scholarly journals Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews

2021 ◽  
Vol 12 ◽  
pp. 204209862198913
Author(s):  
Ryan Pelletier ◽  
Kelvin Ng ◽  
Wajd Alkabbani ◽  
Youssef Labib ◽  
Nicolas Mourad ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Systematic Reviews ◽  
Bone Fractures ◽  
Kidney Injury ◽  
Point Estimates ◽  
Increased Risk ◽  
Tract Infections

Background: Multiple published quantitative systematic reviews have reported on adverse events associated with the use of sodium glucose co-transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus. Aims: To summarize and appraise the quality of evidence from quantitative systematic reviews assessing adverse events of SGLT-2 inhibitors. Methods: We searched PubMed, EMBASE and the Cochrane Library for quantitative systematic reviews assessing SGLT-2 inhibitor safety. Two reviewers extracted data and assessed methodological quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool. Main outcomes included pooled and single study point estimaates (in the absence of pooled estimates) with corresponding 95% confidence intervals (CIs) of SGLT-2 inhibitors versus placebo or active comparators for genitourinary infections, volume depletion, acute kidney injury, bone fractures, diabetic ketoacidosis, lower limb amputations, cancers, and other notable adverse events. Results: Out of 1289 citations screened, 47 reviews assessed SGLT-2 inhibitor safety, of which 35 were of low quality. Canagliflozin, dapagliflozin and empagliflozin were consistently associated with an increased risk of genital tract infections versus placebo (point estimates ranged from 2.5 to 9.8) and other antihyperglycemic agents (point estimates ranged from 2.7 to 12.0). Canagliflozin and dapagliflozin were associated with an increased risk of diabetic ketoacidosis. Canagliflozin was the only agent associated with an increased amputation risk; however, this was driven by results from a single trial program. Dapagliflozin was the only agent that exhibited a statistically significant increased risk of urinary tract infections. Empagliflozin was associated with a statistically significant increased risk of bladder cancer; however, this finding was susceptible to detection bias. None of the agents were associated with a statistically significant increased risk of acute kidney injury, or bone fractures compared to placebo or mixed (active or placebo) comparators. Upper 95% CI limits do not rule out clinically meaningful outcomes. Conclusion: The majority of quantitative systematic reviews reporting on adverse events of SGLT-2 inhibitors were of low methodological quality. Despite almost 50 quantitative systematic reviews published on the safety of SGLT-2 inhibitors, clinicians are still left uncertain of the risks of important adverse effects. Plain Language Summary SGLT-2 iInhibitor side effects: overview of reviews Many published systematic reviews have reported on side effects associated with the use of sodium glucose co-transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes. We aimed to summarize and appraise the quality of evidence from quantitative systematic reviews assessing side effects of SGLT-2 inhibitors. Using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, two authors extracted data and assessed the methods of included reviews. Main outcomes included reported pooled and single study point estimates for several SGLT-2 inhibitor side effects such as genital infections, bone fractures, lower limb amputations, increased blood acidity, among others. Of the reviews included in our study, 35 of the 47 reviews assessed were of low quality. Canagliflozin and dapagliflozin were associated with an increased risk of blood acidity in a 2020 review. Canagliflozin was the only agent associated with an increased amputation risk; however, this was driven by results from a single trial program. Dapagliflozin was the only agent that exhibited a significantly increased risk of urinary tract infections. Empagliflozin was associated with an increased risk of bladder cancer; however, this finding was susceptible to bias. None of the agents were associated with an increased risk of kidney injury or bone fractures.

scholarly journals Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e022577 ◽  
Author(s):  
Jennifer R Donnan ◽  
Catherine A Grandy ◽  
Eugene Chibrikov ◽  
Carlo A Marra ◽  
Kris Aubrey-Bassler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bone Fractures ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Sglt2 Inhibitors ◽  
Current Evidence ◽  
Random Effects Models ◽  
Relative Risks ◽  
Increased Risk ◽  
Tract Infections

ObjectiveTo estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.DesignWe conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).InterventionSGLT2 inhibitors, compared with placebo or active comparators.Primary outcomesAcute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.ResultsWe screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.ConclusionsCurrent evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.PROSPERO registration numberCRD42016038715.

Proton Pump Inhibitors in 2021: Pros, Cons, and Everything in Between

2021 ◽  
pp. 263451612110217
Author(s):  
Joshua A. Sloan ◽  
Philip O. Katz
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Adverse Events ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Drug Class ◽  
Life Threatening

The medical and lay literature has exploded with reports of adverse events associated with proton pump inhibitors over the last 10 to 15 years. The dissemination of these reports to patients and clinicians have created substantial concerns regarding what has been an exceptionally valuable drug class, dramatically improving patient quality of life, and in many cases preventing life threatening side effects of other medication. Patients are more frequently seeking to avoid these medications, and practitioners are reducing or discontinuing them to the patient’s detriment due to a misunderstanding of the data. This review will discuss the data regarding the most commonly publicized adverse events and attempt to put them in perspective.

scholarly journals Potential of Beetroot and Blackcurrant Compounds to Improve Metabolic Syndrome Risk Factors

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 338
Author(s):  
Cameron Haswell ◽  
Ajmol Ali ◽  
Rachel Page ◽  
Roger Hurst ◽  
Kay Rutherfurd-Markwick
Keyword(s):  
Quality Of Life ◽  
Diabetes Mellitus ◽  
Risk Factors ◽  
Metabolic Syndrome ◽  
Metabolic Abnormalities ◽  
Dietary Nitrate ◽  
Increased Risk ◽  
High Concentrations

Metabolic syndrome (MetS) is a group of metabolic abnormalities, which together lead to increased risk of coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM), as well as reduced quality of life. Dietary nitrate, betalains and anthocyanins may improve risk factors for MetS and reduce the risk of development of CHD and T2DM. Beetroot is a rich source of dietary nitrate, and anthocyanins are present in high concentrations in blackcurrants. This narrative review considers the efficacy of beetroot and blackcurrant compounds as potential agents to improve MetS risk factors, which could lead to decreased risk of CHD and T2DM. Further research is needed to establish the mechanisms through which these outcomes may occur, and chronic supplementation studies in humans may corroborate promising findings from animal models and acute human trials.

Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

2018 ◽  
Vol 118 (11) ◽  
pp. 1930-1939
Author(s):  
Sebastian Göbel ◽  
Jürgen Prochaska ◽  
Lisa Eggebrecht ◽  
Ronja Schmitz ◽  
Claus Jünger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Vitamin K Antagonists ◽  
Plasma Concentrations ◽  
Regular Care ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
Specialized Care ◽  
The Impact

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

scholarly journals Clinical Practice of Hepatorenal Syndrome: A Brief Review on Diagnosis and Management

2021 ◽  
Vol 3 (2) ◽  
pp. 1-7
Author(s):  
. Rendy ◽  
. Febyan ◽  
Krisnhaliani Wetarini
Keyword(s):  
Clinical Practice ◽  
Hepatorenal Syndrome ◽  
Organ Transplant ◽  
Kidney Injury ◽  
Therapeutic Measures ◽  
Clinical Conditions ◽  
Underlying Pathophysiology

The hepatorenal syndrome is one of various potential causes of acute kidney injury in patients with decompensated liver disease. Hepatorenal syndrome is diagnosed based on reducing kidney function without any evidence of intrinsic kidney disease, including proteinuria, hematuria, or abnormal kidney ultrasonography. Clinically, hepatorenal syndrome is divided into two types named type 1 and type 2. The most favorable therapy for HRS cases is liver transplantation; however, only a few undergo this procedure due to the high mortality. Other modalities for hepatorenal syndrome therapy are pharmacology and non-pharmacology approaches. The purpose of management HRS is to optimize and stabilize the patient until an organ transplant available. This review aims to discuss the underlying pathophysiology and demonstrate the diagnostic approach of hepatorenal syndrome to determine the most appropriate therapeutic measures in clinical practice. The clinicians must be aware of management principles of hepatorenal syndrome to improve the quality of care for patients and optimize the clinical conditions.

scholarly journals Use of sodium-glucose cotransporter-2 inhibitors and urinary tract infections in type 2 diabetes patients: a systematic review

2019 ◽  
Vol 65 (2) ◽  
pp. 246-252 ◽  
Author(s):  
Izabela Rodrigues Figueiredo ◽  
Sara Cardoso Paes Rose ◽  
Nathália Bandeira Freire ◽  
Marina Stabile Patrocínio ◽  
Natália Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Randomized Clinical Trials ◽  
Oral Antidiabetic Agents ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Tract Infections

SUMMARY Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are drugs that act by maintaining glycosuria. Recent studies have shown promising effects of these in the treatment of type 2 diabetes mellitus (DM2). However, there may be an increased risk of developing urinary tract infections (UTIs) in patients treated with these. Our study aims to analyze the association between the risk of UTI in patients treated with SGLT2i. A systematic review of the literature was carried out by randomized clinical trials, totalizing at the end of the selection 23 articles that were statistically evaluated. The incidence of UTI was generally demonstrated in articles and in different subgroups: patients on SGLT2i monotherapy or on combination therapy; according to specific comorbidities of each sample or according to the drug used. They noticed an increase in the chance of UTI in the SGLT2i groups compared to the control groups on placebo or other oral antidiabetic agents. This increased chance was found predominantly with the use of Dapagliflozin, Canagliflozin, and Tofogliflozin, regardless of the dosing. Lastly, stands out that the dimension of UTI chances for DM2 patients who use SGLT2i remains to be more strictly determined.

scholarly journals An Overview of Systematic Reviews: Complementary Therapies for Cancer Patients

2019 ◽  
Vol 18 ◽  
pp. 153473541989002 ◽  
Author(s):  
Seong Min Lee ◽  
Ho Cheol Choi ◽  
Min Kyung Hyun
Keyword(s):  
Side Effects ◽  
Cancer Patients ◽  
Systematic Reviews ◽  
Complementary Therapies ◽  
The United States ◽  
Assessment Tools ◽  
Cochrane Library ◽  
Future Research ◽  
Cancer Type

Introduction: This article critically examines the systematic reviews (SR) and meta-analysis (MA) of complementary therapies for cancer patients to appraise the evidence level, and offers suggestions for future research and practice. Methods: The Cochrane Library and MEDLINE were searched from their inception to January 2018, to identify SR and MA of complementary therapies available for cancer patients. Final selected SR and MA were methodologically evaluated for their quality by applying the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR2) instrument. Data extraction and risk of quality assessments were performed by 2 independent reviewers. Results: A total of 104 studies were included in the analysis. The majority of the individual clinical trials included in the SR and MA were performed in China (48%) and the United States (26.9%). Breast cancer was the most studied cancer type (25%), and acupuncture was the most studied intervention (21%). Side effects of cancer such as pain, depression, and fatigue were effectively managed with complementary therapies. The methodologically problematic items included not listing the excluded studies and lack of protocol or protocol registration. Conclusions: With increasing interest in research, complementary therapies appear to be beneficial in reducing side effects and raising the quality of life of cancer patients. Complementary therapies have generally been studied for all cancers, with acupuncture being the most researched, regardless of the cancer type. Since AMSTAR2 is a stricter assessment tool than before, future studies need to consider the risk of methodological bias with caution and discuss appropriate overall quality assessment tools.

Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2

2019 ◽  
Vol 35 (5) ◽  
pp. 348-353 ◽  
Author(s):  
Grace Lewis ◽  
Amanda M. Morrill ◽  
Stephanie L. Conway-Allen ◽  
Bernard Kim
Keyword(s):  
Adverse Events ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Efficacy And Safety ◽  
Infantile Neuronal Ceroid Lipofuscinosis ◽  
Enzyme Replacement ◽  
Ceroid Lipofuscinosis ◽  
Tract Infections

The objective of this review is to summarize the pharmacology, efficacy, and safety of cerliponase alfa for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Cerliponase alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. A phase 1/2 trial established the efficacy and safety of cerliponase alfa for treatment of neuronal ceroid lipofuscinosis type 2. Treatment with intracerebroventricular cerliponase alfa resulted in slower decline of motor and language functions compared with natural history controls. Common adverse events include convulsions, electrocardiography abnormalities, pyrexia, vomiting, and upper respiratory tract infections. Intracerebroventricular device–related adverse events also occur. Cerliponase alfa is the first therapy for neuronal ceroid lipofuscinosis type 2 that targets the disease etiology. Cerliponase alfa is effective in delaying the progression of motor language decline for patients with neuronal ceroid lipofuscinosis type 2.

Incidence and prediction of checkpoint inhibitor immune-related nephrotoxicity.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 91-91
Author(s):  
Jonathan D Sorah ◽  
Tracy L. Rose ◽  
Roshni Radhakrishna ◽  
Vimal Derebail ◽  
Matthew I. Milowsky
Keyword(s):  
Autoimmune Disease ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Tumor Type ◽  
True Incidence ◽  
Platinum Based Chemotherapy ◽  
Increased Risk ◽  
Clinically Significant

91 Background: Immune checkpoint inhibitors (ICIs), through inhibition of self-tolerance, have the potential to cause immune-related adverse events that can affect any organ, including the kidneys. Our study aimed to better characterize the incidence of and predictive characteristics for immune-related nephrotoxicity. Methods: All patients at the University of North Carolina (UNC) who received ICIs between April 2014 and December 2018 for any malignancy were identified. Patients on dialysis or those who received concurrent platinum-based chemotherapy were excluded. Any patient who subsequently had a clinically significant acute kidney injury (AKI), defined as a doubling or more of baseline creatinine, was included for analysis. A retrospective chart review was performed to determine the cause of AKI. Any uncertain cases were reviewed by two nephrologists for expert consensus (R.R. and V.D.). Results: 1766 patients received an ICI during the study period. 123 (7%) patients had AKI within one year of the first ICI dose. 14 were due to immune-related nephrotoxicity (11% of patients with AKI and 0.8% of all ICI patients). Pre-existing autoimmune disease was more likely in patients with immune-related nephrotoxicity than in those with non-immune AKI (14% vs 3%, p = 0.04). Similarly, concurrent or prior other immune-related adverse events were more common in patients with immune-related AKI (57% vs 6%, p = 0.01). Patients with immune-related AKI were more likely to see a nephrologist (57% vs 23%, p = 0.007) and had a more profound increase in creatinine from baseline (median 2.6 vs 1.6, p = 0.02). Age, sex, urinalysis findings, and primary tumor type were not associated with increased risk. Conclusions: The true incidence of ICI related nephrotoxicity is difficult to ascertain due to the many confounders that contribute to AKI in this population. Severe immune-related nephrotoxicity is rare, but patients with preexisting autoimmune disease or history of immune-related adverse events are at increased risk.

Psylog, an EPA smartphone application to prevent antipsychotic side-effects

2014 ◽  
Vol 29 (S3) ◽  
pp. 672-673
Author(s):  
O. Andlauer ◽  
M. Rojnic-Kuzman
Keyword(s):  
Quality Of Life ◽  
Type 2 Diabetes ◽  
Side Effects ◽  
Psychiatric Care ◽  
Smartphone Application ◽  
Psychoeducational Intervention ◽  
Antipsychotic Medications ◽  
Antipsychotic Side Effects

Antipsychotic medications are used to treat a significant number of psychiatric disorders, such as schizophrenia or bipolar disorder, which have a significant impact on overall disability in Europe. Although these drugs have documented efficacy, they are also associated with side-effects such as drowsiness, weight gain, type 2 diabetes, or extrapyramidal symptoms [1]. These contribute to increasing overall morbidity and mortality [2], reduced quality of life, and can push patients to stop their medications. This often leads to relapse, and the need for a new hospital admission, which is detrimental to the patient, and create extra costs for the society. However, the monitoring of side-effects is rarely carried out in a standardized way in daily clinical practice. Smartphones are an acceptable and easy to use tool available to patients with schizophrenia [3]. The aim of the mPIVAS (mHealth psychoeducational intervention versus antipsychotic-induced side effects) project is to develop an effective and innovative smartphone application that can be used by psychiatrists and patients in order to monitor medications’ side-effects. The European Psychiatric Association (EPA) is involved in this project with the objective to develop this application in 6 languages. Part of the project includes training European early careers psychiatrists to the use Psylog and helping them to spread information about this new project in their own country, by organising local and national cascade courses. We expect an improvement in psychiatric care in all involved institutions through the education of employees, a better implication of patients in their disease, and an improved monitoring of antipsychotic side-effects.

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