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American Journal of Epidemiology Aug 2021Evidence from observational studies may be considered complementary to that of randomized controlled trials (RCTs), particularly when assessing rare outcomes of drug... (Meta-Analysis)
Meta-Analysis
Evidence from observational studies may be considered complementary to that of randomized controlled trials (RCTs), particularly when assessing rare outcomes of drug therapies. Sodium/glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic agents that have been linked to an increased risk of diabetic ketoacidosis (DKA). We conducted a systematic review and separately meta-analyzed data from RCTs (n = 18; 2013-2019) and cohort studies (n = 7; 2017-2020) to assess the consistency of the magnitude of association between SGLT-2 inhibitors and DKA risk. We illustrate the strengths and weaknesses of the 2 designs. Results from RCTs and observational studies consistently showed almost a doubling in the risk of DKA among patients using an SGLT-2 inhibitor as compared with placebo or an active comparator. In a random-effects model, the pooled relative risk was 2.08 (95% confidence interval (CI): 1.28, 3.40) from placebo-controlled RCTs and 0.82 (95% CI: 0.25, 2.68) from active-comparator RCTs. The pooled adjusted hazard ratio from observational studies was 1.74 (95% CI: 1.28, 2.38). Notably, the 2 designs complement each other in several domains, including external and internal validity and power. This demonstrates a need for more comprehensive evidence when assessing rare adverse events for both sources.
Topics: Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Observational Studies as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33751032
DOI: 10.1093/aje/kwab052 -
Transplantation Reviews (Orlando, Fla.) Jan 2023Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is... (Review)
Review
Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review.
INTRODUCTION
Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus.
METHOD
We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated.
RESULTS
Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation.
CONCLUSIONS
While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Transplant Recipients; Glycated Hemoglobin; Retrospective Studies; Kidney Transplantation; Symporters; Glucose; Sodium
PubMed: 36427372
DOI: 10.1016/j.trre.2022.100729 -
Frontiers in Endocrinology 2021To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and...
Glycated Hemoglobin (HbA1c) Concentrations Among Children and Adolescents With Diabetes in Middle- and Low-Income Countries, 2010-2019: A Retrospective Chart Review and Systematic Review of Literature.
OBJECTIVES
To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and low-income countries, from 2010 to 2019.
METHODS
Retrospective data of children with DM from two hospital-based health records were reviewed. Data on HbA1c concentrations, hospitalization due to diabetic ketoacidosis, and patient demographics were collected and analyzed. A systematic review was subsequently performed to analyze publications that report HbA1c concentrations in patients aged <18 years. Patients' characteristics extracted from each publication were used to generate simulated individual data for pooled analysis. HbA1c estimates were derived from steady-state iterations.
RESULTS
Data of 843 diabetic children (aged 11.2 ± 3.9 years) with 2,658 HbA1c measures were retrieved from the two hospitals during the period 2010-2020. The duration of diabetes in the patients was 4.4 ± 2.8 years, and their HbA1c was 8.1 ± 2.2%. Patients who were internal migrants had significantly higher HbA1c concentration than resident patients (8.4 7.9%). The literature review yielded 1,164 publications, and the majority (74.1%) of patient data were published in high-income countries. The patient data extracted from these publications generated 486,416 HbA1c concentration estimates between 2005 and 2019. The average HbA1c concentration during the 15 years was 9.07 ± 2.15%. The mean HbA1c concentrations among children were 8.23, 8.73, 9.20, and 10.11% in high-income country (HIC), upper-middle income country (UMIC), lower-middle income country (LMIC), and low-income country (LIC) respectively. The mean rate of optimized glycemic control (HbA1c <7.5%) among children was 32.4, 27.5, 21.7, and 12.7% in HIC, UMIC, LMIC, and LIC, respectively.
CONCLUSIONS
The current study indicated that there is substantial room for improvement in glycemic control in children with DM worldwide, especially in middle- and low-income countries.
Topics: Adolescent; Child; Child, Preschool; China; Data Collection; Diabetes Mellitus; Diabetic Ketoacidosis; Electronic Health Records; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Infant; Infant, Newborn; Male; Models, Statistical; Retrospective Studies
PubMed: 33912137
DOI: 10.3389/fendo.2021.651589 -
Heart Failure Reviews Jan 2024Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection... (Meta-Analysis)
Meta-Analysis Review
Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.
Topics: Humans; Stroke Volume; Diabetic Ketoacidosis; Hyperkalemia; Hypokalemia; Heart Failure; Hypoglycemia; Acute Kidney Injury; Fractures, Bone; Glucose
PubMed: 37917192
DOI: 10.1007/s10741-023-10363-w -
Diabetology International Oct 2021COVID-19 is associated with diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and euglycaemic DKA (EDKA); however, evidence regarding parameters...
AIMS
COVID-19 is associated with diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and euglycaemic DKA (EDKA); however, evidence regarding parameters affecting outcome and mortality rates is scarce.
METHODS
A systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 2020 to 7 January 2021 to identify all studies describing clinical profile, outcome and mortality rates regarding DKA, HHS, DKA/HHS and EDKA cases in COVID-19 patients. The appropriate Joanna Briggs Institute tools were used for quality assessment; quality of evidence was approached using GRADE. Univariate and multivariate analyses were used to assess correlations between clinical characteristics and outcome based on case reports. Combined mortality rates (CMR) were estimated from data reported in case report series, cross-sectional studies, and meta-analyses. The protocol was submitted to PROSPERO (ID: 229356/230737).
RESULTS
From 312 identified publications, 44 were qualitatively and quantitatively analyzed. Critical COVID-19 necessitating ICU ( = 3 × 10), DKA/HHS presence ( = 0.021), and AKI ( = 0.037) were independently correlated with death. Increased COVID-19 severity ( = 0.003), elevated lactates ( < 0.001), augmented anion gap ( < 0.001), and AKI ( = 0.002) were associated with DKA/HHS. SGLT-2i were linked with EDKA ( = 0.004) and negatively associated with AKI ( = 0.023). CMR was 27.1% (95% CI 11.2-46.9%) with considerable heterogeneity ( = 67%).
CONCLUSION
Acute diabetes-related metabolic emergencies in COVID-19 patients lead to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Previous SGLT-2i treatment, though associated with EDKA, might preserve renal function in COVID-19 patients.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13340-021-00502-9.
PubMed: 33777611
DOI: 10.1007/s13340-021-00502-9 -
Frontiers in Public Health 2023Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered...
OBJECTIVE
Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered diabetes is insulin, but a detailed therapeutic method has not yet been established. To prevent severe symptoms and mortality of diabetic ketoacidosis in advanced-stage cancer patients, the establishment of effective treatment of CPI-triggered diabetes, other than insulin therapy, is required.
METHODS
We present a case of a 76-year-old man with CPI-triggered diabetes who was treated with nivolumab and ipilimumab for lung cancer. We also conducted a systematic review of 48 case reports of type 1 diabetes associated with nivolumab and ipilimumab therapy before June 2023.
RESULTS
The patient's hyperglycemia was not sufficiently controlled by insulin therapy, and after the remission of ketoacidosis, the addition of a sodium-glucose transporter (SGLT) 2 inhibitor, dapagliflozin, improved glycemic control. Most of the reported nivolumab/ipilimumab-induced type 1 diabetes was treatable with insulin, but very few cases required additional oral anti-diabetic agents to obtain good glucose control.
CONCLUSION
Although SGLT2 inhibitors have been reported to have adverse effects on ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPI-triggered diabetes, SGLT2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient's ketoacidosis.
Topics: Male; Humans; Aged; Nivolumab; Sodium-Glucose Transporter 2 Inhibitors; Ipilimumab; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Insulin; Lung Neoplasms
PubMed: 38106883
DOI: 10.3389/fpubh.2023.1264056 -
Medicine Aug 2020To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM).
METHODS
Through April 2019, the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure databases were electronically searched to identify randomized controlled trials exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluations of the obtained literature were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using Revman 5.3 software.
RESULTS
A total of 7 randomized controlled trials were included. The meta-analysis results showed that compared with the patients in the placebo group, the patients in the SOTA group had a lower hemoglobin A1c (mean difference [MD] = -0.28, 95% confidence interval [CI] [-0.34, -0.22], P < .01), lower total daily insulin use (MD = -8.89, 95% CI [-11.64, -6.13], P < .01), faster weight loss (MD = -3.03, 95% CI [-3.79, -2.26], P < .01), better fasting blood glucose and 2-hour postprandial blood glucose control (MD = -0.75, 95% CI [-1.04, -0.45], P < .01; MD = -2.42, 95% CI [-3.17, -1.67], P < .01), and a higher rate of well-controlled glucose levels (relative risk = 1.75, 95% CI [1.55, 1.99], P < .01), while no significant difference in the incidence of severe hypoglycemic events was found between the SOTA and placebo groups (risk difference [RD] = -0.01, 95% CI [-0.02, 0.00], P = .13). The incidence of diabetic ketoacidosis was higher in the SOTA group than in the placebo group (RD = 0.03, 95% CI [0.02, 0.04], P < .01). The incidence of genital mycotic infection was higher in the SOTA group than in the placebo group (RD = 0.06, 95% CI [0.05, 0.08], P < .01). No significant difference in the incidence of urinary tract infections was detected between the SOTA group and the placebo group (RD = 0.00, 95% CI [-0.01, 0.01], P = 0.97).
CONCLUSIONS
SOTA is a potential drug for the treatment of T1DM and is effective for controlling blood sugar. The main adverse reactions to SOTA are genital mycotic infections and diabetic ketoacidosis. We must further assess the severity of diabetic ketoacidosis caused by SOTA.
Topics: Chemotherapy, Adjuvant; Diabetes Mellitus, Type 1; Glycosides; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 1
PubMed: 32871972
DOI: 10.1097/MD.0000000000020875 -
Diabetes, Obesity & Metabolism Mar 2021To assess the efficacy and safety of glucose-lowering drugs used as an adjunct to insulin therapy in adults with type 1 diabetes. (Meta-Analysis)
Meta-Analysis
AIM
To assess the efficacy and safety of glucose-lowering drugs used as an adjunct to insulin therapy in adults with type 1 diabetes.
METHODS
We searched Medline, Embase and the Cochrane Central Register of Controlled Trials up to 24 January 2020 for randomized controlled trials. Our primary outcome was change in HbA1c. We additionally assessed eight efficacy and six safety secondary endpoints. We performed random effects frequentist network meta-analysis to estimate mean differences (MDs) and odds ratios (ORs), alongside 95% confidence intervals (CIs). We assessed risk of bias and evaluated confidence in the evidence for the primary outcome.
RESULTS
We included 58 trials comprising 13 216 participants. Overall, sodium-glucose co-transporter (SGLT) inhibitors, liraglutide, glibenclamide, acarbose and metformin reduced HbA1c compared with placebo (MDs ranging from -0.46% [95% CI -0.64% to -0.29%] for empagliflozin to -0.20% [-0.35% to -0.06%] for metformin). SGLT inhibitors, exenatide daily, liraglutide and metformin reduced body weight and total daily insulin dose, while liraglutide and SGLT inhibitors reduced blood pressure. Diabetic ketoacidosis and genital infections were more frequent with SGLT inhibitors, while exenatide, liraglutide, pramlintide and metformin increased the incidence of nausea. No drug increased the incidence of severe hypoglycaemia. Confidence in evidence was mainly moderate to very low.
CONCLUSIONS
Specific drugs may improve glycaemic control and reduce body weight, blood pressure and total daily insulin dose in patients with type 1 diabetes. However, low quality of evidence and an increased risk of diabetic ketoacidosis, genital infections or gastrointestinal adverse events should be taken into consideration by healthcare providers and patients. Future long-term trials are needed to clarify their benefit-to-risk profile and elucidate their role in clinical practice.
Topics: Adult; Diabetes Mellitus, Type 1; Glucose; Humans; Hypoglycemic Agents; Network Meta-Analysis; Pharmaceutical Preparations; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33300282
DOI: 10.1111/dom.14291 -
Diabetes Research and Clinical Practice May 2021To determine if diabetes awareness campaigns are an effective intervention to reduce diabetes ketoacidosis at diagnosis of type 1 diabetes in children and youth. (Meta-Analysis)
Meta-Analysis
AIM
To determine if diabetes awareness campaigns are an effective intervention to reduce diabetes ketoacidosis at diagnosis of type 1 diabetes in children and youth.
METHODS
Search strategies included PubMed, Scopus, CINAHL and WOS electronic databases, hand search of select journals and a grey literature search "Google" search to include all relevant information. Studies included community-based interventions focused on children younger than 18 years old. The difference in the frequency of DKA was measured in two separate comparisons; before and after perform awareness campaigns in the same area, and between areas with and without intervention campaigns.
RESULTS
Of 1136 records identified, 14 studies were eligible for the analysis. The first group of 12 studies measured DKA at diagnosis, before (n = 6548 individuals) and after (n = 4931 individuals) the awareness campaigns. The pooled difference was a reduction of 7.20% (95%CI: 0.99-13.41). The second group of four studies measured the difference in an area with no intervention (n = 338 individuals) and in an area with an awareness campaign (n = 187 individuals). The pooled difference in DKA was 35.71% (95%CI: 5.81-65.61).
CONCLUSIONS
This review demonstrated that DKA awareness campaigns are effective to reduce DKA among children and adolescents with type 1 diabetes and the core components that explain why these campaigns are effective. Back to top.
Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Male
PubMed: 33901625
DOI: 10.1016/j.diabres.2021.108838 -
Clinical Therapeutics Aug 2020Insulin analogues (IAs) are the mainstay for the management of diabetic ketoacidosis (DKA). However, the relative efficacy of newer IAs is uncertain. The aim of this... (Meta-Analysis)
Meta-Analysis
PURPOSE
Insulin analogues (IAs) are the mainstay for the management of diabetic ketoacidosis (DKA). However, the relative efficacy of newer IAs is uncertain. The aim of this study was to compare the relative efficacy and safety of IAs for the management of DKA using an indirect treatment comparison (ITC).
METHODS
PubMed, EMBASE, Scopus, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing short-, rapid-, and long-acting IAs in patients with DKA. The primary outcomes of interest were time taken to normalize DKA and time taken to normalize blood glucose levels. The secondary outcomes of interest were the amount of insulin needed to normalize DKA, the length of hospital stay, and the number of hypoglycemic events in the intervention and comparator groups. Bayesian ITC was performed by using the gemtc package in the R program. Continuous outcomes are reported as mean difference (MD), and binary outcomes are reported as odds ratios (ORs), with 95% credible intervals (CrIs). The Cochrane risk of bias tool was used to assess the risk of bias in the included RCTs.
FINDINGS
Ten RCTs randomizing 435 participants to treatment were included in this ITC. A total of 5 interventions (lispro, glargine with regular insulin [RI], glulisine, aspart, and regular insulin) were compared for both safety and efficacy outcomes in DKA. Glargine co-administered with regular insulin showed superiority for clinical outcomes compared with regular insulin: consuming less time (MD, -3.1 h; 95% CrI, -7.9 to 1.8), amount of insulin required (MD, -32 U; 95% CrI, 83.0 to 18.0), and the length of hospitalization (MD, -0.82 day; 95% CrI, -2.7 to 1.0) to normalize DKA. However, these results were not statistically significant. Insulin aspart had fewer reports of hypoglycemic events (OR, 1.7; 95% CrI, 0.34 to 9.3) than regular insulin.
IMPLICATIONS
Newer IAs were found to be equally effective and safe as regular insulin in the treatment of DKA. Thus, administering these IAs can be considered a safe and cost-effective alternative for DKA management in non-ICU settings. Cost-effective analysis of the newer IAs is needed because these agents are expensive compared with regular insulin.
Topics: Bayes Theorem; Blood Glucose; Diabetic Ketoacidosis; Humans; Hypoglycemia; Hypoglycemic Agents; Insulins; Length of Stay; Randomized Controlled Trials as Topic
PubMed: 32798057
DOI: 10.1016/j.clinthera.2020.06.017