Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience.

BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse. AIM: To study the comparative efficacy and safety of SGLT-2i using real-world clinical data. METHODS: We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively. RESULTS: Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin - 78.0 (25.3), canagliflozin - 80.0 (25.5), and empagliflozin - 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin - 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection - 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin. CONCLUSION: Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

Surveillance on Adverse Events Following COVISHIELD (ChAdOx1 nCoV-19) vaccination in Goa, India: An Observational Study.

BACKGROUND: COVISHIELD, ChAdOx1 nCoV- 19 Corona Virus Vaccine was granted emergency use authorization (EUA) as the first vaccine in India in January 2021. Knowing what to anticipate after vaccination will reduce vaccine hesitancy in the public. This study aimed to identify and measure the adverse events following COVID-19 vaccination. MATERIALS AND METHODS: A cross-sectional observational study was conducted at Goa Medical College, starting on February 21 till May 23, 2021. A total of 418 people were enrolled. We collected the data using the Microsoft Form and analyzed using Microsoft Excel and R-program. RESULTS: Of the 418 vaccine recipients, the incidence rate of AEFI (Adverse Events Following Immunization) was 54.31%. Fever, fatigue, and headache were the most commonly reported systemic AEFIs. Among these, 54.7% of AEFI were mild, 42.38% were of the moderate category, and only 2.96% were of grade 3 severity. None of the AEFIs were severe enough for hospitalization. Most of them developed symptoms within 24 hours of the first dose. Complete recovery from AEFIs took a median time of 24 hours. CONCLUSION: Most of our study findings were consistent with the phase 1, 2/3 trials findings of Oxford-AstraZeneca's ChAdOx1 vaccine. The AEFI symptoms were considered immune reactions to the vaccine. The AEFIs were more common among younger individuals and females. The chance of missing a serious adverse event like a thromboembolic phenomenon cannot be ruled out. We observed low AEFI rates with COVISHIELD in the Indian population compared to Oxford- AstraZeneca's ChAdOx1 vaccine in the UK-based population, which can be explained by preexisting immunity against adenovirus in the Indian population. However, based on the study findings, we may interpret that the COVISHIELD, Serum Institute of India, carries a good safety profile overall.

Clinical Profile and Factors Associated with Adverse Outcomes in Coronavirus Disease 2019-associated Mucormycosis: A Single-centre Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic was associated with an increased incidence of mucormycosis globally. However, the clinical pattern, epidemiologic features and risk factors for adverse outcomes are not well established. Methods: We performed a retrospective analysis of the data from patients hospitalized with proven mucormycosis between April 2021 and August 2021. Patients were managed with a multi-disciplinary approach involving medical, surgical, and comorbidity treatment. The clinical presentation, management details, complications and outcomes, including mortality, were reviewed from clinical records. Results: The mean age of presentation was 53.7 (± 11.8) years, and 88 (84.6%) were men. Of the 104 cases with COVID-19-associated mucormycosis, 97 (93.27%) patients had diabetes, and 80.8% had a haemoglobin A1C (HbA1c) of ≥6.4% at diagnosis. Seventy percent of diabetes cases experienced steroid-induced hyperglycaemia during treatment. Even with appropriate treatment, 17 (16.35%) patients died. High HbA1c and creatinine levels, presence of chronic kidney disease (CKD), need for intensive care unit admission, and orbital evisceration were the risk factors associated with high mortality on multivariate logistic regression analysis. Cox regression analysis revealed that the overall mortality increased by a factor of 12% with each 1 percentage point increase in HbA1c ≥6.4% (hazard ratio 1.12; 95% confidence interval 0.95- 1.31). The mortality risk was even higher when diabetes was associated with CKD (hazard ratio 1.82; 95% confidence interval 0.24-14.00). Conclusion: High HbA1c and creatinine levels, intensive care unit admission, CKD, and aggressive disease requiring orbital evisceration are the predictors of mortality in patients with COVID-19-associated mucormycosis. Patients with these risk factors should be managed more actively to reduce morbidity and mortality.

Pioglitazone improves hepatic mitochondrial function in a mouse model of nonalcoholic steatohepatitis.

Pioglitazone is effective in improving insulin resistance and liver histology in patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism is a central feature of NASH, we hypothesized that an important target of pioglitazone would be alleviating mitochondrial oxidative dysfunction. To this end, we studied hepatic mitochondrial metabolism in mice fed high-fructose high-transfat diet (TFD) supplemented with pioglitazone for 20 wk, using nuclear magnetic resonance-based 13C isotopomer analysis. Pioglitazone improved whole body and adipose insulin sensitivity in TFD-fed mice. Furthermore, pioglitazone reduced intrahepatic triglyceride content and fed plasma ketones and hepatic TCA cycle flux, anaplerosis, and pyruvate cycling in mice with NASH. This was associated with a marked reduction in most intrahepatic diacylglycerol classes and, to a lesser extent, some ceramide species (C22:1, C23:0). Considering the cross-talk between mitochondrial function and branched-chain amino acid (BCAA) metabolism, pioglitazone's impact on plasma BCAA profile was determined in a cohort of human subjects. Pioglitazone improved the plasma BCAA concentration profile in patients with NASH. This appeared to be related to an improvement in BCAA degradation in multiple tissues. These results provide evidence that pioglitazone-induced changes in NASH are related to improvements in hepatic mitochondrial oxidative dysfunction and changes in whole body BCAA metabolism.