-
La Medicina Del Lavoro Oct 2023Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In this systematic review and meta-analysis, we examined the association between PFAS exposure, particularly Perfluorooctanoic Acid (PFOA), and Perfluorooctane Sulfonic Acid (PFOS), and risk of kidney, liver, and testicular cancer.
METHODS
We systematically searched PubMed to identify cohort and case-control studies reported after the Monograph of the International Agency for Research on Cancer and the Toxicological Profile of the Agency for Toxic Substances and Disease Registry. We assessed the quality of the studies by using a modified version of the Newcastle-Ottawa Scale (NOS). Forest relative risk (RR) plots were constructed for liver, kidney, and testicular cancer. We conducted stratified analyses by geographic region, study design, quality score, outcome, years of publication, exposure source, and PFAS type. A random-effects model was used to address heterogeneity between studies.
RESULTS
Fifteen studies, including ten cohort studies, three case-control studies nested in a cohort, and two case-control studies were included after removing duplicate and irrelevant reports. We found an association between overall PFAS exposure and the risk of kidney cancers (RR=1.18, 95% CI =1.05-1.32; I =52.8%, 11 studies). Also, we showed an association between high-level exposure to PFAS and kidney cancer (RR=1.74, 95% CI =1.23-2.47; p=0.005) and testicular cancer (RR=2.22, 95% CI =1.12-4.39; p=0.057). There was no association with liver cancer. We found no heterogeneity by geographical region, PFAS type, study design, outcome, quality score, year of publication, or exposure source. Only two studies reported results among women.
CONCLUSIONS
We detected an association between overall PFAS exposure and kidney cancer and high doses of PFAS with testicular cancer. However, bias and confounding cannot be excluded, precluding a conclusion in terms of causality.
Topics: Female; Humans; Male; Testicular Neoplasms; Kidney; Liver; Kidney Neoplasms; Carcinoma, Renal Cell; Fluorocarbons
PubMed: 37878255
DOI: 10.23749/mdl.v114i5.15065 -
BMC Medicine Jul 2022Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.
METHODS
We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use.
RESULTS
We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08-1.24; HR 1.26, 95% CI 1.04-1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06-1.65; HR 1.61, 95% CI 0.97-2.67), and melanoma (OR 1.11, 95% CI 1.02-1.20; HR 1.03, 95% CI 0.93-1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43-4.57; HR 1.20, 95% CI 1.00-1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05-1.33), nodular (OR 1.23, 95% CI 1.08-1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08-1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.
CONCLUSIONS
Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.
TRIAL REGISTRATION
PROSPERO CRD42021234317 .
Topics: Bendroflumethiazide; Carcinoma, Squamous Cell; Humans; Hydrochlorothiazide; Indapamide; Melanoma; Skin Neoplasms; Thiazides
PubMed: 35794547
DOI: 10.1186/s12916-022-02419-9 -
Frontiers in Public Health 2023Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings.
RESULTS
The meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17).
CONCLUSION
We evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.
Topics: Humans; Alkanesulfonates; Fluorocarbons; Hypertension
PubMed: 37655293
DOI: 10.3389/fpubh.2023.1173101 -
The Cochrane Database of Systematic... Jun 2020Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins. Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.
MAIN RESULTS
Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.
AUTHORS' CONCLUSIONS
Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.
Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides
PubMed: 32557581
DOI: 10.1002/14651858.CD012735.pub2 -
Medicina (Kaunas, Lithuania) Dec 2022Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles... (Review)
Review
Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles of silodosin and tamsulosin for medical expulsive therapy (MET) of ureteral stones. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science to identify articles published before July 2022 that described randomized controlled trials comparing silodosin and tamsulosin for MET of ureteral stones. Endpoints were stone expulsion rate, stone expulsion time, and total complication rate. Results: In total, 14 studies were included in our analysis. The size of ureteral stones was <1 cm. Compared with tamsulosin, silodosin resulted in a significantly higher stone expulsion rate (p < 0.01, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.91 to 3.06, I2 = 0%) and significantly shorter stone expulsion time (p < 0.01, mean difference = −3.04, 95% CI = −4.46 to −1.63, I2 = 89%). The total complication rate did not significantly differ between silodosin and tamsulosin (p = 0.33, OR = 1.15, 95% CI = 0.87 to 1.52, I2 = 7%). Conclusions: Compared with tamsulosin, silodosin resulted in significantly better expulsion of ureteral stones <1 cm. The total complication rate did not significantly differ between silodosin and tamsulosin. Thus, silodosin may be superior to tamsulosin for MET of ureter stones <1 cm.
Topics: Humans; Tamsulosin; Ureteral Calculi; Adrenergic alpha-1 Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36556996
DOI: 10.3390/medicina58121794 -
BMC Infectious Diseases Sep 2023Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa.
METHODS
A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger's regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR).
RESULTS
Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88-4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61-1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13-1.35), male gender (AHR = 1.43, 95% CI: 1.22-1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34-3.23), anemia (AHR = 1.73, 95% CI: 1.34-2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08-2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08-2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3-0.77).
CONCLUSION
In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people.
Topics: Adult; Child; Male; Humans; Incidence; Isoniazid; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Africa South of the Sahara
PubMed: 37723415
DOI: 10.1186/s12879-023-08533-0 -
Rheumatology (Oxford, England) Dec 2023To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
OBJECTIVE
To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
METHODS
A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DUs. Randomized controlled trials (RCTs) and prospective longitudinal observational studies (OBSs) were eligible for inclusion. Data were extracted, applying the patient, intervention, comparison, outcome framework, and risk of bias (RoB) was assessed. Due to study heterogeneity, narrative summaries were used to present data.
RESULTS
Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1927 patients and 29 OBSs of 661 patients, at various RoB (total 2588 patients) showed that i.v. iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DUs. Bosentan reduced the rate of future DUs in two RCTs (moderate RoB) and eight OBSs at low to high RoB. Two small studies (moderate RoB) indicate that Janus kinase inhibitors may be effective for the treatment of active DUs, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DUs.
CONCLUSION
There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DUs. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DUs. The relatively low quality of evidence available has highlighted further areas of research need.
Topics: Adult; Humans; Skin Ulcer; Fingers; Scleroderma, Systemic; Bosentan
PubMed: 37335850
DOI: 10.1093/rheumatology/kead289 -
Annals of Palliative Medicine Feb 2022First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment of acne. However, due to its side effects, the clinical application of dapsone has not been promoted, and the value of the medication is still unclear. The aim of this study is to determine the efficacy and safety of dapsone gel in patients with acne.
METHODS
Systematic searches were performed using the following databases on January 4, 2020: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinoMed), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge Service Platform. A meta-analysis of randomized controlled trials was then conducted to analyze the efficacy and adverse events of dapsone gel treatment compared with excipient and other drug therapies. RevMan 5.3 software was used to calculate the odds ratio (OR), and the confidence interval (CI) was 95%.
RESULTS
Data of 11,424 participants across 7 trials which met the inclusion criteria were analyzed. Meta-analysis showed that dapsone gel alone or dapsone gel combined with isotretinoin was superior to excipient alone or oral isotretinoin alone in the treatment of acne (OR =1.51, 95% CI: 1.38-1.66, P<0.0001 random effects model, I2=0%). This indicates that dapsone gel is effective for the treatment of acne. We also found that dapsone gel is a more effective treatment for females (OR =1.80, 95% CI: 1.46-2.23). There was no significant difference in the incidence of adverse events between the dapsone group and the control group (OR =0.94, 95% CI: 0.82-1.14, P=0.24 random effects model; I2=29%). The common local adverse reactions in the dapsone group, such as dryness, heat, and eczema, were not statistically significant compared with those in the control group, and the side effects were transient.
DISCUSSION
Dapsone gel is effective in treating acne, and there is no significant difference in adverse events compared with other drugs.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Dapsone; Eczema; Female; Humans; Treatment Outcome; United States
PubMed: 35249339
DOI: 10.21037/apm-21-3935 -
Journal of the International AIDS... Jun 2023Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections... (Review)
Review
INTRODUCTION
Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.
METHODS
We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.
RESULTS
We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.
DISCUSSION
Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.
CONCLUSIONS
In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.
Topics: Infant; Female; Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Malaria; Uganda; Anti-Infective Agents; World Health Organization; Randomized Controlled Trials as Topic
PubMed: 37292018
DOI: 10.1002/jia2.26079 -
BMC Endocrine Disorders Oct 2022Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes.
METHODS
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs.
STUDY SELECTION
Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
OUTCOMES
The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia.
SYNTHESIS OF RESULTS
Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780).
RESULTS
Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.
CONCLUSION
Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
Topics: Adult; Humans; Adolescent; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glipizide; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemia; Glucagon-Like Peptide 1; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Symporters; Glucose; Sodium
PubMed: 36261824
DOI: 10.1186/s12902-022-01158-5