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Current Problems in Cardiology May 2024Despite effectiveness of sodium-glucose cotransporter 2 (SGLT 2) inhibitors, concerns have been raised about the potential side effects of these drugs. Thus, a... (Review)
Review
PURPOSE
Despite effectiveness of sodium-glucose cotransporter 2 (SGLT 2) inhibitors, concerns have been raised about the potential side effects of these drugs. Thus, a pharmaco-vigilance study was designed that aims to identify any discrepancies between the reported adverse events & assess the safety profile of SGLT2 inhibitors.
METHODS
We studied diabetic ketoacidosis (DKA), euglycemic DKA, amputation, urinary tract infection (UTI), mycotic genital infection & hypotension associated with empagliflozin, dapagliflozin, canagliflozin & ertugliflozin in RCTs and reporting databases. WHO's VigiBase, FAERS, EMA's EudraVigilance & DAEN were thoroughly studied to obtain spontaneously reported real-world adverse events.
RESULTS
Different SGLT2 inhibitors exhibit varied side effect profiles. Additionally, the findings suggest that adverse events may be more likely to occur in a broader population in the real world than in a highly inclusive clinical trial subset CONCLUSION: Our study provides comparison of the real world reported adverse events to adverse events reported in the clinical trials studying the efficacy of SGLT 2 inhibitors.
PubMed: 38789017
DOI: 10.1016/j.cpcardiol.2024.102664 -
Metabolites May 2024An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations.... (Review)
Review
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.
PubMed: 38786741
DOI: 10.3390/metabo14050264 -
Diabetes, Obesity & Metabolism May 2024Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among...
AIM
Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents.
MATERIALS AND METHODS
Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates.
RESULTS
The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference.
CONCLUSIONS
SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.
PubMed: 38779879
DOI: 10.1111/dom.15682 -
Journal of Translational Internal... Apr 2024
PubMed: 38779117
DOI: 10.2478/jtim-2023-0144 -
Diabetes Care May 2024To examine the effects of insulin-adjunctive therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon receptor antagonist (GRA) on glycemia,...
OBJECTIVE
To examine the effects of insulin-adjunctive therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon receptor antagonist (GRA) on glycemia, insulin use, and ketogenesis during insulinopenia in type 1 diabetes.
RESEARCH DESIGN AND METHODS
In a randomized, double-blind, placebo-controlled, crossover trial we assessed the effects of adjunctive SGLT2 inhibitor therapy (dapagliflozin 10 mg daily) alone and in combination with the GRA volagidemab (70 mg weekly) in 12 adults with type 1 diabetes. Continuous glucose monitoring, insulin dosing, and insulin withdrawal tests (IWT) for measurement of glucose and ketogenesis during insulinopenia were completed during insulin-only (Baseline), SGLT2 inhibitor, and combination (SGLT2 inhibitor + GRA) therapy periods.
RESULTS
Average glucose and percent time with glucose in range (70-180 mg/dL) improved with combination therapy versus Baseline and SGLT2 inhibitor (131 vs. 150 and 138 mg/dL [P < 0.001 and P = 0.01] and 86% vs. 70% and 78% [P < 0.001 and P = 0.03], respectively) without increased hypoglycemia. Total daily insulin use decreased with combination therapy versus Baseline and SGLT2 inhibitor (0.41 vs. 0.56 and 0.52 units/kg/day [P < 0.001 and P = 0.002]). Peak β-hydroxybutyrate levels during IWT were lower with combination therapy than with SGLT2 inhibitor (2.0 vs. 2.4 mmol/L; P = 0.048) and similar to levels reached during the Baseline testing period (2.1 mmol/L). Participants reported enhanced treatment acceptability and satisfaction with combination therapy.
CONCLUSIONS
Glucagon antagonism enhances the therapeutic effects of SGLT2 inhibition in type 1 diabetes. Combination therapy improves glycemic control, reduces insulin dosing, and suggests a strategy to unlock the benefits of SGLT2 inhibitors while mitigating the risk of diabetic ketoacidosis.
PubMed: 38776437
DOI: 10.2337/dc24-0212 -
Cureus Apr 2024Sodium-glucose transport protein 2 inhibitors (SGLT2i) are becoming commonplace in many chronic diseases: type 2 diabetes mellitus, heart failure, and chronic kidney...
Sodium-glucose transport protein 2 inhibitors (SGLT2i) are becoming commonplace in many chronic diseases: type 2 diabetes mellitus, heart failure, and chronic kidney disease. We present the case of a 65-year-old male with a history of type 2 diabetes who had been on an SGLT2i for over 12 months and was found to have euglycemic diabetic ketoacidosis (eDKA) occurring concurrently with a thyroid storm. This case report illustrates a unique scenario of two endocrine emergencies occurring simultaneously.
PubMed: 38774158
DOI: 10.7759/cureus.58696 -
Diabetology & Metabolic Syndrome May 2024Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity....
BACKGROUND
Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer.
METHODS
We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity.
RESULTS
Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I = 0%).
CONCLUSIONS
SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.
PubMed: 38773486
DOI: 10.1186/s13098-024-01354-4 -
Diabetes Research and Clinical Practice Jun 2024We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). (Observational Study)
Observational Study
AIMS
We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS).
METHODS
A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors.
RESULTS
A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia.
CONCLUSIONS
The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies.
TRIAL REGISTRATION
This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016).
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Diabetic Ketoacidosis; Hyperglycemic Hyperosmolar Nonketotic Coma; Aged; Adult; Bacteremia; C-Reactive Protein; Japan; Risk Factors; Procalcitonin; Biomarkers
PubMed: 38772502
DOI: 10.1016/j.diabres.2024.111713 -
Clinical Case Reports May 2024In the context of diabetic ketoacidosis, clinicians should consider uncommon origins of infection, notably infective endocarditis. This is especially crucial when...
In the context of diabetic ketoacidosis, clinicians should consider uncommon origins of infection, notably infective endocarditis. This is especially crucial when confronted with cases that recur persistently or exhibit resistance to treatment. This is a case of a diabetic patient with diabetic ketoacidosis admitted to our facility. A 35-year-old diabetic patient presented with DKA precipitated by mitral valve endocarditis. To our knowledge and according to the literature review, only one case of DKA precipitated by endocarditis has been reported in the past. This report highlights the importance of considering endocarditis as a possible etiology in patients presenting.
PubMed: 38770414
DOI: 10.1002/ccr3.8824 -
Journal of Oncology Pharmacy Practice :... May 2024Immunotherapy has a crucial role in the current treatment of multiple malignancies. Albeit described as rare, new onset autoimmune diabetes is a potentially...
INTRODUCTION
Immunotherapy has a crucial role in the current treatment of multiple malignancies. Albeit described as rare, new onset autoimmune diabetes is a potentially life-threatening complication of programmed cell death-1 (PD-1) inhibitors, such as pembrolizumab, and its predisposing factors and pathological mechanism are yet to be clarified.
CASE REPORT
We present a case of a 72-year-old man with a high-grade bladder carcinoma undergoing pembrolizumab treatment. He had no personal or family history of diabetes mellitus but was diagnosed with primary hypothyroidism four months after starting pembrolizumab. Two years after starting pembrolizumab, he presented in the emergency department due to abdominal pain, anorexia, polydipsia, polyuria and vomiting over the preceding five days and he met criteria for severe diabetic ketoacidosis (DKA). Three days prior to his admission, he had received prednisolone therapy for suspected hypersensitivity related to a contrast-enhanced imaging that he performed.
MANAGEMENT & OUTCOME
Prompt treatment for DKA was started, with transition to insulin basal-bolus therapy after DKA resolution, with progressive glycaemic stabilization. Further investigation revealed low C-peptide levels (0.07 ng/dL, with a fasting blood glucose of 288 mg/dL), HbA1c 9.2% and positive anti-IA2 antibodies, which allowed the diagnosis of new-onset autoimmune diabetes. Pembrolizumab was transiently suspended, and the patient resumed treatment after glycaemic profile optimization under multiple daily insulin administrations two months later.
DISCUSSION
This case highlights the importance of clinical suspicion and glycaemic monitoring as an integral part of treatment protocols in patients on pembrolizumab and other immune checkpoint inhibitors. Additional research and investigation into the underlying mechanisms of this condition are necessary to identify potential screening tests for individuals at higher risk of developing DM and to guide the implementation of management and preventive strategies for ketoacidosis complication.
PubMed: 38766907
DOI: 10.1177/10781552241255699