Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.

PURPOSE: To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D. METHODS: We searched several databases and grey literature sources. Eligible trials had at least 12 weeks of intervention, included patients with T2D, and assessed the efficacy of glucose-lowering drugs as monotherapies. The primary outcome of interest was absolute reduction in liver fat content (LFC), assessed by means of MRI. Secondary efficacy outcomes were reduction in visceral and subcutaneous adipose tissue. We performed random effects frequentist network meta-analyses to estimate mean differences (MDs) with 95% confidence intervals (CIs). We ranked treatments based on P-scores. RESULTS: We included 29 trials with 1906 patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (P-score 0.84) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (0.71) were the most efficacious in terms of liver fat content reduction. Among individual agents, empagliflozin was the most efficacious (0.86) and superior to pioglitazone (MD -5.7, 95% CI -11.2 to -0.3) (very low confidence). GLP-1 RAs had also the most favorable effects on visceral and subcutaneous adipose tissue. CONCLUSIONS: GLP-1 RAs and SGLT-2 inhibitors seem to be the most efficacious glucose-lowering drugs for liver steatosis in patients with T2D. Assessment of their efficacy on NAFLD in patients irrespective of presence of T2D is encouraged.

Effect of Glucagon-like Peptide-1 Receptor Agonists on Cardio-Metabolic Risk Factors among Obese/Overweight Individuals Treated with Antipsychotic Drug Classes: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute a drug class primarily developed for the treatment of subjects with type 2 diabetes, although they have also provided significant benefit for subjects with obesity without underlying diabetes. Individuals with psychotic disorders who are receiving antipsychotic treatment are a patient population at risk of developing obesity, which is linked to other metabolic disturbances. METHODS: We searched PubMed and the Cochrane Library from inception to 1 December 2022, for randomized controlled trials (RCTs) enrolling obese or overweight adult subjects with an underlying psychotic disorder treated with antipsychotic drugs, randomized either to GLP-1RAs or a control. We set as the primary efficacy outcome the change in body weight and as secondary efficacy outcomes the change in body mass index (BMI) and in waist circumference, along with indices of glycemia, lipid profile, and blood pressure. RESULTS: We pooled data from 4 trials (2 with liraglutide and 2 with exenatide) in a total of 199 enrolled subjects. GLP-1RA treatment, compared to control, resulted in a significant decrease in body weight by 3.8 kg [mean difference (MD) = -3.80, 95% CI; -6.35 to -1.24, I2 = 64%]. In addition, GLP-1RA treatment led to a significant decrease in BMI, compared to control, of 1.04 kg/m2 (MD = -1.04, 95% CI; -1.92 to -0.17, I2 = 35%). However, no significant effect on waist circumference was shown (MD = -3.2, 95% CI; -6.47 to 0.08, I2 = 88%). A significant improvement in glycemia and lipid profiles was also demonstrated with GLP-1RAs. No subgroup difference between liraglutide and exenatide was shown, and the use of GLP-1RAs did not increase the risk for treatment discontinuation compared to the control group. CONCLUSION: Treatment with GLP-1RAs can significantly improve weight loss and other cardiometabolic risk factors in obese people taking antipsychotic medications.

How Should Concurrent Arterial and Venous Thrombosis Associated With SARS-CoV-2 Infection Be Managed?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with a high incidence of thrombotic complications involving both the arterial and the venous systems. However, concurrent arterial and venous thrombosis is extremely rare. Herein, we present the case of a 75-year-old male patient with severe COVID-19 who developed bilateral renal artery thrombosis and pulmonary embolism during the disease course. To our knowledge, this is the first such case described in the literature. LEARNING POINTS: SARS-CoV-2-related coagulopathy is associated with both arterial and venous thrombotic events, which increase morbidity and mortality.Concurrent arterial and venous thrombotic events attributed to SARS-CoV-2 are extremely rare.A high index of clinical suspicion is required, while further research is needed to determine the optimal type, dose and duration of anticoagulation in such cases.

Sotagliflozin for patients with type 2 diabetes: A systematic review and meta-analysis.

AIM: To assess the efficacy and safety of sotagliflozin in patients with type 2 diabetes. METHODS: We searched Medline, Embase, the Cochrane Library, and grey literature sources up to August 2021 for randomized controlled trials (RCTs) that compared sotagliflozin with placebo or other antidiabetic agents in patients with type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed three secondary efficacy and 15 safety outcomes. We synthesized data using weighted mean differences (WMDs) and odds ratios (ORs), along with 95% confidence intervals (CIs). RESULTS: We included 11 RCTs comprising 16 411 subjects in the meta-analysis. Compared with placebo, sotagliflozin reduced HbA1c (WMD -0.42%, 95% CI -0.56 to -0.29), body weight (WMD -1.33 kg, 95% CI -1.57 to -1.09), and systolic blood pressure (WMD -2.44 mmHg, 95% CI -2.81 to -2.07). No difference was evident against other active comparators. Sotagliflozin reduced myocardial infarction (OR 0.72, 95% CI 0.54 to 0.97) and heart failure (OR 0.68, 95% CI 0.58 to 0.79) compared with placebo, and had a neutral effect on all-cause mortality, cardiovascular mortality, and stroke. Treatment with sotagliflozin was safe regarding the incidence of serious adverse events, hypoglycaemia, and diabetic ketoacidosis. Nevertheless, it was associated with an increased incidence of diarrhoea, genital infections, and volume depletion events. CONCLUSIONS: Sotagliflozin reduces blood glucose, body weight, and systolic blood pressure, and demonstrates a beneficial effect on heart failure and myocardial infarction. Its overall safety profile is comparable with other sodium-glucose co-transporter-2 inhibitors.

Takayasu Arteritis is Associated with Impaired Arterial Stiffness: A Meta-Analysis of Observational Studies.

Introduction/Objective: Takayasu arteritis, a large vessel vasculitis, is strongly associated with increased risk for cardiovascular and chronic kidney disease. Arterial stiffness represents an established prognostic marker of cardiovascular disease development in the general population. A few studies have assessed the effect of Takayasu arteritis on arterial stiffness indices. Herein, we sought to provide pooled effect estimates regarding the impact of Takayasu arteritis on arterial stiffness, by retrieving relevant, available observational studies. Methods: On 1st May, 2022, we searched two major electronic databases and grey literature sources for relevant observational studies. We set as primary outcome the mean difference in carotid femoral PWV (cfPWV) between patients with Takayasu arteritis compared to controls. Results: Regarding the primary outcome, we pooled data from 3 studies in a total of 125 enrolled subjects, demonstrating that Takayasu arteritis is associated with a significant increase in cfPWV by 2.06 m/s (MD = 2.06, 95% CI; 1.29 - 2.83, I2 = 0%, p < 0.001), compared to controls. Conclusion: The present preliminary meta-analysis demonstrates the potential deleterious effects of Takayasu arteritis on arterial stiffness. Prognostic implications must be confirmed in larger, prospective studies.

Ultra-rapid-acting insulins for adults with diabetes: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis of randomized controlled trials to assess the efficacy and safety of the novel, ultra-rapid-acting insulins aspart and lispro in adults with type 1 or type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed eight efficacy and six safety endpoints. We calculated weighted mean differences (WMD) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, alongside 95% confidence intervals (CIs). We additionally assessed statistical heterogeneity among studies with the I2 statistic, considering values greater than 60% as indicative of substantial heterogeneity. Nine studies comprising 5931 patients were included in the systematic review; eight active-controlled studies could be synthesized in terms of a meta-analysis. Treatment with ultra-rapid-acting insulins had a similar effect on change in HbA1c compared with rapid-acting insulins (WMD -0.02%, 95% CI -0.08 to 0.05, I2  = 61% for patients with type 1 diabetes and -0.02%, 95% CI -0.09 to 0.04, I2  = 19% for patients with type 2 diabetes). Similarly, no difference was evident in terms of change in fasting plasma glucose, self-measured plasma glucose, body weight, basal or bolus insulin dose, incidence of serious adverse events and hypoglycaemia. Compared with rapid-acting insulins, ultra-rapid-acting insulins reduced 1- and 2-hour postprandial glucose (PPG) increment based on a liquid meal test, both in patients with type 1 and type 2 diabetes (WMD -0.94 mmol/L, 95% CI -1.17 to -0.72, I2  = 0% and -0.56 mmol/L, 95% CI -0.79 to -0.32, I2  = 0%, respectively, for change in 1-hour PPG increment). In conclusion, ultra-rapid-acting insulins were as efficacious and safe as rapid-acting insulins, showing a favourable effect solely on PPG control.

Comparative efficacy and safety of glucose-lowering drugs as adjunctive therapy for adults with type 1 diabetes: A systematic review and network 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.

Delayed Diagnosis and Treatment of a Critically Ill Patient with Infective Endocarditis Due to a False-Positive Molecular Diagnostic Test for SARS-CoV-2.

BACKGROUND The worldwide spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) has created unprecedented situations for healthcare professionals and healthcare systems. Although infection with this virus is considered the main health problem currently, other diseases are still prevalent. CASE REPORT This report describes a 59-year-old man who presented with symptoms of dyspnea and fever that were attributed to Covid-19 infection. His clinical condition deteriorated and further examinations revealed a subjacent severe aortic regurgitation due to acute infective endocarditis. Surgical treatment was successful. CONCLUSIONS The results of diagnostic tests for Covid-19 should be re-evaluated whenever there are clinical mismatches or doubts, as false-positive Covid-19 test results can occur. Clinical interpretation should not be determined exclusively by the Covid-19 pandemic. This case report highlights the importance of using validated and approved serological and molecular testing to detect infection with SARS-CoV-2, and to repeat tests when there is doubt about presenting symptoms.

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis.

AIM: To assess the efficacy and safety of oral semaglutide, a novel glucagon-like peptide-1 receptor agonist, for patients with type 2 diabetes. METHODS: We searched Medline, Embase, the Cochrane Library and grey literature sources up to July 1, 2019 for randomized controlled trials (RCTs) comparing oral semaglutide with placebo or other antidiabetic agents. The primary outcome was change from baseline in HbA1c. Secondary outcomes included change from baseline in body weight and blood pressure, cardiovascular endpoints, severe hypoglycaemia, gastrointestinal adverse events and diabetic retinopathy. We synthesized results using weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, along with 95% confidence intervals (CIs). RESULTS: We included 11 RCTs with 9890 patients in the systematic review. Compared with placebo, oral semaglutide reduced HbA1c and body weight (WMD -0.89%, 95% CI -1.07 to -0.71 and - 2.99 kg, 95% CI -3.69 to -2.30, respectively). Oral semaglutide was also superior to other active comparators (including liraglutide, empagliflozin and sitaglipitin) in terms of lowering HbA1c (WMD -0.35%, 95% CI -0.43 to -0.26) and reduction of body weight (WMD -1.48 kg, 95% CI -2.28 to -0.67), and had a favourable effect on systolic blood pressure. Compared with placebo, oral semaglutide reduced all-cause mortality (OR 0.58, 95% CI 0.37 to 0.92) and cardiovascular mortality (OR 0.55, 95% CI 0.31 to 0.98), and had a neutral effect on myocardial infarction, stroke, severe hypoglycaemia and diabetic retinopathy. However, treatment with oral semaglutide increased the incidence of nausea, vomiting and diarrhea, while events of acute pancreatitis were rare. CONCLUSIONS: Oral semaglutide can effectively and safely reduce blood glucose, body weight and systolic blood pressure. Nevertheless, it is associated with increased incidence of gastrointestinal adverse events. Further research is needed to clarify its long-term safety and comparative effectiveness against other antidiabetic agents.

Causes of secondary hypertension from a single center in Northern Greece; a retrospective clinical study.

Hypertension constitutes one of the most common diseases leading patients to the Outpatient Departments. Idiopathic hypertension is the prevailing type, but on the other hand, the possible presence of clinical entities responsible for the development of secondary hypertension should never be underestimated. We retrospectively studied 447 subjects aged between 20 and 84 years old and diagnosed with hypertension, who were thoroughly evaluated for secondary hypertension. Our analysis demonstrated that 35 out of the 447 subjects were finally diagnosed with secondary hypertension, representing a relative frequency of 7.8%. Most common causes of secondary hypertension identified in our study group were: glucocorticoid intake (n = 14), obesity hypoventilation syndrome (n = 6), obstructive sleep apnea (n = 2) and preeclamspia (n = 2). Several other causes are also reported. Our study, conducted in a single center in Northern Greece, confirms previous reports concerning the prevalence of secondary hypertension among Greek patients, shedding light on potential pathophysiologic mechanisms. In conclusion, a high proportion of hypertensive individuals still feature have an underlying cause, thus, diagnostic work-up should be thorough and exhaustive, in order the correct diagnosis to be made and the targeted treatment to be initiated.