The Renal Composite Benefit of Sodium Glucose Co-Transporter 2 Inhibitors Should Ideally Be Assessed Based on a Standardised Definition: A Meta-Analysis of Randomised Controlled Trials.

(1) Background: Chronic kidney disease (CKD) is extremely common against the backdrop of type 2 diabetes (T2D), accounting for nearly 30-40% of cases. The conventional management strategy relie predominantly on metabolic control and the renin-angiotensin-aldosterone system (RAAS) blockage. In the last decade, sodium glucose cotransporter 2 inhibitors (SGLT-2is) have emerged as the leading molecules preventing the development of, as well as retarding, the progression to CKD. Although the evidence in support of SGLT-2is is overwhelming, the definition of renal composite outcome in the trials varied considerably. The aim of the present meta-analysis was to explore the robustness of the renal composite benefits using a uniform definition. (2) Methods: A web-based search was conducted using the Cochrane Library to identify the relevant articles for meta-analysis. RStudio (1 July 2022, Build 554) software was used to conduct the meta-analysis. Hazard ratio (HR) was the effect size used to estimate the renal composite benefit, and prediction interval was used to detect heterogeneity. In view of the differing baseline characteristic of the trials as well as different molecules used, a random effects model was used. (3) Results: There were 12 trials including 78,781 patients, identified using the search strategy, and a five-point Cochrane risk-of-bias was used to assess quality of the publications. In the overall estimation (irrespective of the definition used for the renal composite) the HR was 0.68 (95% CI 0.60-0.76, prediction interval: 0.48-0.95) in favour of SGLT-2is, devoid of heterogeneity. While using a uniform definition of eGFR ≥ 40%decline, ESKD, or renal death, the HR was 0.64 (95% CI 0.53-0.78); using eGFR ≥ 50%decline, ESKD, or renal death the HR was 0.75 (95% CI 0.59-0.97); and with doubling of serum creatinine, renal replacement therapy, or renal death, the HR was 0.67 (95% CI 0.55-0.83) in favour of SGLT-2is. However, significant heterogeneity was encountered with all these three definitions. (4) Conclusion: There is a need to analyse the renal outcomes using a uniform definition in future trials. The presence of heterogeneity might disappear with the pooling of larger number of trials. However, if heterogeneity persists, we need to identify other clinical or laboratory attributes (in addition to SGLT-2is) responsible for the positive renal outcomes.

Exploring the comparative cardiovascular death benefits of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a frequentist and Bayesian network meta-analysis-based scoring.

Background and aims: Cardiovascular death (CV death) is the most objective component of the primary or secondary endpoint in cardiovascular outcome trials (CVOTs) conducted with sodium-glucose cotransporter 2 inhibitors (SGLT-2is). CV death is often incorporated into primary composite outcomes. It is combined with major adverse cardiovascular events (MACEs) in trials with atherosclerotic cardiovascular disease (ASCVD) at baseline and with hospitalization due to heart failure (hHF) in trials with heart failure at baseline. Unlike the primary composites, CV death reduction by itself demonstrated significant variations among the CVOTs with SGLT-2is. Moreover, the impact of the individual agents within the SGLT-2i group on the reduction in CV death has not been explored objectively. This network meta-analysis was undertaken to construct a hierarchy based on indirect pairwise comparisons and rankings among the individual agents within SGLT-2is. Methods: A Cochrane library-based web search yielded 13 randomized controlled trials for analysis. Stata/BE 17.0 and RStudio 2022.07.1 Build 554 software were used to conduct a frequentist and Bayesian network meta-analysis. The effect size was assessed based on the risk ratio (RR). Ranking of the individual agents was performed with a frequentist approach (P-score and a multidimensional scaling [MDS] rank system) and a Bayesian ranking (surface under the cumulative ranking [SUCRA]). Results: Regarding the overall data, SGLT-2is reduced the CV death risk by 12% (RR: 0.88, 95% CI 0.80-0.96). All three scoring methods resulted in empagliflozin scoring the highest. There was a 15% RR reduction in CV death (95% CI 0.71-1.02) in the ASCVD and multiple cardiovascular risk factor (MRF) groups and an 11% RR reduction in the HF group, with empagliflozin ranking the highest in the former group and dapagliflozin in the latter. Conclusions: Empagliflozin ranked the highest compared to the other SGLT-2is in the overall population and the trials including type 2 diabetes (T2D) patients with ASCVD or MRF at baseline, while dapagliflozin ranked the highest in the trials of patients with HF at baseline. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022381556, identifier CRD42022381556.

Finerenone in type 2 diabetes and renal outcomes: A random-effects model meta-analysis.

Background: The nonsteroidal mineralocorticoid antagonist finerenone is a new addition to the list of agents (angiotensin converting enzyme inhibitors and sodium glucose cotransporter 2 inhibitors) conferring renal protection to patients with diabetic kidney disease. Two recent meta-analyses using the fixed effect model in patients with chronic kidney disease (both diabetic and nondiabetic populations) came to a conflicting conclusion on the effect of finerenone on eGFR decline. This meta-analysis was undertaken exclusively in the type 2 diabetes (T2D) population to explore the robustness and heterogeneity of the effect size by conducting a random effects model meta-analysis along with draft plots and prediction intervals. Materials and methods: A database search was conducted using the Cochrane library, PubMed, and Embase to identify relevant citations. Analysis was conducted on the 14th of September 2022, using RevMan 5.4.1 and RStudio (2022.07.1, Build 554). The hazard ratio was used as the effect size for the renal composite, while the standardized mean difference (SMD) was used to estimate the effect size of eGFR decline and reduction in the urine albumin creatinine ratio (UACR). The Cochrane risk-of-bias was used to assess the quality of the studies. The primary outcome assessed was the renal composite defined as kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. Results: A pooled population of 13,943 patients from four citations was included for analysis. The Cochrane risk of bias was used to assess the quality of the studies. There was a significant 16% reduction in the renal composite (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes) [HR: 0.84, 95% CI 0.77-0.92, 2: 0, I2: 0%). Finerenone was also associated with reduction in UACR (SMD: -0.49, 95% CI -0.53 to -0.46, τ2: < 0.0001, I2: 0%, prediction interval: -0.57 to -0.41) and prevention of decline in eGFR (SMD: -0.32, 95% CI -0.37 to -0.27, τ2: < 0.0001, I2: 0%, prediction interval: -0.43 to -0.21) without any evidence for significant heterogeneity. Except for an increase in hyperkalaemia (RR: 2.22, 95% CI 1.93-2.24), adverse events were observed with fineronone compared to placebo (RR: 1.00, 95% CI 0.98-1.01). Conclusion: There are significant benefits in renal outcomes associated with finerenone treatment in T2D patients with established chronic kidney disease with a side effect profile comparable to placebo.

Heterogeneity in cardiovascular death or hospitalization for heart failure benefits with flozins is linked to weight.

AIMS: Cardiovascular outcome trials with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have documented a positive impact on micro- and macrovascular complications of type 2 diabetes (T2D). Most analyses suggest that these benefits are independent of achieving metabolic control. This meta-regression analysis was undertaken to explore the relationship between metabolic components positively influenced by SGLT-2is and a reduction in cardiovascular death (CV death) or hospitalization due to heart failure (hHF). METHODS AND RESULTS: A database search was conducted using the Cochrane Library to identify relevant studies. Analysis was conducted using CMA and RStudio (2022.07.1) software. The hazard ratios of the individual studies were used to compute the random effects model mean effect size for CV death or hHF, and the prediction interval was used to identify the uncertainty in the summary treatment effect. Heterogeneity was quantified using Q statistics. A pooled population of 46 969 patients from five studies was included for analysis. The Cochrane risk of bias tool was used to assess the quality of the studies. There was a significant 23% reduction in CV deaths or hHFs in the SGLT-2i arm compared with the placebo arm [hazard ratio (HR): 0.77, 95% confidence interval (CI) 0.70-0.85]. However, the prediction interval (0.57-1.05) and the Q statistics [8.06 > degrees of freedom (df) of 4] were indicative of uncertainty in the true effect or heterogeneity. Nearly 50% of the variance of the observed effects were related to the true effects (I2  = 50%). Among the moderators selected, a significant correlation of the outcomes was found with the weight variable (P < 0.01). Weight differential could explain the entire variance in true effect size (R2  = 1.00) ruling out any sampling error. CONCLUSIONS: The results of this meta-regression analysis suggest that the beneficial effects of SGLT-2is in reducing CV deaths and hHFs are related to the weight variable.

Assessing the Effects of Modern Renoprotective Agents in Preventing Progression of Renal Composite Outcomes in Patients with Type 2 Diabetes: A Network Meta-analysis.

BACKGROUND AND AIMS: Type 2 diabetes is one of the leading causes of the development and progression of diabetic kidney disease, culminating in end-stage renal disease. Approximately two decades after successful implementation of the renin-angiotensin-aldosterone blocking system, three classes of agents [sodium glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists] have shown significant potential to confer renoprotection. This network meta-analysis was undertaken to construct a hierarchy based on indirect pairwise comparisons and rankings among and within these three classes of molecules. METHODS: A Cochrane library-based web search yielded 16 randomized controlled trials for analysis. Stata/BE 17.0 and RStudio 2022.07.1 Build 554 software were used to conduct a frequentist network meta-analysis. The effect size was assessed based on the odds ratio, and the MDS (multidimensional scaling) rank system was used to identify a hierarchy among reno-protective molecules. RESULTS: Regarding the overall data, the SGLT-2i group of agents ranked higher than the other groups in preventing the progression of renal composite events in patients with T2D. Dapagliflozin ranked the highest among individual molecules. CONCLUSIONS: The SGLT-2i group of agents, especially dapagliflozin, is best suited to complement metabolic control in preventing the progression of renal composite outcomes.

The role of oral semaglutide in managing type 2 diabetes in Indian clinical settings: Addressing the unmet needs.

AIMS: Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population. METHODS: We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation. RESULTS: Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population. CONCLUSIONS: Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents.

The cardiovascular benefits of GLP1-RAs are related to their positive effect on glycemic control: A meta-regression analysis.

BACKGROUNDS AND AIMS: Glucagon-like-peptides 1 receptor analogues (GLP1-RAs) have gained primacy in the management of type 2 diabetes (T2D).However, in contrast to the CVOT conducted with sodium glucose cotransporter-2 inhibitors (SGLT-2i)there was a significant reduction in glycated haemoglobin (HbA1c) in some of the CVOT with GLP1-RA. The aim of this analysis is to explore the possible association between cardiovascular outcome benefits with GLP1-RA and HbA1c reduction. METHODS: A Cochrane library based web search yielded 9 eligible citations for this analysis. The analysis was performed using the comprehensive meta-analysis (CMA) software.A meta-regression analysis was performed using HbA1c, weight, and systolic blood pressure reduction as moderators. RESULT: The meta-regression analysis was conducted on a pooled population of 64,236 patients. There was a significant heterogeneity associated with the MACE benefits (Q = 16.88, I2: 52.59, df = 7, p = 0.03). Among the moderators selected to explain the variance in true effects, HbA1c reduction was significant (Q = 7.00, P=<0.001, R2:1.0). Additional meta-regression analysis using 0.9% reduction of HbA1c from baseline indicated an association with MACE benefit (95% CI -0.23 to -0.02, P = 0.01, R2: 0.98). CONCLUSION: The MACE benefits associated with GLP1-RAs are dependent on the reduction of HbA1c levels.

A Meta-Analysis of the Effect of Sodium Glucose Cotransporter-2 Inhibitors on Metabolic Parameters in Patients With Polycystic Ovary Syndrome.

Objective: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome. Methods: We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model. Results: We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, <0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P<0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P=0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P<0.01). Conclusion: SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268564], PROSPERO 2021 CRD42021268564.

A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D).

Treatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction. Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. In a pooled population of 615 patients-297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), - 0.56, 95% CI - 0.88 to - 0.25, P < 0.01], aspartate aminotransferase (SDM, - 0.44, SE, 95% CI - 0.64 to - 0.24, P < 0.01), gamma glutaryl transaminase (SDM, - 0.60, 95% CI - 0.86 to - 0.34, P < 0.01) and reduction in liver fat content (LFC) (SDM, - 0.43, 95% CI - 0.74 to - 0.12, P < 0.01), as well as glycosylated haemoglobin (SDM, - 0.40, 95% CI, - 0.61 to - 0.19, P < 0.01) and weight (SDM, - 0.66, 95% CI, - 0.88 to - 0.44, P < 0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.60, 95% CI 2.67 to 16.29, P < 0.01). This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducing body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824).

A Target HbA1c Between 7 and 7.7% Reduces Microvascular and Macrovascular Events in T2D Regardless of Duration of Diabetes: a Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The target glycated haemoglobin (HbA1c) at which micro- and macrovascular benefits may be derived in type 2 diabetes (T2D) has never been clearly outlined. This meta-analysis was conducted on 15 randomized controlled trials to highlight the association of HbA1c range with outcomes. METHODS: The association of different HbA1c cluster (intention-to-treat (ITT) and end-of-study [EOS]) ranges (≤ 6.5%, 6.6-7.0%, 7.1-7.7%) with micro- and macrovascular complications and also the combined effect of T2D duration (< 10 years or ≥ 10 years) and HbA1c levels was assessed. RESULTS: An intensive glucose-lowering strategy resulted in a significant 17% (95% CI: 0.73-0.93, P < 0.01) reduction in retinopathy, 18% reduction in macroalbuminuria (95% CI 0.62-0.83, P < 0.01), 32% reduction in end-stage renal disease (ESRD) (95% CI 0.36-0.92, P = 0.02) and 13% reduction in non-fatal myocardial infarction (NFMI) (95% CI 0.78-0.96, P < 0.01). Based on HbA1c achieved at EOS, a significant 46% reduction in retinopathy, 52% reduction in macroalbuminuria, 36% reduction in (NFS) non-fatal stroke and a 22% reduction in all-cause mortality (ACM) were observed in the group with HbA1c in the 7.1-7.7% range. In the cohort, with diabetes duration ≥ 10 years, reduction of HbA1c to ≤ 7.0% and significant improvements in new-onset retinopathy (24%) and macroalbuminuria (30%) were offset by an increase in ACM (21%) and NFMI (17%). CONCLUSION: Contrasting with most recommendations, this meta-analysis including recent studies suggests that the optimal HbA1c range for T2D is 7.1-7.7% regardless of diabetes duration.

Meta-analysis of the effects of sodium glucose cotransporter 2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes.

BACKGROUND AND AIM: Sodium glucose cotransporter 2 inhibitors (SGLT-2i), by way of their unique mode of action, present an attractive strategy for the treatment of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), which often coexist and may lead to severe complications. However, the evidence for treatment with SGLT-2i is limited to small heterogeneous studies. Therefore, this meta-analysis was conducted to deduce the effects of SGLT-2i in NAFLD with type 2 diabetes (T2D). METHODS: A web-based search identified nine randomized controlled trials from the Cochrane Library, Embase, and PubMed for this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. RESULT: The outcomes of interest were analyzed from a pooled population of 11 369 patients-7281 on SGLT-2i and 4088 in the control arm. SGLT-2i therapy produced a statistically significant improvement in alanine aminotransferase [standardised mean difference (SDM), -0.21, 95% confidence interval (CI), -0.32 to -0.10, P < 0.01], aspartate aminotransferase (Standardised mean difference (SDM), -0.15, 95% CI, -0.24 to -0.07, P < 0.01), and liver fat as measured by proton density fat fraction (SDM, -0.98, 95% CI, -1.53 to -0.44, P < 0.01) in comparison to standard of care or placebo. In addition, there was a significant reduction in glycosylated hemoglobin (SDM, -0.37, 95% CI, -0.60 to -0.14, P < 0.01) and weight (SDM, -0.58, 95% CI, -0.93 to -0.23, P < 0.01) in the SGLT-2i arm. CONCLUSION: This meta-analysis provides a convincing signal that SGLT-2i have a salutary effect on NAFLD in type 2 diabetes (T2D), probably driven by an improvement of glycemia and body weight, which in turn attenuates hepatic inflammation and hepatic fat accumulation.

Assessing the need for pioglitazone in the treatment of patients with type 2 diabetes: a meta-analysis of its risks and benefits from prospective trials.

The safety and usefulness of pioglitazone (Pio) is repeatedly called into question due to the contradictory information available about it. A meta-analysis and risk benefit assessment was conducted to address the various points of debate regarding Pio. Electronic database search (Cochrane library, Embase & PubMed) resulted in 10 citations eligible for this meta-analysis (prospective, randomised studies), which was conducted using CMA software version 3 (Biostat Inc., Englewood, NJ, USA). The meta-analysis was registered with PROSPERO (ID: CRD42019122403) and compared pioglitazone with a control (anti-hyperglycemic agents without pioglitazone) in patients with either established cardiovascular disease or having high cardiovascular risk. Sensitivity and subgroup analysis were conducted to differentiate the effect of Pio against active controls and placebo. The use of Pio compared to the control group that did not use Pio resulted in a 14% and 23% significant reduction in odds of major adverse cardiac events (MACE: MH-OR, 0.86; 95% CI 0.75-0.98), and stroke (MH-OR, 0.77; 95% CI 0.60-0.99), respectively. This reduction in stroke was not significant in comparison to placebo on subgroup analysis. However, Pio significantly increased odds of heart failure (HF) (MH-OR, 1.47; 95% CI 1.26-1.71) as well as hospitalization for heart failure (hHF) (MH-OR, 1.48; 95% CI 1.21-1.81). In addition, the use of Pio was associated with a significant increase in odds of fractures in women (MH-OR, 2.05; 95% CI 1.28-3.27) and anaemia (MH-OR, 2.56; 95% CI 1.55-4.21). Pio has no significant effect on bladder cancer nor macular oedema. Pio has salutary effects on MACE. The positive effects are completely offset by the harm they seem to cause by way of heart failure, fractures, and anaemia. Pio should therefore be reserved for treatment of T2D with high CV risk or established cardiovascular (CV) disease only in selected patients where other antidiabetics are precluded and not routinely.

"Compliance of the Indian National Task Force guidelines for COVID-19 recommendation by Indian doctors - A survey".

BACKGROUND AND AIMS: As the Coronavirus disease 2019 (COVID-19) pandemic unravels rapidly, there is a glut of confusing and divergent scientific information emanating from differing sources, including the Indian National Task Force for COVID-19. Thus, a web-based survey was conducted to decipher the approach of Indian doctors to the various options for treatment of COVID-19. METHODS: A web-based questionnaire among one lakh doctors across India through email and social media was circulated. After data quality and internal validation, 826 responses were included for analysis. Basic demographic and comparative analysis were performed using the Python3.8.2 software (Windows 10 64 bit, USA). RESULTS: Amongst all the states of India most respondents hailed from the top ten affected states. Overall 76.15% of doctors would either prescribe or consider prescribing hydroxychloroquine (HCQ) as prophylaxis for health-care providers (HCP). Doctors with experience of managing COVID-19 were more likely to advocate use of HCQ as prophylaxis for HCP (χ2 = 4.357, P = 0.037). Intensivists were more likely to advocate HCQ as prophylaxis (χ2 = 14.588, P < 0.001) as well as for management of mild to moderate COVID-19 (χ2 = 3.91, P = 0.048). In COVID-19, 65.8% doctors overwhelmingly preferred using anti-viral agents in severe cases, continuing ACEi/ARB (60.9%), and routinely screening for COVID-19 as a pre-operative strategy (73.85%). CONCLUSIONS: Indian doctors are largely following the scientific guidance provided by Indian National Task Force for COVID-19 and would consider prescribing HCQ as prophylaxis for COVID-19. They would also consider using it in mild to moderate COVID-19.

Increase in the risk of type 2 diabetes during lockdown for the COVID19 pandemic in India: A cohort analysis.

Lockdown due to the Coronavirus disease 2019 (COVID 19) pandemic may cause weight gain and enhance the risk of type 2 diabetes mellitus (T2DM). We aimed to determine this risk in apparently non-diabetic individuals. MATERIAL METHODS: Baseline demographic and clinical data from 100 apparently non-diabetic household members (related or unrelated) of patients with type 2 diabetes mellitus were collected until 49 days of lockdown and analyzed using the XL-STAT statistical software. A two-pronged analytical strategy was employed. First, the metabolic risk profile related to age, sex, weight, family history, and exercise pattern was analyzed. This was followed by an assessment of the risk of developing type 2 diabetes using an established risk assessment engine. RESULTS: There was a trend towards weight gain seen in 40% of the cohort, with 16% of the population experiencing a 2.1-5 kg weight increment. When all the risk parameters were analyzed together using the ADA risk engine, there was an increase in the ADA diabetes risk score in 7% of the population, with 6.66% in the high-risk group. There was a further increase in weight among 3% of the population who were already obese at baseline. CONCLUSION: We show an increased risk of T2MD consequent to weight gain during 49 days of lockdown in India.

Quantitative measure of asymptomatic cardiovascular disease risk in Type 2 diabetes: Evidence from Indian outpatient setting.

BACKGROUND: The cardiovascular (CV) risk of patients with Type 2 diabetes (T2D) of Indo-Asian descent has never been objectively assessed, although it is documented that they have a higher prevalence of CV disease (CVD). AIMS: To identify groups of Indian patients with asymptomatic T2D who are at high risk of CVD as per the QRISK calculator. METHOD: After an adequate power calculation, a nation-wide study of patients with asymptomatic T2D was conducted. The QRISK3 scores of these patients were used to derive a 10-year risk of CV events. High CVD risk was defined as ≥20% risk of CV event in 10 years. RESULTS: For a total of 1538 patients across 154 outpatient departments, the QRISK3 scores were collated. Median 10-year CVD risk was 22.2%. Mean 10-year CVD risk was 28.4% (standard deviation 22.1%), representing a 5.7-fold increase vs. controls (i.e., matched healthy adults). Absolute CVD risk increased linearly with age. Over 50% of T2D males aged above 45 years had a high (>20%) CVD risk. Women aged more than 55 years had a high risk of CVD. More than 50% of patients with a T2D duration of more than 5 years had a high risk of CVD as per the QRISK3 calculator.

Impact of complete lockdown on total infection and death rates: A hierarchical cluster analysis.

INTRODUCTION AND AIMS: Retarding the spread of SARS-CoV-2 infection by preventive strategies is the first line of management. Several countries have declared a stringent lockdown in order to enforce social distancing and prevent the spread of infection. This analysis was conducted in an attempt to understand the impact of lockdown on infection and death rates over a period of time in countries with declared lock-down. MATERIAL AND METHODS: A validated database was used to generate data related to countries with declared lockdown. Simple regression analysis was conducted to assess the rate of change in infection and death rates. Subsequently, a k-means and hierarchical cluster analysis was done to identify the countries that performed similarly. Sweden and South Korea were included as counties without lockdown in a second-phase cluster analysis. RESULTS: There was a significant 61% and 43% reduction in infection rates 1-week post lockdown in the overall and India cohorts, respectively, supporting its effectiveness. Countries with higher baseline infections and deaths (Spain, Germany, Italy, UK, and France-cluster 1) fared poorly compared to those who declared lockdown early on (Belgium, Austria, New Zealand, India, Hungary, Poland and Malaysia-cluster 2). Sweden and South Korea, countries without lock-down, fared as good as the countries in cluster 2. CONCLUSION: Lockdown has proven to be an effective strategy is slowing down the SARS-CoV-2 disease progression (infection rate and death) exponentially. The success story of non-lock-down countries (Sweden and South Korea) need to be explored in detail, to identify the variables responsible for the positive results.

Translating the statistical benefits of SGLT-2 inhibitors on cardio-renal outcomes into clinical practice.

BACKGROUND/OBJECTIVES: This study aims to analyze the positive outcomes observed in cardiovascular outcomes trials conducted with sodium-glucose co-transporter inhibitors and determine their statistical and clinical significance. METHODS: A literature search conducted using the Cochrane library resulted in five citations - randomized controlled trials (RCTs), identified for analysis. Positive cardio-renal outcomes from the five RCTs were analyzed in accordance with a pre-defined strategy which included the hierarchical flow chart, presence of a persuasive p-value (p < 0.001), and number needed to treat (NNT) estimation calculated from the absolute risk reduction (ARR) reported. RESULTS: Only four instances fulfilled these stringent criteria - reduction of cardiovascular (CV) death with empagliflozin in T2DM patients with established atherosclerotic cardiovascular disease (eASCVD) (p < 0.001; NNT 45), reduction in cardiorenal outcomes with canagliflozin in a pooled T2DM population with macroalbuminuria (p < 0.00001; NNT 22), as well as reduction in the composite of CV death or hospitalization for heart failure (hHF) (p < 0.001; NNT 30) and also reduction in hHF or CV death with dapagliflozin in T2DM with heart failure with reduced ejection fraction (HFrEF) (p < 0.001; NNT 21). CONCLUSIONS: Statistically positive outcome results must be interpreted in the context of associated clinical benefits and not in isolation.

Linear Regression Analysis to predict the number of deaths in India due to SARS-CoV-2 at 6 weeks from day 0 (100 cases - March 14th 2020).

INTRODUCTION: and Aims: No valid treatment or preventative strategy has evolved till date to counter the SARS CoV 2 (Novel Coronavirus) epidemic that originated in China in late 2019 and have since wrought havoc on millions across the world with illness, socioeconomic recession and death. This analysis was aimed at tracing a trend related to death counts expected at the 5th and 6th week of the COVID-19 in India. MATERIAL AND METHODS: Validated database was used to procure global and Indian data related to coronavirus and related outcomes. Multiple regression and linear regression analyses were used interchangeably. Since the week 6 death count data was not correlated significantly with any of the chosen inputs, an auto-regression technique was employed to improve the predictive ability of the regression model. RESULTS: A linear regression analysis predicted average week 5 death count to be 211 with a 95% CI: 1.31-2.60). Similarly, week 6 death count, in spite of a strong correlation with input variables, did not pass the test of statistical significance. Using auto-regression technique and using week 5 death count as input the linear regression model predicted week 6 death count in India to be 467, while keeping at the back of our mind the risk of over-estimation by most of the risk-based models. CONCLUSION: According to our analysis, if situation continue in present state; projected death rate (n) is 211 and467 at the end of the 5th and 6th week from now, respectively.

Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis.

INTRODUCTION: and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. MATERIALS AND METHODS: A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. RESULTS: The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. CONCLUSION: The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.