Efficacy and safety of once-weekly insulin icodec in type 2 diabetes: A meta-analysis of ONWARDS phase 3 randomized controlled trials.

AIM: Insulin icodec is a novel ultra-long action basal insulin analogue designed for once-weekly administration. With the merit of once-a-week administration, it promises better adherence and greater treatment satisfaction because of reduced injection frequency. The purpose of this study was to ascertain the efficacy and safety of once-weekly insulin icodec in comparison with other basal insulin analogues in the management of type 2 diabetes. MATERIALS AND METHODS: The PRISMA guidelines were followed during the conduct of this study. For the eligible studies, five databases and ClinicalTrials.gov were screened until July 2023. All randomized controlled trials comparing the efficacy and safety of insulin icodec in type 2 diabetes versus other insulin analogues were included. The extracted data were then analysed for meta-analysis using RevMan 5.3 software. RESULTS: Five clinical trials with 3764 participants were included. The meta-analysis showed that once-weekly insulin icodec had higher glycated haemoglobin (HbA1c) reduction [mean difference -0.17%, 95% confidence interval (CI; -0.28 to -0.06), p = .003], with no significant difference in fasting plasma glucose compared with other insulin analogues. HbA1c achievement <7% [odds ratio 1.51, 95% CI (1.14-1.99), p = .004] and HbA1c achievement <7% without hypoglycaemia [odds ratio 1.45, 95% CI (1.26-1.67), p < .00001] were observed in higher proportions with insulin icodec compared with the comparator group. The percentage of time spent in the target glycaemic range was comparatively similar between insulin icodec and the comparator [mean difference 2.42%, 95% CI (0.01-4.84), p = .05]. There was a significantly higher incidence of level 1 hypoglycaemia with insulin icodec but no significant difference was seen for the incidence of levels 2, 3 and combined 2/3 hypoglycaemia. Any adverse events and adverse events related to basal insulin were comparably similar in insulin icodec and comparators. The subgroup analysis of once-weekly insulin icodec with individual insulin analogues (glargine U100 and degludec) showed that insulin icodec had similar efficacy with insulin glargine U100 but superior efficacy with higher HbA1c reduction with insulin icodec compared with insulin degludec. The safety profile was comparable between insulin icodec and glargine U100, whereas insulin icodec reported higher incidence of hypoglycaemia events and any adverse events when compared with degludec. CONCLUSION: Once-weekly insulin icodec showed a better HbA1c reduction with a higher proportion of patients achieving HbA1c targets in comparison with once-daily basal insulin analogues. They were no major safety concerns with respect to hypoglycaemia or adverse events.

Acute and sub-chronic toxicity of Liberin, an anti-diabetic polyherbal formulation in rats.

BACKGROUND: The polyherbal formulation (PHF) liberin, is known to exert anti-hyperglycemic effects in type 2 diabetes mellitus. Hence, it is important to study the safety profile of PHF in the current study through acute and chronic toxicity evaluation. OBJECTIVES: This research aims to assess the acute and sub-chronic toxicity of PHF in rats. MATERIALS AND METHODS: PHF was administered once orally (1000 mg/kg body weight), and the rats (male and female) were monitored for toxicity signs for a 14-day period. For a 28-day chronic toxicity study, rats were daily administered with PHF dose of 500 mg/kg and 1000 mg/kg body weight. Rats were followed up for mortality, weight changes, and other morbidities. Further haematological, biochemical, and histopathological changes were assessed. RESULTS: No death related to treatment or toxicity signs were recorded in the acute single-dose administration group. The results showed that the PHF was tolerated well up to a dose of 1000 mg/kg body weight. Even at the high dose of 1000 mg/kg body weight, sub-chronic tests did not show any significant difference between the dosed and normal groups. No significant changes were seen in the histopathological analysis of the liver, spleen, and kidney as well as haematological and biochemical parameters in acute, sub-chronic and satellite groups following the administration of PHF. CONCLUSION: The results confirmed that there was no adverse effect of this PHF at the maximum dose of 1000 mg/kg body weight in Wistar rats. Further, no adverse delayed effects related to PHF were observed in the satellite group. Therefore, this PHF appears safe for therapeutic purposes in the Ayurvedic medicinal system.

Anthropometric Indices and Type 2 Diabetes Mellitus as a Risk Factor in Predicting Nonalcoholic Fatty Liver Disease - A Prospective Study in Indian Population.

Background: The different anthropometric indices have different predictive values of nonalcoholic fatty liver disease (NAFLD) in various populations. Since obesity is a common cause of NAFLD and diabetes, therefore, it is critical to correlate the various anthropometric indices as a risk factor in terms of NAFLD and diabetes in the Indian population. In view of reported association between obesity and NAFLD, the study was employed to analyze the relationship of various anthropometric indices (body mass index [BMI], a body shape index [ABSI], waist-height ratio [WHtR], etc.) with NAFLD and to comment, if possible, which among them has the highest predictive value in patients with type 2 diabetes. Material and Methods: Data of 220 diabetic patients (36-80 years) were analyzed. Anthropometric data were collected using standard methods. Routine biochemical investigations data were used. Ultrasonography was used to assess liver status for NAFLD. Results: Based on the results, Waist height ratio [WHtR] and BMI had better correlation with NAFLD than ABSI. The desirable WHtR cutoff value was 0.545 with 62% of sensitivity and 62% of specificity. The cut off for BMI and ABSI were 24.6 and 0.805, respectively, with 65% of sensitivity and 62% of specificity for BMI and 63% of sensitivity and 42% of specificity for ABSI. Conclusion: There is a strong association of BMI and ABSI with NAFLD in this study. Public health measures to limit overnutrition and management of obesity are essential to prevent NAFLD, and as its negative health effects on type 2 diabetes mellitus.

The mechanistic role of neutrophil lymphocyte ratio perturbations in the leading non communicable lifestyle diseases.

Inflammation plays a critical role in the development and progression of chronic diseases like type 2 diabetes mellitus, coronary artery disease, and chronic obstructive pulmonary disease. Inflammatory responses are indispensable for pathogen control and tissue repair, but they also cause collateral damage. A chronically activated immune system and the resultant immune dysregulation mediated inflammatory surge may cause multiple negative effects, requiring tight regulation and dampening of the immune response to minimize host injury.  While chronic diseases are characterized by systemic inflammation, the mechanistic relationship of neutrophils and lymphocytes to inflammation and its correlation with the clinical outcomes is yet to be elucidated. The neutrophil to lymphocyte ratio (NLR) is an easy-to-measure laboratory marker used to assess systemic inflammation. Understanding the mechanisms of NLR perturbations in chronic diseases is crucial for risk stratification, early intervention, and finding novel therapeutic targets. We investigated the correlation between NLR and prevalent chronic conditions as a measure of systemic inflammation. In addition to predicting the risk of impending chronic conditions, NLR may also provide insight into their progression. This review summarizes the mechanisms of NLR perturbations at cellular and molecular levels, and the key inflammatory signaling pathways involved in the progression of chronic diseases. We have also explored preclinical studies investigating these pathways and the effect of quelling inflammation in chronic disease as reported by a few in vitro, in vivo studies, and clinical trials.

Effectiveness of polyherbal formulations for the treatment of type 2 Diabetes mellitus - A systematic review and meta-analysis.

BACKGROUND: The mortality and morbidity rate of diabetes patients is increasing worldwide which requires an ideal treatment to prevent the disease worsening. Traditional medicine is gaining more attention in diabetes due to its efficacy and safety. We, therefore performed a systematic review study of clinical trials to assess the comparative effect of polyherbal formulations in type 2 Diabetes mellitus. OBJECTIVES: To find the effectiveness of polyherbal formulations in blood sugar and lipid level for type 2 Diabetes mellitus. MATERIAL AND METHODS: PubMed, Scopus and CINAHL databases for clinical trials investigating the effect of polyherbal formulations in Type 2 Diabetes mellitus patients were searched. Meta-analysis of eligible trials was conducted employing Revman 5.2 software. RESULTS: Fourteen randomized controlled trials were found eligible for meta-analysis. Meta-analysis of findings showed a significant effect of polyherbal formulations on blood sugar level compared to control group. The estimated standard mean changes at 95% confidence interval, following polyherbal formulations treatment were -0.59, (-0.91 to - 0.27) mg/dL; for fasting blood sugar(p < 0.001), -0.69, (-1.18 to -0.21) mg/dL; for postprandial blood sugar (p = 0.005) and -0.46, (-0.88 to -0.04) gm%; for glycated haemoglobin (p = 0.03). The reduction in postprandial sugar and glycated haemoglobin was statistically significant with polyherbal formulations compared to metformin treatment but not for fasting sugar. Similarly in lipid profile the reduction for total cholesterol and triglycerides was statistically significant with polyherbal formulations compared to control group but was not significant for HDL and LDL whereas in other group of polyherbal formulations and metformin only HDL was favouring polyherbal formulations. CONCLUSION: Polyherbal formulations occurred to be effective in lowering blood sugar level in Type 2 diabetes but their further efficacy in managing diabetes needs to be validated. Therefore, a qualitative, long term, randomized placebo-controlled trials of adequate sample size are necessary to determine the efficacy of polyherbal formulation in managing diabetes.

Serum paraoxonase 1 activity status in patients with liver disorders.

BACKGROUND/AIM: Paraoxonase 1 (PON1) is an esterase, exclusively synthesized by liver. The present study has two objectives: to determine the PON1 activity status in various disorders associated with hepatocellular damage and to correlate the changes of PON1 activity with the standard liver function and fasting lipid profile tests in these disorders. PATIENTS AND METHODS: The study groups consisted of 95 patients with liver diseases including acute viral hepatitis (14), cirrhosis with portal hypertension (33), leptospirosis (14), sepsis and multi organ failure (15), left ventricular failure (9), and falciparum malaria (10); and 53 healthy controls. Serum PON1 activity was measured manually using spectrophotometer. Liver function test parameters and fasting lipid profile were performed in clinical chemistry auto analyzer (Hitachi 912). RESULTS: The serum PON1 activity in patients with acute viral hepatitis and sepsis decreased significantly ( P < 0.001) and moderately in falciparum malaria ( P < 0.05). However, in patients with cirrhosis, leptospirosis and left ventricular patients, its activity did not change significantly. On applying Pearson correlation, serum PON1 activity correlated positively with high-density lipoprotein-cholesterol (HDL-C) in patients with sepsis (r=0.633, P < 0.05), left ventricular failure patients (r=0.814, P < 0.05) and negatively with acute viral hepatitis patients (r=-0.528, P <0.05). CONCLUSION: PON1 activity has decreased significantly in acute viral hepatitis, sepsis with multi organ failure and falciparum malaria patients. Determination of PON1 activity may serve as a useful additional test in assessing these conditions.