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Introduction: Semaglutide, a glucagon-like peptide 1 receptor agonist (GLP1RA), is available in both parenteral and oral preparations. Studies of injectable preparations have convincingly demonstrated its beneficial effect on major adverse cardiac events (MACE). This predictive analysis was undertaken to forecast early termination of the SOUL trial (oral semaglutide) as well as the primary events. Methods: SOUL is a multicenter, double-blind, placebo-controlled randomized controlled trial (RCT) evaluating the reduction in MACE associated with oral semaglutide versus placebo in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. A sample of 9642 participants will be followed for 5 years and 5 months. A random-effects model meta-analysis, pooling hazard ratios from previous RCTs, was conducted using R software to inform the predictive model. The background CV event rates from the placebo arms of previous RCTs with semaglutide were matched with the pre-adjudicated assumptions of the SOUL trial to create the predictive model. The truncated trial duration, MACE, and its individual components in the intervention and placebo arms were estimated. The predicted difference between the two groups was estimated using the chi-squared test. Results: A pooled analysis of 10,013 patients revealed a significant reduction in the number of MACEs associated with semaglutide (HR 0.79, 95% CI 0.69–0.91). Predictive analysis indicated that 1225 events would be achieved by 3.78 years, suggesting premature termination. Conclusion: The mathematical model based on the meta-analysis predicts that the SOUL study on oral semaglutide will be terminated early, with oral semaglutide showing benefits in terms of MACE compared to placebo. If the SOUL study corroborates the findings of this model, it may not only form the basis for the calculation of power but also define the duration of such studies, reducing costs and easing the process of designing cardiovascular outcome trials (CVOTs). Protocol Registration: INPLASY202460061. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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 metaanalysis. 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. [ABSTRACT FROM AUTHOR]

Traditionally, treatment for type 2 diabetes (T2D) centered on the failure of insulin secretion from the beta cells of the pancreas and insulin resistance. Though effective in certain respects, these treatments are marred by multiple undesirable side effects. The discovery of the incretin defect and the role of glucagon in T2D shifted the focus to therapies that addressed not only the beta cell defect but also the alpha cell defect in the pancreas. Therapies addressing these defects, simultaneously, have switched the entire focus of T2D therapy by not only improving glycemic control but also reducing the risk of hypoglycemia and weight gain and improving outcomes. These newer modalities of treatment started off with dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RAs), and now further treatments in the form of twincretins (GLP1/GIP dual agonists) and triple agonists (GLP1/GIP/glucagon agonists) are unraveling. This article provides a summary of the evidence available with these newer antidiabetics, which address the glucagon defect in T2D. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, t ² : < 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, t ² : < 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. [ABSTRACT FROM AUTHOR]

Objective: There are no major head-to-head comparative studies till date to compare the differences in glycemic efficacy, safety, or cardio-renal effects within SGLT2 inhibitors. This survey was conducted to understand the different parameters that clinicians identify while choosing an SGLT2 inhibitor in routine clinical practice. Materials and methods: A cross-sectional questionnaire-based survey of healthcare professionals (HCP) was conducted across India. Data were analyzed and expressed as descriptive statistics. Results: In clinical practice, the majority of HCPs identified a history of cardiovascular disease (CVD) as the most important factor for prescribing SGLT2 inhibitors in patients with T2DM. The majority of HCPs opined that among all the SGLT2 inhibitors, canagliflozin had the strongest effect on HbA1c reduction (56%), reduction in body weight (59%), and renal benefit (66%), whereas empagliflozin was associated with CV benefits (48%). In terms of heart failure, canagliflozin, empagliflozin, and dapagliflozin were similarly preferred. Conclusions: This survey gives us an understanding of the current clinical practice prevalent among Indian physicians as far as the prescription pattern of SGLT2 inhibitors is concerned. [ABSTRACT FROM AUTHOR]

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%5frecord.php?ID=CRD42021268564 ], PROSPERO 2021 CRD42021268564. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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). Statistically positive outcome results must be interpreted in the context of associated clinical benefits and not in isolation. [ABSTRACT FROM AUTHOR]

Introduction: Although the positive effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on hospitalization for heart failure in type 2 diabetes (T2D) seem definite, some doubt exists about their effects on atherosclerotic cardiovascular disease (ASCVD). This study aims to shed light on this debatable issue. Methods: An electronic database search (Cochrane Library, PubMed and Embase) was performed using two groups of terms ["sodium glucose cotransporter2 inhibitor", "dapagliflozin", "canagliflozin", "empagliflozin", "ertugliflozin"] AND ["major adverse cardiac events", "MACE", "cardiovascular death or hospitalization for heart failure", non-fatal myocardial infarction", "non-fatal stroke", "cardiovascular death", "hospitalization for heart failure"] and the cardiovascular outcome trials (CVOT) and pre-approval studies in phase 3 of all the SGLT2i analysed using comprehensive meta-analysis (CMA) software, version 3, Biostat Inc., Englewood, NJ, USA. Results: Analysis of the CVOT revealed that the hazard ratio of the pooled effect size for MACE was statistically significant (HR 0.89, 95% CI 0.83–0.96, P = 0.002). There was a significant reduction in non-fatal myocardial infarction (MI) (HR 0.87, 95% CI 0.78–0.97, P = 0.01), but no improvement was seen for non-fatal stroke (HR 1.01, 95% CI 0.89–1.16, P = 0.83). The pooled analysis of this end point showed statistically significant reduction of the composite of CV death or hospitalization for heart failure (hHF) (HR 0.76, 95% CI 0.67–0.87, P < 0.001) and hHF (HR 0.69, 95% CI 0.61–0.79, P < 0.001), but not for CV death alone (HR 0.82, 95% CI 0.64–1.05, P = 0.11). The meta-analysis of the events in the pooled analysis of the phase 3 trials reveals that the hazard ratio for MACE was statistically nonsignificant (HR 0.83, 95% CI 0.66–1.03, P = 0.10). There was a 34% statistically significant reduction in MI (95% CI 0.48–0.91, P = 0.01), a 36% statistically significant reduction in CV death (95% CI 0.41–0.97, P = 0.04) and a 64% statistically significant reduction in hHF (95% CI 0.18–0.69, P < 0.01). In contrast, there was a 17% statistically nonsignificant increased risk of stroke (95% CI 0.80–1.70, P = 0.40). Conclusion: The predominant impact of SGLT-2i is on "hHF or CV mortality" composite driven predominantly by reduction in hHF and not atherosclerotic CV disease. [ABSTRACT FROM AUTHOR]

The current diabetes management strategies not only aim at controlling glycaemic parameters but also necessitate continuous medical care along with multifactorial risk reduction through a comprehensive management concept. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of evolving antidiabetic agents that have the potential to play a pivotal role in the comprehensive management of patients with diabetes due to their diverse beneficial effects. SGLT2i provide moderate glycaemic control, considerable body weight and blood pressure reduction, and thus have the ability to lower the risk of macrovascular and microvascular complications. Some of the unique characteristics associated with SGLT2i, such as reduction in body weight (more visceral fat mass loss than subcutaneous fat loss), reduction in insulin resistance and improvement in β-cell function, as measured by homeostatic model assessment-β (HOMA-β) could be potentially beneficial and help in overcoming some of the challenges faced by Indian patients with diabetes. In addition, a patient-centric approach with individualised treatment during SGLT2i therapy is inevitable in order to reduce diabetic complications and improve quality of life. Despite their broad benefits profile, the risk of genital tract infections, volume depletion, amputations and diabetic ketoacidosis associated with SGLT2i should be carefully monitored. In this compendium, we systematically reviewed the literature from Medline, Cochrane Library, and other relevant databases and attempted to provide evidence-based recommendations for the positioning of SGLT2i in the management of diabetes in the Indian population. Funding: AstraZeneca Pharma India Limited. [ABSTRACT FROM AUTHOR]

Background: This 26-week, open-label observational study assessed the incidence and type of adverse events (AEs) associated with liraglutide use according to the standard clinical practice settings and the local label in India. Materials and Methods: A total of 1416 adults with type 2 diabetes (T2D) treated with liraglutide in 125 sites across India were included in the study. Participants were newly diagnosed or already receiving antidiabetic medications. Safety and efficacy data were collected at baseline and at approximately weeks 13 and 26. The primary outcome was incidence and type of AEs while using liraglutide, with events classified by Medical Dictionary for Regulatory Activities system organ class and preferred term. The secondary objective was to assess other clinical parameters related to effective T2D management. Results: Twenty AEs, predominately gastrointestinal, were reported in 1.3% of the study population in scheduled visits up to week 26. No serious AEs, including death, were reported. Hypoglycemic episodes were reported in 7.3% of participants at baseline and 0.7% at week 26. No major hypoglycemic events were reported up to week 26 (baseline: 0.4%). Glycated hemoglobin was reduced from baseline (8.8 ± 1.3%) to week 26 by 1.6 ± 1.1% (P < 0.0001); significant improvements in fasting blood glucose, and 2-h postprandial blood glucose (post-breakfast, -lunch, and -dinner) were also observed. Mean body weight decreased by 8.1 ± 6.5 kg from baseline (92.5 ± 14.6 kg; P< 0.0001). Conclusions: From the number of AEs reported, it is suggested that liraglutide was well tolerated in subjects with T2D treated under standard clinical practice conditions in India. Liraglutide was effective, and no new safety concerns were identified. [ABSTRACT FROM AUTHOR]

The issue related to macrovascular outcomes and intensive glycemic control was hotly debated after the publication of landmark trials like ACCORD, ADVANCE, and VADT. The only benefits seem to come from intervening early on in the disease process as indicated by the 10-year UKPDS follow-up. To complicate matters USFDA made it mandatory for modern drugs to conduct cardiovascular safety trials in high-risk populations after the 2008 rosiglitazone scare. This led to all the modern group of drugs designing cardiovascular safety trials (gliptins, GLP-1 agonists, and SGLT-2 inhibitors) to meet USFDA regulatory requirements. We saw publication of the first 2 randomized trials with gliptins published a year and a half back. On the face value SAVOR TIMI and EXAMINE satisfied the primary composite CV end-points. However, issues related to significant increase in heart failure and all-cause 7-day on-treatment mortality created a lot of confusion. FDA reanalysis of these data (especially SAVOR) raises a lot of doubts as far as CV safety of these groups of drugs was concerned. Hence, all eyes were on TECOS, which was published this year. We take a microscopic look at these trials trying to understand where we stand as from now on this issue. [ABSTRACT FROM AUTHOR]

Aim: To explore the clinical safety and effectiveness of insulin detemir (IDet) in a subgroup of Indian patients with type 2 diabetes (T2D) switched from either insulin glargine (IGlar) or neutral protamine Hagedorn (NPH) insulin in the 24-week, non-interventional A1chieve study. Materials and Methods: Indian patients with T2D switching from pre-study IGlaror NPH insulin to IDet were included. Safety and effectiveness outcomes were evaluated by the physicians in local clinical settings. Results: A total of 102 patients switched from IGlar to IDet (GLA group) and 39 patients switched from NPH insulin to IDet (NEU group). At baseline, the mean glycated hemoglobin A1c (HbA1c) levels were 9.9 ± 1.8% in the GLA group and 9.1 ± 1.2% in the NEU group. No serious adverse drug reactions, serious adverse events, or major hypoglycemic events were reported in either group throughout the study. At baseline and Week 24, 11.8% and 7.5% of patients, respectively, reported overall hypoglycemic events in the GLA group. No hypoglycemic events were reported at Week 24 in the NEU group. At Week 24, the mean HbA1c levels were 7.6 ± 0.9% in the GLA group and 7.3 ± 0.7% in the NEU group. The mean fasting plasma glucose, postprandial plasma glucose and quality of life also appeared to improve over 24 weeks. Conclusion: Switching to IDet therapy from IGlar and NPH insulin was well-tolerated and appeared to be associated with improved glycogenic control in Indian patients. [ABSTRACT FROM AUTHOR]

In an island situation when a group of individuals belonging to different cultural, linguistic and religious backgrounds come in close contact as a result of their forced confinement their survival instinct and their biological, social and economic needs hold them together. The paper attempts to understand the historical process of societal and cultural transformation through which the people born in Port Blair, Andaman Islands, emerged as a vibrant community. The process is best explained in terms of 'cultural creolisation' drawing analogy from Dell Hymes' (1971) notion of the 'creolisation of language'. A 'pidgin' is formed in a contact situation, which in the course of time becomes a 'creole'. This paper deals with the descendents of ex-convicts, who were released from the confinement of their walled cells once they served the term but were never permitted to leave the island. So they married with whomeveravailable resulting in mixed families of Malayalam speaking Muslim husband from Kerala, a Hindu Bengali-speaking wife from erstwhile East Bengal, and a Punjabi Sikh daughter-in-law. The sheer necessity of day to day living forced them to evolve a pidgin which over years became their common language. [ABSTRACT FROM AUTHOR]

Insulin therapy is not without side effects. In patients with complications on complex regimens, failure to attain adequate glycemic control exposes the patient to high risks and the considerable mental distress associated with failed injectable therapy. As clinicians, we felt it necessary to undertake a trial of newer therapies like insulin degludec, which according to published literature, appears to be superior to earlier basal analogs by fewer hypoglycemic episodes, better glycemic predictability, and genuine 24-hour coverage. Here we report on three cases seen in our own clinical practice where insulin degludec was used in patients experiencing inadequacies with their current basal insulin therapy (insulin glargine). Switching to insulin degludec resulted in clinically meaningful reductions in hypoglycemia, along with reduced fasting plasma glucose and glycosylated hemoglobin and improved satisfaction with treatment. We also explored the use of long-acting insulin in renal failure and the possibility of dose reduction when switching from existing basal insulin therapy. [ABSTRACT FROM AUTHOR]

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols. [ABSTRACT FROM AUTHOR]

The present study is an attempt to examine the Koli fishermen, a fishing community of Maharashtra, in the specific eco-cultural surroundings of their traditional maritime environment. The enquiry has been centered on primarily to an understanding of their traditional knowledge system pertaining to the management of sea resource. The study was conducted at Alibag, a small coastal fishing town on Arabian Sea in the Raigarh district of Maharashtra. The Kolls possess a unique knowledge of their immediate environment, sea topography and fish behaviour which is classified as their cognitive taxonomic categories. Social organisation of fishing and division of labour in fishing are suitably adjusted to their specific nature of marine fishing methods and techniques for getting optimum result. [ABSTRACT FROM AUTHOR]

Highlights from the article: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Dovepress Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 202.164.43.126 on 06-Aug-2019 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Dovepress Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 202.164.43.126 on 06-Aug-2019.

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. [ABSTRACT FROM AUTHOR]