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Journal of the American Pharmacists... 2024The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported.
OBJECTIVE
This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents.
METHODS
A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software.
RESULTS
Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables.
CONCLUSIONS
Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Prevalence; Sodium-Glucose Transporter 2; Nimustine; Diabetes Mellitus, Type 2; Hypoglycemic Agents
PubMed: 37844733
DOI: 10.1016/j.japh.2023.10.010 -
Turkish Journal of Emergency Medicine 2023The first-line treatment of diabetes ketoacidosis (DKA) involves fluid resuscitation with normal saline infusion to correct hypovolemia. Hyperchloremic metabolic... (Review)
Review
The first-line treatment of diabetes ketoacidosis (DKA) involves fluid resuscitation with normal saline infusion to correct hypovolemia. Hyperchloremic metabolic acidosis from aggressive normal saline administration was associated with worse clinical outcomes in managing DKA. Other choices for normal saline include balanced electrolyte solutions (BESs). This study aimed to compare the clinical effects between BESs and normal saline in managing DKA. This study was a systematic review of probing articles published from inception to October 2021 in Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Google Scholar, and Scopus. Eight randomized controlled trials with a total of 595 individuals were included. The data were analyzed at 95% confidence level using random-effects models. For the primary outcomes, there was no difference in the duration of DKA resolution. (Mean difference [MD] -4.73, 95% confidence interval [CI] -2.72-4.92; = 92%; = 0.180). However, there was a significantly lower postresuscitation chloride concentration in the BES (MD 2.96 95% CI - 4.86 to - 1.06; = 59%; = 0.002). For the secondary outcomes, there was a significant reduction in duration for normalization of bicarbonate in the BES group (MD 3.11 95% CI - 3.98-2.23; = 5%; = 0.0004). There were no significant differences between groups in duration for recovery of pH, intensive unit admission, and adverse events (mortality and acute renal failure). Resuscitation with BES was associated with decreased chloride and increased bicarbonate values in DKA patients. It suggests that BES prevents DKA patients from hyperchloremic metabolic acidosis.
PubMed: 37529790
DOI: 10.4103/tjem.tjem_355_22 -
BMJ Open Feb 2024This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in Ethiopia.
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Age 15 and above all patients with diabetes with the diagnosis of DKA in Ethiopia DATA SOURCE: PubMed/MEDLINE, Cochrane Library, Science Direct, HINARI, Google Scholar and grey literatures were accessed to find relevant articles. Studies that have been conducted and reported in English language, articles with an available full-text, and observational studies were included. The task of searching sources was carried out from all stated electronic databases performed during 15 April-29 April 2023.
PRIMARY AND SECONDARY OUTCOME MEASURES
Eligible studies were critically appraised by three independent reviewers for methodological quality in the review using standardised critical appraisal instruments from Joanna Briggs Institute (JBI) for observational studies. After the finally extracted studies were exported, systematic review and meta-analysis were conducted using Unified Management, Assessment and Review of Information (JBI SUMARI) (JBI, Adelaide, Australia) and STATA V.17 software. Sensitivity tests were done, and funnel plot inspections with Egger's test were used to check for publication bias.
RESULT
From a total of 19 studies with 6498 study participants, the pooled prevalence of DKA among patients with DM in Ethiopia was 30.92% (95% CI 29.96 to 31.89) with a significant statistical heterogeneity (I=99.2, p=<0.001). Sensitivity analysis suggested that three studies showed deviations from the estimated pooled prevalence. A funnel plot inspection and Egger's test indicated the absence of a publication bias.
CONCLUSION
This systematic review and meta-analysis revealed that the prevalence of DKA among patients with DM in Ethiopia was 30.92%. Besides, different behavioural and clinical determinants of DKA among patients with DM were identified. However, further studies should be conducted, particularly on the possible determinants of DKA, and different stakeholders should be engaged to minimise its burden.
Topics: Humans; Adolescent; Diabetic Ketoacidosis; Ethiopia; Prevalence; Databases, Factual; Australia; Diabetes Mellitus
PubMed: 38341216
DOI: 10.1136/bmjopen-2023-077151 -
Frontiers in Endocrinology 2023The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUNDS
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
METHODS
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
RESULTS
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
CONCLUSION
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fractures, Bone; Hypoglycemia; Hypovolemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37701900
DOI: 10.3389/fendo.2023.1238399 -
Cureus Apr 2024As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available... (Review)
Review
As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available that target tumor cells in innovative ways. Immunotherapies (e.g., immune checkpoint inhibitors (ICI)) ramp up the immune system to target cancer cells, providing patients with more personalized and tumor cell-specific treatment options. This new age oncological treatment option has been found to provide a more meaningful and stronger alternative to traditional chemotherapy, resulting in longer periods of remission and milder side effects. However, because ICI heightens the immune system, resultant autoimmune conditions can occur. One of the most recently shown adverse effects of ICI are extreme hyperglycemia (i.e., type 1 diabetes) and diabetic ketoacidosis (DKA). To determine the incidence of immunotherapy-induced diabetes, a systematic literature review was performed using CINHAL, EBSCO, MEDLINE, and Web of Science. A total of 403 articles were initially screened, with a final 28 case reports included. The results show that checkpoint inhibitors were found to be most commonly associated with new-onset diabetes as opposed to traditional chemotherapy. Additionally, 41% of patients developed autoimmune diabetes and DKA after being placed on a single therapy of pembrolizumab (targets PD-1: programmed cell death protein 1). However, the pathological process underlying the development of endocrinopathies after treatment with ICI continues to be under investigation.
PubMed: 38606021
DOI: 10.7759/cureus.57894 -
Frontiers in Endocrinology 2022Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs-... (Review)
Review
Combined diabetic ketoacidosis and hyperosmolar hyperglycemic state in type 1 diabetes mellitus induced by immune checkpoint inhibitors: Underrecognized and underreported emergency in ICIs-DM.
BACKGROUND
Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs- diabetes mellitus (DM) cases and is always ignored by physicians. This study aimed to conduct a systematic review to recognize better the rare adverse event of combined DKA-HHS associated with immune checkpoints.
METHODS
A electronic search in Pubmed/Cochrane/Web of Science, complemented by manual searches in article references, was conducted to identify clinical features of ICIs-combined DKA-HHS.
RESULTS
we identified 106 patients with ICIs- type 1 diabetes mellitus (T1DM) from 82 publications: 9 patients presented a coexistence of metabolic acidosis, severe hyperglycemia, and/or DKA; All patients were not diagnosed as combined DKA-HHS. Compared with ICIs-DKA patients, combined DKA-HHS cases were prone to higher hyperglycemia (1020 ± 102.5 vs 686.7 ± 252.6mg/dL). Moreover, acute kidney injury (87.5% vs 28.6%) and prior chemotherapy (66.7% vs 31.6%) showed higher occurrences with the onset of ICIs-HHS or combined DKA-HHS.B.
CONCLUSIONS
Combined DKA-HHS portends a poor diagnosis in patients with coexistence features of DKA and HHS, which healthcare professionals and patients should be aware of due to differences in treatment. Our observational retrospective case series shows that patients with more risk factors were more likely to develop combined DKA-HHS. We are the first to report this group of patients' clinical characteristics and outcomes.
Topics: Humans; Diabetic Ketoacidosis; Hyperglycemic Hyperosmolar Nonketotic Coma; Diabetes Mellitus, Type 1; Immune Checkpoint Inhibitors; Retrospective Studies; Hyperglycemia
PubMed: 36686495
DOI: 10.3389/fendo.2022.1084441 -
International Journal of Clinical... Mar 2016Diabetic ketoacidosis (DKA) is an acute and risky complication of type 1 diabetes. The aim of this study is to build the overall rate of DKA in Arab patients with type 1... (Review)
Review
AIMS
Diabetic ketoacidosis (DKA) is an acute and risky complication of type 1 diabetes. The aim of this study is to build the overall rate of DKA in Arab patients with type 1 diabetes in the 22 Arab nations. This is expected to tailor the healthcare approaches in Arab countries where attention is needed to save lives from the devastating consequences of DKA.
METHODS
The study here is a quantitative analysis of the articles indexed in four different scientific literature databases: Web of Science, PubMed, Science Direct and Scopus, from inception to June 2015. Arab patients with type 1 diabetes who presented with DKA have been captured. Key information was possible to extract for patients belong to only 12 Arab countries out of the 22 Arab patients.
RESULTS
Twenty-nine studies in 12 different Arab countries captured 4,688 type 1 diabetes patients with overall rates of 46.7% patients presented with DKA, ranging from a low of 17% in Egypt to a high of 100% in Morocco, Algeria and Tunisia.
CONCLUSION
This is the first descriptive quantitative study to determine the overall DKA rate in 46 years of studies in the Arab world of patients with type 1 diabetes; DKA rates were found to range from 17% to 100% with overall rate of 46.7%.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Middle East; Prevalence; Risk Factors; Young Adult
PubMed: 26842462
DOI: 10.1111/ijcp.12777 -
Pediatrics Sep 2014We sought to create and implement recommendations from an evidence-based pathway for hospital management of pediatric diabetic ketoacidosis (DKA) and to sustain... (Review)
Review
OBJECTIVE
We sought to create and implement recommendations from an evidence-based pathway for hospital management of pediatric diabetic ketoacidosis (DKA) and to sustain improvement. We hypothesized that development and utilization of standard work for inpatient care of DKA would lead to reduction in hypokalemia and improvement in outcome measures.
METHODS
Development involved systematic review of published literature by a multidisciplinary team. Implementation included multidisciplinary feedback, hospital-wide education, daily team huddles, and development of computer decision support and electronic order sets.
RESULTS
Pathway-based order sets forced clinical pathway adherence; yet, variations in care persisted, requiring ongoing iterative review and pathway tool adjustment. Quality improvement measures have identified barriers and informed subsequent adjustments to interventions. We compared 281 patients treated postimplementation with 172 treated preimplementation. Our most notable findings included the following: (1) monitoring of serum potassium concentrations identified unanticipated hypokalemia episodes, not recognized before standard work implementation, and earlier addition of potassium to fluids resulted in a notable reduction in hypokalemia; (2) improvements in insulin infusion management were associated with reduced duration of ICU stay; and (3) with overall improved DKA management and education, cerebral edema occurrence and bicarbonate use were reduced. We continue to convene quarterly meetings, review cases, and process ongoing issues with system-based elements of implementing the recommendations.
CONCLUSIONS
Our multidisciplinary development and implementation of an evidence-based pathway for DKA have led to overall improvements in care. We continue to monitor quality improvement metric measures to sustain clinical gains while continuing to identify iterative improvement opportunities.
Topics: Diabetic Ketoacidosis; Disease Management; Hospitalization; Humans; Patient Care
PubMed: 25092935
DOI: 10.1542/peds.2013-3764 -
JAMA Pediatrics Dec 2022Presenting with diabetic ketoacidosis (DKA) at onset of type 1 diabetes (T1D) remains a risk. Following a 2011 systematic review, considerable additional articles have...
IMPORTANCE
Presenting with diabetic ketoacidosis (DKA) at onset of type 1 diabetes (T1D) remains a risk. Following a 2011 systematic review, considerable additional articles have been published, and the review required updating.
OBJECTIVE
To evaluate factors associated with DKA at the onset of T1D among pediatric patients.
EVIDENCE REVIEW
In this systematic review, PubMed, Embase, Scopus, CINAHL, Web of Science, and article reference lists were searched using the population, intervention, comparison, outcome search strategy for primary research studies on DKA and T1D onset among individuals younger than 18 years that were published from January 2011 to November 2021. These studies were combined with a 2011 systematic review on the same topic. Data were pooled using a random-effects model.
FINDINGS
A total of 2565 articles were identified; 149 were included, along with 46 from the previous review (total 195 articles). Thirty-eight factors were identified and examined for their association with DKA at T1D onset. Factors associated with increased risk of DKA were younger age at T1D onset (<2 years vs ≥2 years; odds ratio [OR], 3.51; 95% CI, 2.85-4.32; P < .001), belonging to an ethnic minority population (OR, 0.40; 95% CI, 0.21-0.74; P = .004), and family history of T1D (OR, 0.46; 95% CI, 0.37-0.57; P < .001), consistent with the 2011 systematic review. Some factors that were not associated with DKA in the 2011 systematic review were associated with DKA in the present review (eg, delayed diagnosis: OR, 2.27; 95% CI, 1.72-3.01; P < .001). Additional factors associated with risk of DKA among patients with new-onset T1D included participation in screening programs (OR, 0.35; 95% CI, 0.21-0.59; P < .001) and presentation during the COVID-19 pandemic (OR, 2.32; 95% CI, 1.76-3.06; P < .001).
CONCLUSIONS AND RELEVANCE
In this study, age younger than 2 years at T1D onset, belonging to an ethnic minority population, delayed diagnosis or misdiagnosis, and presenting during the COVID-19 pandemic were associated with increased risk of DKA. Factors associated with decreased risk of DKA included greater knowledge of key signs or symptoms of DKA, such as a family history of T1D or participation in screening programs. Future work should focus on identifying and implementing strategies related to these factors to reduce risk of DKA among new patients with T1D.
Topics: Child; Humans; Child, Preschool; Diabetic Ketoacidosis; Diabetes Mellitus, Type 1; Ethnicity; COVID-19; Pandemics; Minority Groups
PubMed: 36215053
DOI: 10.1001/jamapediatrics.2022.3586 -
World Journal of Clinical Cases Aug 2023Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below...
BACKGROUND
Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population.
AIM
To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.
METHODS
We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings.
RESULTS
Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments.
CONCLUSION
Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.
PubMed: 37727728
DOI: 10.12998/wjcc.v11.i24.5700