Jan 2019Weight gain and obesity can increase liver transplant (LTx) recipients' disease burden. We aimed to summarize and synthesize the evidence on pre- and post-transplant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Weight gain and obesity can increase liver transplant (LTx) recipients' disease burden. We aimed to summarize and synthesize the evidence on pre- and post-transplant factors related to post-LTx BMI, weight gain, and obesity.
METHODS
For this systematic review and meta-analysis we searched Medline (PubMed), Cochrane library, CINAHL, PsycINFO, and EMBASE for quantitative studies on 6 classes of factors (i.e., genetic, sociodemographic, behavioral, biomedical, psychological, and environmental) linked to body weight parameters in adult first-time LTx patients. A 19-item instrument was used for quality assessment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for relationships investigated in ≥5 studies. Factors investigated in <5 studies were summarized and described.
RESULTS
Of 16,495 articles retrieved, 43 assessed factors in LTx. These examined 82 mainly biomedical and sociodemographic factors. However, variation between definitions allowed inclusion of only 2 factors (i.e., tacrolimus, cyclosporine) in our meta-analyses of 6 studies examining a shared parameter for body weight (median patient sample: 171 (range: 63-455); Europe n = 3; United States n = 3; publication years: 1997-2015). Neither tacrolimus (OR, 0.75; 95% CI, 0.47-1.21; p = 0.24) nor cyclosporine (OR, 1.40; 95% CI, 0.89-2.18; p = 0.14) were related significantly with post-LTx obesity.
CONCLUSIONS
Evidence on modifiable factors related to post-LTx body weight parameters is still scarce, as definition variability limits data extraction and pooling for meta-analyses. To facilitate future research, studies should apply theoretical frameworks to guide their study design, select variables of interest and systematically examine interrelationships among selected factors.
Topics: Body Mass Index; End Stage Liver Disease; Humans; Liver Transplantation; Obesity; Risk Factors; Weight Gain
PubMed: 30472154
DOI: 10.1016/j.trre.2018.10.002 -
PloS One 2015End-stage kidney disease (ESKD) patients are often prescribed multiple medications. Together with a demanding weekly schedule of dialysis sessions, increased number of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage kidney disease (ESKD) patients are often prescribed multiple medications. Together with a demanding weekly schedule of dialysis sessions, increased number of medicines and associated regimen complexity pre-dispose them at high risk of medication nonadherence. This review summarizes existing literature on nonadherence and identifies factors associated with nonadherence to medication therapy in patients undergoing haemodialysis.
METHODS
A comprehensive search of PubMed, Embase, CINAHL, PsycInfo, and Cochrane Database of Systematic Reviews covering the period from 1970 through November 2014 was performed following a predefined inclusion and exclusion criteria. Reference lists from relevant materials were reviewed. Data on study characteristics, measures of nonadherence, prevalence rates and factors associated with nonadherence were collected. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was followed in conducting this systematic review.
RESULTS
Of 920 relevant publications, 44 were included. The prevalence of medication nonadherence varied from 12.5% to 98.6%, with widespread heterogeneity in measures and definitions employed. Most common patient-related factors significantly associated with nonadherence were younger age, non-Caucasian ethnicity, illness interfering family life, being a smoker, and living single and being divorced or widowed. Similarly, disease-related factors include longevity of haemodialysis, recurrent hospitalization, depressive symptoms and having concomitant illness like diabetes and hypertension. Medication-related factors such as daily tablet count, total pill burden, number of phosphate binders prescribed and complexity of medication regimen were also associated with poor adherence.
CONCLUSIONS
A number of patient-, disease-, and medication-related factors are associated with medication nonadherence in haemodialysis patients. Clinicians should be aware of such factors so that adherence to medications can be optimised in haemodialysis patients. Future research should be directed towards well-designed prospective longitudinal studies developing standard definitions and validating available measurement tools, while focusing on the role of additional factors such as psychosocial and behavioural factors in predicting nonadherence to medications.
Topics: Adolescent; Adult; Aged; Female; Humans; Kidney Failure, Chronic; Male; Medication Adherence; Middle Aged; Polypharmacy; Renal Dialysis; Risk Factors; Young Adult
PubMed: 26636968
DOI: 10.1371/journal.pone.0144119 -
Health Psychology Review Dec 2023The relationships between temporal self-regulation theory (TST) constructs (intention, behavioural prepotency and self-regulatory capacity) and medication adherence... (Meta-Analysis)
Meta-Analysis
The relationships between temporal self-regulation theory (TST) constructs (intention, behavioural prepotency and self-regulatory capacity) and medication adherence should be established before further applying the theory to adherence. Searches of PsychINFO, Medline, EMBASE, CINAHL and Web of Science were conducted in 2019 (updated November 2021). Studies had to be original quantitative research, assessed the relationship between one of the constructs and adherence in one illness, and used an adult population. The risk of bias was assessed using the NHLBI Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Three meta-analyses were conducted using . Moderation analyses were also conducted. A total of 57 articles (60 studies) with 13,995 participants were included, with 7 studies included in more than one analysis. Results identified significant correlations between intention ( = .369, [95% CI: .25, .48]), behavioural prepotency ( = .332, [95% CI: .18, .48]), self-regulatory capacity ( = .213, [95% CI: .10, .32]) and adherence. There was some evidence of publication bias and no significant moderators. No studies explored the interactions in the theory, so whilst the constructs adequately predict adherence, future research should apply the theory to adherence in a specific illness to assess these relationships. Pre-registered on Prospero: CRD42019141395.
Topics: Adult; Humans; Cross-Sectional Studies; Medication Adherence; Self-Control
PubMed: 36154853
DOI: 10.1080/17437199.2022.2127831 -
Expert Opinion on Drug Safety Jun 2024The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. (Meta-Analysis)
Meta-Analysis
Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications.
RESEARCH DESIGN AND METHODS
A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes.
RESULTS
The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; = 0.03).
CONCLUSION
Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.
Topics: Humans; Pancreatic Neoplasms; Pancreatitis; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Adverse Drug Reaction Reporting Systems; Retrospective Studies; Risk; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37986140
DOI: 10.1080/14740338.2023.2284992 -
The Cochrane Database of Systematic... May 2020Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This review supersedes a previous, out-of-date review that evaluated all potential therapies for preventing recurrent pregnancy loss in women with aPL. The current review focusses on a narrower scope because current clinical practice is restricted to using aspirin or heparins, or both for women with aPL in an attempt to reduce pregnancy complications.
OBJECTIVES
To assess the effects of aspirin or heparin, or both for improving pregnancy outcomes in women with persistent (on two separate occasions) aPL, either lupus anticoagulant (LAC), anticardiolipin (aCL) or aβ-glycoprotein-I antibodies (aβGPI) or a combination, and recurrent pregnancy loss (two or more, which do not have to be consecutive).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 June 2019), and reference lists of retrieved studies. Where necessary, we attempted to contact trial authors.
SELECTION CRITERIA
Randomised, cluster-randomised and quasi-randomised controlled trials that assess the effects of aspirin, heparin (either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH]), or a combination of aspirin and heparin compared with no treatment, placebo or another, on pregnancy outcomes in women with persistent aPL and recurrent pregnancy loss were eligible. All treatment regimens were considered.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion criteria and risk of bias. Two review authors independently extracted data and checked them for accuracy and the certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Eleven studies (1672 women) met the inclusion criteria; nine randomised controlled trials and two quasi-RCTs. The studies were conducted in the USA, Canada, UK, China, New Zealand, Iraq and Egypt. One included trial involved 1015 women, all other included trials had considerably lower numbers of participants (i.e. 141 women or fewer). Some studies had high risk of selection and attrition bias, and many did not include sufficient information to judge the risk of reporting bias. Overall, the certainty of evidence is low to very low due to the small numbers of women in the studies and to the risk of bias. The dose and type of heparin and aspirin varied among studies. One study compared aspirin alone with placebo; no studies compared heparin alone with placebo and there were no trials that had a no treatment comparator arm during pregnancy; five studies explored the efficacy of heparin (either UFH or LMWH) combined with aspirin compared with aspirin alone; one trial compared LMWH with aspirin; two trials compared the combination of LMWH plus aspirin with the combination of UFH plus aspirin; two studies evaluated the combination of different doses of heparin combined with aspirin. All trials used aspirin at a low dose. Aspirin versus placebo We are very uncertain if aspirin has any effect on live birth compared to placebo (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71 to 1.25, 1 trial, 40 women, very low-certainty evidence). We are very uncertain if aspirin has any effect on the risk of pre-eclampsia, pregnancy loss, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the child, compared to placebo. We are very uncertain if aspirin has any effect on adverse events (bleeding) in the mother compared with placebo (RR 1.29, 95% CI 0.60 to 2.77, 1 study, 40 women). The certainty of evidence for these outcomes is very low because of imprecision, due to the low numbers of women involved and the wide 95% CIs, and also because of risk of bias. Venous thromboembolism and arterial thromboembolism were not reported in the included studies. Heparin plus aspirin versus aspirin alone Heparin plus aspirin may increase the number of live births (RR 1.27, 95% CI 1.09 to 1.49, 5 studies, 1295 women, low-certainty evidence). We are uncertain if heparin plus aspirin has any effect on the risk of pre-eclampsia, preterm delivery of a live infant, or intrauterine growth restriction, compared with aspirin alone because of risk of bias and imprecision due to the low numbers of women involved and the wide 95% CIs. We are very uncertain if heparin plus aspirin has any effect on adverse events (bleeding) in the mother compared with aspirin alone (RR 1.65, 95% CI 0.19 to 14.03, 1 study, 31 women). No women in either the heparin plus aspirin group or the aspirin alone group had heparin-induced thrombocytopenia, allergic reactions, or venous or arterial thromboembolism. Similarly, no infants had congenital malformations. Heparin plus aspirin may reduce the risk of pregnancy loss (RR 0.48, 95% CI 0.32 to 0.71, 5 studies, 1295 women, low-certainty evidence). When comparing LMWH plus aspirin versus aspirin alone the pooled RR for live birth was 1.20 (95% CI 1.04 to 1.38, 3 trials, 1155 women). In the comparison of UFH plus aspirin versus aspirin alone, the RR for live birth was 1.74 (95% CI 1.28 to 2.35, 2 trials, 140 women).
AUTHORS' CONCLUSIONS
The combination of heparin (UFH or LMWH) plus aspirin during the course of pregnancy may increase live birth rate in women with persistent aPL when compared with aspirin treatment alone. The observed beneficial effect of heparin was driven by one large study in which LMWH plus aspirin was compared with aspirin alone. Adverse events were frequently not, or not uniformly, reported in the included studies. More research is needed in this area in order to further evaluate potential risks and benefits of this treatment strategy, especially among women with aPL and recurrent pregnancy loss, to gain consensus on the ideal prevention for recurrent pregnancy loss, based on a risk profile.
Topics: Abortion, Habitual; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Aspirin; Bias; Drug Therapy, Combination; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Live Birth; Lupus Coagulation Inhibitor; Placebos; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Randomized Controlled Trials as Topic; beta 2-Glycoprotein I
PubMed: 32358837
DOI: 10.1002/14651858.CD012852.pub2 -
Expert Opinion on Investigational Drugs 2023Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long... (Review)
Review
INTRODUCTION
Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.
AREAS COVERED
This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.
EXPERT OPINION
We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Randomized Controlled Trials as Topic; Fatigue Syndrome, Chronic; Drugs, Investigational
PubMed: 37534972
DOI: 10.1080/13543784.2023.2242773 -
AIDS and Behavior Jul 2023Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and... (Review)
Review
Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and substance use. Substance use is associated with reduced adherence to other medications, but associations between substance use and adherence to PrEP are less clear. Thus, the current review 1) systematically evaluates the measurement of substance use and PrEP adherence in studies examining both and 2) summarizes reported findings. Peer-reviewed articles published between 2010 - April 2021 examining associations between substance use and PrEP adherence were reviewed. Fifty studies met inclusion criteria. Assessment of substance use (i.e., mostly via self-reports at baseline) and PrEP adherence (i.e., often via tenofovir diphosphate [TFV-DP] concentration levels at follow-up) varied considerably across studies. Many studies used categorical variables (e.g., substance use: yes/no). Studies using TFV-DP levels defined adherence consistently (i.e., TFV-DP ≥ 700 fmol/punch), with slight variations. Qualitative studies (n = 10) indicated that substance use (mainly alcohol) is related to poorer PrEP adherence. While quantitative findings to date are equivocal for alcohol, there is a pattern of findings linking stimulant use with poorer PrEP adherence. This review reveals four methodological gaps, which can be addressed in future research by: 1) use of uniform benchmarks for substance use measures, 2) prospective assessment for substance use, 3) use of continuous outcome variables wherever possible, and 4) more extensive consideration of potential confounders. Addressing these methodological gaps may help us reach more definitive conclusions regarding associations between substance use and PrEP adherence.
Topics: Male; Humans; Female; HIV Infections; Homosexuality, Male; Tenofovir; Pre-Exposure Prophylaxis; Transgender Persons; Sexual and Gender Minorities; Prospective Studies; Medication Adherence; Substance-Related Disorders; Anti-HIV Agents
PubMed: 36538138
DOI: 10.1007/s10461-022-03948-3 -
Scientific Reports Jan 2024It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term... (Meta-Analysis)
Meta-Analysis
It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people's quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.
Topics: Humans; Chronic Pain; Network Meta-Analysis; Quality of Life; Anti-Inflammatory Agents, Non-Steroidal; Pharmaceutical Preparations
PubMed: 38238384
DOI: 10.1038/s41598-023-49761-3 -
Drug and Alcohol Dependence Apr 2015Increasing use of opioids has led to an increase in the number of pregnant and postpartum women in medication assisted treatment (MAT) for opioid use disorder. (Review)
Review
BACKGROUND
Increasing use of opioids has led to an increase in the number of pregnant and postpartum women in medication assisted treatment (MAT) for opioid use disorder.
METHODS
We (1) conducted a systematic review of published literature on MAT discontinuation (methadone and buprenorphine) in pregnant and postpartum women and (2) determined methadone discontinuation rates in a retrospective cohort (2006-2013) of pregnant and postpartum women in a university affiliated methadone clinic.
RESULTS
We found limited generalizable literature reports of discontinuation rates, with a range of prenatal discontinuation rates from 0 to 33% and rates which spanned various prenatal and postnatal periods from 26 to 64%. In our cohort of 229 women, 251 pregnancies were reported, with a prenatal methadone discontinuation rate of 11.0%. Based on a Cox proportional hazards model controlling for age, pregnancy outcome, and duration of treatment prior to delivery, the probability of methadone discontinuation at or before 6 months postpartum was 56.0%. Duration of methadone treatment prior to delivery was inversely associated with risk for postpartum discontinuation of treatment (HR = 0.98, 95% CI (0.96, 0.99)).
CONCLUSIONS
We conclude that the postpartum period is a time of increased risk for discontinuation of MAT. More accurate assessment of rates of pre- and postpartum MAT discontinuation, as well as further investigation of factors affecting these rates, is warranted. Development and testing of interventions to encourage early prenatal enrollment in MAT and improve postnatal retention in MAT would benefit pregnant women and new mothers with opioid use disorder.
Topics: Buprenorphine; Female; Humans; Kaplan-Meier Estimate; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies
PubMed: 25735465
DOI: 10.1016/j.drugalcdep.2015.02.012 -
The Cochrane Database of Systematic... Aug 2020Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin.
OBJECTIVES
To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS.
SEARCH METHODS
In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately.
MAIN RESULTS
This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events.
AUTHORS' CONCLUSIONS
In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m and BMI > 30kg/m. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.
Topics: Acne Vulgaris; Adolescent; Adult; Body Mass Index; Cardiovascular Diseases; Contraceptives, Oral, Combined; Drug Therapy, Combination; Endometrial Neoplasms; Female; Hirsutism; Humans; Hypoglycemic Agents; Menstruation Disturbances; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32794179
DOI: 10.1002/14651858.CD005552.pub3