Background: Dapagliflozin is effective and well-tolerated in type 2 diabetes mellitus (T2DM) patients and is often combined with metformin in clinical practice, with or without other antidiabetic agents. Yet, real-world data on the safety of the combined use of dapagliflozin and metformin are limited. Methods: The DONATE study assessed the safety of dapagliflozin in 2,990 Chinese T2DM patients who received ≥1 dose of dapagliflozin. This post-hoc analysis assessed the incidences of adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) during the 24-week follow-up in patients receiving both dapagliflozin and metformin, with or without other antidiabetic agents. Results: In total, 2,165 patients (72.4%) from the DONATE study received both dapagliflozin and metformin. Comparable with that observed in the overall population, of these patients, 780 (36.0%) had ≥1 AE: 197 (9.1%) were drug-related as judged by the investigator, 129 (6.0%) were serious, and 96 (4.4%) resulted in treatment discontinuation. Urinary tract infections (UTIs), genital tract infections (GTIs) and hypoglycaemia developed in 50 (2.3%), 32 (1.5%), and 23 (1.1%) patients, respectively. In patients receiving dapagliflozin and metformin without other antidiabetic agent (n=322), 86 (26.7%) had ≥1 AE: 12 (3.7%) were drug-related as judged by the investigator, 8 (2.5%) were serious, and 6 (1.9%) resulted in treatment discontinuation. UTIs, GTIs, and hypoglycaemia developed in 4 (1.2%), 2 (0.6%), and 1 (0.3%) patient, respectively. The incidences of AEs, SAEs, and AESIs were also low when dapagliflozin and metformin were used together with dipeptidyl peptidase-4 inhibitor (DPP-4i, 37.5%, 3.1%, and 6.9%) or insulin (36.5%, 7.1%, and 5.0%). Conclusion: The combined use of dapagliflozin and metformin, with or without other antidiabetic agents such as DDP-4i or insulin, showed a good safety profile in Chinese T2DM patients in the real world. Disclosure L. Guo: None. J. Wang: None. L. Li: None. L. Yuan: None. S. Chen: None. H. Wang: None. T. Li: None. L. Qi: None. H. Yang: None.
After insecticides are used in the field, their toxicity will gradually decrease to sublethal concentration with the passage of time and environmental factors, and some pest individuals will be exposed to sublethal concentrations, which will result in the sublethal effects. Therefore, understanding the sublethal effects of pesticides is the key to examine their efficacy and evaluate pesticide risk management. Panonychus citri McGregor (Acari: Tetranychidae) is a key citrus pest in the world and its control is largely based on the use of acaricides, such as spirobudiclofen In this study, the sublethal effects of spirobudiclofen on population parameters of Panonychus citri adult females were evaluated. The results showed that sublethal concentration of spirobudiclofen significantly reduced in the longevity and fecundity of female adults, and the effects increased with increasing tested concentrations (LC30, LC50). In order to characterise the spirobudiclofen molecular mechanism, the transcriptomes and metabolomics of spirobudiclofen-treated (two sublethal concentrations LC30 and LC50) and untreated adult females were compared using RNA-sequencing and LC-MS. The RNA-seq results revealed that the immune defense, antioxidative system, cuticle formation and lipid metabolic pathway of P. citri were involved in the responses to spirobudiclofen stress. Moreover, based on the disordered lipid metabolic pathways obtained from transcriptomic studies, the sublethal effects of spirobudiclofen on P. citri were examined by LC-MS; the results showed that the tolerance metabolism of P. citri exposed to spirobudiclofen was regulated by enhancing the metabolism of glycerophospholipid and glycine, serine and threonine. In the present study, transcriptomics and metabolomics-based approaches were employed to examine the molecular mechanism of spirobudiclofen-induced sublethal effects on P. citri, and the results provide new insights into the defense mechanisms at the molecular and biochemical level, and valuable information for pest control strategy development.
Background: Dapagliflozin significantly improves glycemic control, body weight and blood pressure in Asian patients with type 2 diabetes mellitus (T2DM) , but safety data from studies with a large population are lacking. The DONATE study investigated the real-world safety of dapagliflozin in Chinese patients with T2DM. Methods: This observational study enrolled patients with T2DM from 88 hospitals in China, who had received ≥1 dose of dapagliflozin between August 2017 and July 2020. Patients were followed for 6 months, or 7 days after discontinuing study drug. Primary outcome was the incidence of adverse events (AEs) and serious adverse events (SAEs) , particularly urinary tract infections (UTIs) , genital tract infections (GTIs) and hypoglycemia. Exploratory outcomes included the incidence of AEs of specific interest (AESI) and absolute changes in metabolic factors. Results: Of 3000 patients enrolled, 2990 patients were included in the safety analysis set; 1059 (35.4%) reported ≥1 AE, including 186 (6.2%) with ≥1 SAE. Adverse drug reaction was reported in 268 (9.0%) patients. In total, there were 70 (2.3%) , 39 (1.3%) and 32 (1.1%) patients with UTI, GTI and hypoglycemia, respectively. The occurrence of other AESIs was also low: polyuria (0.7%) , volume depletion (0.3%) , renal impairment (0.3%) , hepatic impairment (0.2%) , haematuria (0.2%) and diabetic ketoacidosis (0.1%) . There were no abnormal electrolytes events reported. At Week 24 (metabolic analysis set) , mean change from baseline in HbA1c was −1.318%; 161/417 (38.6%) achieved HbA1c <7.0%; Mean change from baseline in FPG, 2h-PPG, weight and waist circumference was −1.826 mmol/L, −5.466 mmol/L, −1.89 kg and -2cm, respectively. Conclusion: Dapagliflozin showed a good safety profile in real-world clinical practice in China, with a low incidence of AEs, especially AESI. Meanwhile, a trend of improvement was found in blood glucose control as well as other metabolic factors.
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