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Frontiers in Pharmacology 2023Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). However,...
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the risk of diabetic ketoacidosis (DKA) in patients remains unclear. The purpose of this study is to conduct this systematic review and network meta-analysis for the risk of DKA of SGLT2 inhibitors in patients with T2DM. We searched for randomized controlled trials (RCTs) concerning SGLT2 inhibitors in patients with T2DM in PubMed, EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov from inception to January 2022. The primary outcomes were the risk of DKA. We assessed the sparse network with a fixed-effect model and consistency model in a frequentist framework with a graph-theoretical method by the netmeta package in R. We assessed the evidence quality of evidence of outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). In total, 36 studies involving 52,264 patients were included. The network showed that there was no significant difference observed among SGLT2 inhibitors, other active antidiabetic drugs, and placebo in the risk of DKA. There was no significant difference in the DKA risk between different doses of SGLT2 inhibitors. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and P-score showed that compared to placebo, SGLT2 inhibitors might increase the risk of DKA (P-score = 0.5298). Canagliflozin might have a higher DKA risk than other SGLT2 inhibitors (P-score = 0.7388). Neither SGLT2 inhibitors nor other active antidiabetic drugs were associated with an increased risk of DKA compared to placebo, and the risk of DKA with SGLT2 inhibitors was not found to be dose-dependent. In addition, the use of canagliflozin was less advisable than other SGLT2 inhibitors according to the rankings and P-score. https://www.crd.york.ac.uk/prospero/, identifier PROSPERO, CRD42021297081.
PubMed: 37397500
DOI: 10.3389/fphar.2023.1145587 -
British Journal of Anaesthesia Jul 2019Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with...
BACKGROUND
Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Guidelines are still evolving concerning the perioperative management of patients on SGLT2i. We performed a systematic review of published reports of DKA from SGLT2i in the surgical setting to understand better the clinical presentation and characteristics of SGLT2i-associated DKA.
METHODS
We searched PubMed, Embase, and ProQuest for reports of perioperative DKA involving SGLT2i up to January 2019.
RESULTS
Forty-two reports of EDKA and five cases of hyperglycaemic diabetic ketoacidosis (HDKA) were identified from 33 publications. Canagliflozin was implicated in 26 cases. Presentation time varied from a few hours up to 6 weeks after operation. Precipitating factors may include diabetes medication changes, diet modifications, and intercurrent illnesses. There were 13 cases (12 EDKA and one HDKA) of bariatric surgery, 10 of them noted very-low-calorie diet regimes as a precipitating factor. No precise association between interruption of SGLT2i and the occurrence of DKA could be identified. Seven patients required mechanical ventilation, and acute kidney injury was noted in five. Five cases needed imaging to rule out anastomotic leak and pulmonary embolism, all of them revealed negative findings. Outcome data were available in 32 cases, all of them recovered completely.
CONCLUSIONS
EDKA is likely to be under-recognised because of its atypical presentation and may delay the diagnosis. Understanding this clinical entity, vigilance towards monitoring plasma/capillary ketones helps in early identification and assists in the management.
Topics: Diabetic Ketoacidosis; Humans; Intraoperative Complications; Postoperative Complications; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31060732
DOI: 10.1016/j.bja.2019.03.028 -
Critical Care Explorations Feb 2023In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the... (Review)
Review
UNLABELLED
In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the efficacy and safety of different insulin infusion doses for the treatment of pediatric DKA.
DATA SOURCES
We searched MEDLINE, EMBASE, PubMed, and Cochrane from inception to April 1, 2022.
STUDY SELECTION
We included randomized controlled trials (RCTs) of children with DKA comparing intravenous insulin infusion administered at 0.05 units/kg/hr (low dose) versus 0.1 units/kg/hr (standard dose).
DATA EXTRACTION
We extracted data independently and in duplicate and pooled using a random effects model. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach.
DATA SYNTHESIS
We included four RCTs ( = 190 participants). In children with DKA, low-dose compared with standard-dose insulin infusion probably has no effect on time to resolution of hyperglycemia (mean difference [MD], 0.22 hr fewer; 95% CI, 1.19 hr fewer to 0.75 hr more; moderate certainty), or time to resolution of acidosis (MD, 0.61 hr more; 95% CI, 1.81 hr fewer to 3.02 hr more; moderate certainty). Low-dose insulin infusion probably decreases the incidence of hypokalemia (relative risk [RR], 0.65; 95% CI, 0.47-0.89; moderate certainty) and hypoglycemia (RR, 0.37; 95% CI, 0.15-0.80; moderate certainty), but may have no effect on rate of change of blood glucose (MD, 0.42 mmol/L/hr slower; 95% CI, 1 mmol/L/hr slower to 0.18 mmol/L/hr faster; low certainty).
CONCLUSIONS
In children with DKA, the use of low-dose insulin infusion is probably as efficacious as standard-dose insulin, and probably reduces treatment-related adverse events. Imprecision limited the certainty in the outcomes of interest, and the generalizability of the results is limited by all studies being performed in a single country.
PubMed: 36844374
DOI: 10.1097/CCE.0000000000000857 -
Frontiers in Endocrinology 2022Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1 diabetes. This systematic review and meta-analysis aimed to estimate the risk of DKA, including severe DKA, during the COVID-19 pandemic versus the prior-to-COVID-19 period among pediatric patients with type 1 diabetes.
METHODS
PubMed and EMBASE were searched for observational studies investigating the risk of DKA among pediatric patients with type 1 diabetes during the COVID-19 pandemic and the prior-to-COVID-19 period. A random meta-analysis model was performed to estimate the relative risk of DKA during the COVID-19 pandemic compared to before the pandemic. Subgroup analyses were conducted based on the type 1 diabetes status, established or newly diagnosed. In addition, sensitivity analysis was conducted for studies that reported results from adjusted analysis for potential confounders using fixed effect model.
RESULTS
A total of 20 observational studies reported the risk of DKA, of which 18 reported the risk of severe DKA. The risks of DKA and severe DKA were 35% (RR 1.35, 95%CI 1.2-1.53, = 71%) and 76% (RR 1.76, 95%CI 1.33-2.33, 44%) higher in the during-COVID-19 group compared to the prior-to-COVID-19 group, respectively. Among patients with newly diagnosed type 1 diabetes, the risk of DKA was 44% higher for the during-COVID-19 group compared to the prior-to-COVID-19 group (RR 1.44, 95%CI 1.26-1.65; = 64%). Only two studies reported the risk of DKA among patients with established type 1 diabetes and the cumulative risk was not statistically significant. In the sensitivity analysis, four studies reported an adjusted odds ratio (aOR) of the risk of DKA during COVID-19 compared to the prior-to-COVID-19 period. The fixed estimate from the meta-analysis found an increase in the risk of DKA in the during-COVID-19 group compared to the prior-to-COVID-19 group (aOR 2.04, 95%CI 1.66-2.50).
CONCLUSIONS
This study showed that DKA risk, especially the risk of severe DKA, has increased significantly during the pandemic. Healthcare systems must be aware and prepared for such an increase in DKA cases and take all necessary measures to prevent future spikes during the pandemic.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272775, identifier PROSPERO [CRD42021272775].
Topics: COVID-19; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Incidence; Pandemics; Pediatrics
PubMed: 35355556
DOI: 10.3389/fendo.2022.856958 -
Frontiers in Endocrinology 2023The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain... (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.
OBJECTIVE
The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.
RESULTS
Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.
CONCLUSION
Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Topics: Female; Humans; Male; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Nasopharyngitis; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38027214
DOI: 10.3389/fendo.2023.1256548 -
Cureus Oct 2022The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30... (Review)
Review
The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30 and under. In this meta-analysis, the Overall use of IV insulin in patients with mild/moderate vs. severe diabetic ketoacidosis was compared in randomized controlled trial articles from January 2011 to December 2021 using EMBASE, Medline, and CENTRAL. Only 8 of 3258 studies met the inclusion criteria. This review shows that intravenous insulin can significantly decrease plasma glucose and potassium levels in mild/moderate cases and severe cases. However, it can decrease the resolution time of acidosis more quickly in mild/moderate cases than in severe cases. In the current meta-analysis, the use of IV insulin is secure and efficient. There was no discernible difference in the effectiveness of IV insulin between mild/moderate and severe DKA.
PubMed: 36439560
DOI: 10.7759/cureus.30721 -
Frontiers in Pharmacology 2023As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients...
Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis.
As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis. Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis. Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)]. Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.
PubMed: 38044937
DOI: 10.3389/fphar.2023.1303694 -
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 -
PloS One 2021Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by... (Meta-Analysis)
Meta-Analysis
Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis.
BACKGROUND AND AIMS
Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM).
METHODS
We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region.
RESULTS
Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20-30)% or < 15%, (15-30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3-4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States.
CONCLUSIONS
The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.
Topics: Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glucose; Heart Failure; Humans; Hypoglycemic Agents; Metformin; Myocardial Infarction; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33606705
DOI: 10.1371/journal.pone.0244689 -
The Journal of International Medical... Nov 2023To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection.
AIMS
To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection.
METHODS
PubMed and Scopus library databases were screened for relevant case reports published between January 2020 and June 2022. Study design, geographic region or language were not restricted.
RESULTS
Twenty studies were identified and involved 37 patients (20 [54%] male, 17 [46%] female). Median age was 11.5 years (range 8 months-33 years) and 31 (84%) patients were aged ≤17 years. Most patients (33, 89%) presented with diabetic ketoacidosis (DKA). In total, 23 (62%) patients presented at the time of positive COVID-19 testing and 14 (38%) had symptoms consistent with COVID-19 infection or a previous positive test (1-56 days). Diabetes symptomatology was provided in 22 cases and (19, 86%) reported polyuria, polydipsia, polyphagia, fatigue, or weight loss or a combination of the aforementioned in the preceding weeks (3 days-12 weeks). Of the 28 patients that had data on acute and long-term treatment, all recovered well and most were managed with basal bolus insulin regimens. Quality assessment showed that most reports were either 'good' or 'moderate quality'.
CONCLUSIONS
Although uncommon, new-onset T1D is a condition healthcare professionals may expect to see following a COVID-19 infection.
Topics: Female; Humans; Infant; Male; COVID-19; COVID-19 Testing; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Polyuria; Case Reports as Topic
PubMed: 37940619
DOI: 10.1177/03000605231210403