Insulin glulisine 100units/ml solution for injection 3ml cartridges

Alzheimer disease (AD) is a neurodegenerative disorder. Evidence suggests that AD shares pathophysiological similarities with type 2 diabetes. Intranasal insulin (INI) has emerged as a potential therapeutic approach for AD by directly targeting the brain and modulating insulin signaling pathways.ObjectiveTo evaluate the efficacy and safety of INI therapy for AD through a systematic review and meta-analysis of randomized controlled trials.MethodsA search of electronic databases, including PubMed, Web of Science, Scopus, and Embase, was conducted to identify relevant studies published up to June 2024. Inclusion criteria encompassed peer-reviewed original research articles focused on humans, investigating the therapeutic effects of INI administration on cognitive impairment associated with AD, and reporting quantitative data on cognitive outcomes, biomarkers, or pathological markers relevant to AD. A meta-analysis was conducted to quantitatively synthesize the effects of INI on cognitive outcomes.ResultsA total of 647 articles were identified, and eight studies met the inclusion criteria. The overall odds ratio was 3.75 (95%CI 1.49-9.40). The test for overall effect showed a statistically significant difference (p2 value indicated a high level of heterogeneity (85.5%), suggesting significant variability among the studies.ConclusionWhile the current data is not yet conclusive enough to definitively establish INI as a standard treatment for AD, the evidence supporting its safety, efficacy, and reduced risk of systemic side effects suggests potential cognitive benefits for improving global cognition in patients with AD.

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Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia. Recent studies have identified microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, as modulators of pathways involved in T2DM pathophysiology. Dysregulated miRNA expression has been detected in various samples collected from patients with T2DM, implicating these molecules in disease onset and progression. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: "miRNA AND gliclazide", "miRNA AND glibenclamide", "miRNA AND gliquidone", "miRNA AND glimepiride", "mirRNA AND metformin", "miRNA AND pioglitazone", "miRNA AND rosiglitazone", "miRNA AND sitagliptin", "miRNA AND vildagliptin", "miRNA AND alogliptin", "miRNA and saxagliptin", "miRNA AND linagliptin", "miRNA AND liraglutide", "miRNA and dulaglutide", "miRNA AND semaglutide", "miRNA AND tirzepatide", "miRNA AND lixisenatide", "miRNA AND empagliflozin", "miRNA AND dapagliflozin", miRNA AND insulin glargine", "miRNA AND insulin detemir", "miRNA AND insulin degludec", "miRNA AND insulin aspart", "miRNA AND insulin glulisine", and "miRNA AND insulin lispro". Additionally, gray literature was searched in ClinicalTrials.gov, the EU Clinical Trials Register (EudraCT), and the ISRCTN Registry to identify unpublished studies. Studies were eligible for inclusion if they were clinical interventional studies assessing the impact of currently available antidiabetic treatments on miRNA expression. Only articles published in English were considered. The risk of bias was evaluated using the RoB2 (Risk of Bias 2) and ROBINS-I (Risk Of Bias In Non-randomized Studies-of Interventions) tools. Study characteristics and major findings were tabulated. Results: A total of 1263 manuscripts was identified initially. After removing duplicates, 726 articles remained for further screening. Ultimately, 17 manuscripts reporting interventional clinical trials on the effects of antidiabetic treatment on miRNA were included, encompassing a total of 1093 patients. Key findings included treatment-associated changes in miRNA expression and their potential utility for the prediction of clinical outcomes. Conclusions: Current evidence supports the hypothesis that antidiabetic treatments modulate miRNA expression, with some findings showing predictive value for metabolic outcomes. However, the available data remain limited and of low grade of certainty, and further large-scale clinical studies are needed to provide deeper insights into these associations.

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Dear Editor: Further data regarding the use of specific insulins for continuous subcutaneous insulin infusion (CSII) are always of interest because of the relative paucity of research in this area. As such, the recent article by van Bon et al.1 is of particular value. However, we consider that some of the conclusions, as presented by the authors, deserve greater scrutiny. First, according to the methods, this was a randomized, controlled, open-label, crossover clinical trial designed to show the superiority of insulin glulisine over both insulin aspart and insulin lispro. For the primary outcome (unexplained hyperglycemia and/or perceived perfusion set occlusion), a numerically greater percentage of patients reported this outcome with glulisine (68.4%) compared with either aspart (62.1%) or lispro (67.3%). The authors refer to a lack of statistical significance (P=0.04 for glulisine vs. aspart, P=0.03 for glulisine vs. lispro) for this outcome, implying little to no difference among the three insulins, rather than as a failure to show superiority (which was what the study was powered to detect). Furthermore, there were significant differences among the three insulins in the secondary outcomes of monthly rate of unexplained hyperglycemia or perceived infusion set occlusion, rate of significant hyperketonemia and/or hyperketonemia at risk of ketosis, and rate of symptomatic and nocturnal hypoglycemia. These results seem to belie the conclusions of the authors that there were no significant differences among the three insulins when used in CSII. I would also question the authors' suggestions that a trend toward greater occurrence of unexplained hyperglycemia and perceived infusion set occlusion seen in this study with insulin glulisine compared with insulin aspart and lispro should be taken as balancing the results from the previous study by Hoogma and Schumicki2 in which the opposite trend was seen. As the previous study was not statistically powered to detect superiority for this outcome, whereas the study by van Bon et al.1 was explicitly designed to do so, these results should instead override the previous findings. Second, the article describes various post hoc analyses that were carried out on the final data set but that had not previously been planned or described in the study design. There appears to be no well-defined reason for these additional statistical analyses, and I would query their relevance and utility. The relative value of any results produced by such analyses must be considered of lesser weight than the main study as cohort numbers were not chosen with these in mind, and thus the statistical power may not be sufficient to show a true difference. Third, the authors place a large amount of emphasis on the results relating to time to change infusion set, stressing the point that less difference was seen in occurrence of occlusion between glulisine and aspart or lispro when sets were changed more frequently. This finding is of questionable clinical relevance when compared with the observation that the timings seen in this study, with patients changing catheters much less frequently than advised, are much more likely to be applicable to a real-world scenario than a rigidly enforced limit of every 2 days. Following the results of this study, it seems that patients using glulisine in infusion sets should be instructed to change their infusion sets every 2 days. This requirement for more frequent changes could be due to a lower chemical and physical stability of glulisine compared with lispro and aspart, presenting challenges in the pump setting. Finally, the authors suggest that the increased frequency of hypoglycemia seen with glulisine could be the result of slight overdosing of glulisine throughout this study. They refer to previous studies in which patients have required a lower basal dose of glulisine than other insulins. In this current study, although initial dosage was based on the patient's dose at trial commencement, dosing adjustments for each of the study insulins were based on each patient's glucose control in line with recommendations from the American Diabetes Association. If the glulisine dose was high enough to lead to increased hypoglycemic events, it could be expected that average glycosylated hemoglobin levels in these patients would be decreased compared with aspart and lispro. Throughout the study, glycemic control remained stable across all three treatment groups with no differences observed between glulisine and aspart or glulisine and lispro. Instead of stating in the conclusion that “all three short-acting insulin analogs could be used in CSII as no difference was seen among GLU, ASP, and LIS on the primary outcome measure..,” the authors should have reported that glulisine failed to show superiority over either aspart or lispro, countering the trend seen in the previous trial of Hoogma and Schumicki,2 and was inferior with regard to several of the outcomes investigated.

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BackgroundThe relationship between antidiabetic drugs and thromboembolic events remains unclear. The FDA Adverse Event Reporting System (FAERS) data was used to systematically assess safety signals and polypharmacy-related drug-drug interactions of antidiabetic medications.MethodsBy analyzing FAERS reports from 2004 to 2025 that included antidiabetic drugs, the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Information Component (IC), and the Empirical Bayes Geometric Mean (EBGM) were used to assess disproportionality. Factors such as the main suspected drug, event seriousness, age, sex, US origin, and the recent reporting period were examined in sensitivity analyses. Drug-drug interactions (DDIs) were evaluated using the Ω shrinkage measure and adjusted for false discovery rate.ResultsWe analyzed 81,280,515 FAERS reports from 2004-2025, of which 498,750 (0.61%) involved at least one of 30 antidiabetic drugs, revealing strong arterial thromboembolic signals for rosiglitazone (IC = 4.68), gliclazide (IC = 1.55), linagliptin (IC = 1.56), dapagliflozin (IC = 1.25), and several DPP-4 inhibitors. Only insulin degludec (IC = 0.73, IC025 = 0.61) and insulin aspart (IC = 0.28, IC025 = 0.21) showed nominal venous thromboembolic signals. For GLP-1 agonists, no thromboembolic signals were detected. These observations were confirmed by sensitivity analyses across all subgroups. Moreover, 257 significant drug-drug interactions were identified, particularly between insulin analogues and simvastatin, acetaminophen, or gabapentin.ConclusionDPP-4 inhibitors, SGLT2 inhibitors, and certain insulins showed positive arterial thromboembolic signals. No positive thromboembolic signals were detected for GLP-1 agonists, consistent with their favorable cardiovascular safety profile observed in randomized controlled trials. Numerous significant drug-drug interactions were also detected, particularly for insulin analogues with other drugs. Further research is necessary to understand the clinical importance of these interactions.

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