Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Efficacy and safety of a basal insulin + 2-3 oral antihyperglycaemic drugs regimen versus a twice-daily premixed insulin + metformin regimen after short-term intensive insulin therapy in individuals with type 2 diabetes: The multicentre, open-label, randomized controlled BEYOND-V trial.

AIM: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China. MATERIALS AND METHODS: This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). RESULTS: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group. CONCLUSIONS: Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V).

INTRODUCTION: Many Chinese patients who are uncontrolled by oral antidiabetic drugs (OADs) receive short-term intensive insulin therapy (IIT) in hospital to rapidly relieve glucose-associated toxicity and to preserve/improve ß-cell function. However, evidence for optimizing insulin algorithms for maintenance treatment after IIT is lacking. This study will compare the efficacy and safety of basal insulin-based treatment versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term in-hospital IIT. METHODS: This 26-week randomized, multicenter, positive-controlled, open-label, parallel-group study will enroll approximately 400 male and female patients aged 18-70 years with poorly-controlled T2DM (HbA1c > 7.5%) despite treatment with metformin plus at least one other OAD for 8 or more weeks. During a run-in period of 7-10 days, patients will be treated in-hospital with IIT comprising insulin glargine (Lantus®) once daily and insulin glulisine (Apidra®) three times daily; both regimens will be titrated daily to achieve the glycemic goal. Eligible patients will then be randomized in a 1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin (NovoLog® Mix 70/30) for 24 weeks, with metformin maintained throughout the study in both treatment groups. The primary endpoint is HbA1c change from baseline to week 24. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction. DISCUSSION: Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT. This will assist physicians by providing a wider choice of treatments. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03359837 (registered on 2 December 2017).

Passive sampling of polybrominated diphenyl ethers in indoor and outdoor air in Shanghai, China: seasonal variations, sources, and inhalation exposure.

Ninety-seven seasonal, passive indoor and outdoor air samples were collected in Shanghai to study polybrominated diphenyl ethers (ΣPBDEs, 16 congeners including BDE-209), their concentrations, composition profiles, seasonal variations, influencing factors, emission sources, and human inhalation exposure. In summer, median indoor concentrations of Σ 15 PBDEs (excluding BDE-209) were 82 pg m(-3) in offices and 30 pg m(-3) in homes, ∼3 times the winter concentrations. The average summer concentration of 130 pg m(-3) BDE-209 in homes was higher than that in offices (which was 90 pg m(-3)); in winter, home and office concentrations were similar (46 and 47 pg m(-3), respectively). For outdoor air, the median concentration of Σ 15 PBDEs in summer (12 pg m(-3)) was twice the winter concentration (6 pg m(-3)), while the summer median concentration of BDE-209 (398 pg m(-3)) was half the winter concentration (794 pg m(-3)). Higher concentrations of Σ 15 PBDEs indoors compared with outdoors showed that the lower brominated BDEs found were mainly from indoor sources. Meanwhile, the much lower indoor concentration of BDE-209 compared with the outdoors showed that BDE-209 came mainly from outdoor sources. The data set also indicated that electric/electronic appliances were the main sources of indoor ΣPBDEs, and old appliances emitted more lower brominated BDEs, while industrial emissions should be the main source of the outdoor BDE-209. Median daily human exposures to Σ 15 PBDEs and BDE-209 through inhalation were estimated to be 0.23 and 1.73 ng day(-1) in winter and 0.65 and 2.28 ng day(-1) in summer for adults. The human inhalation exposure to ΣPBDEs (3.44 ng day(-1) for adults and 1.33 ng day(-1) for toddlers) was comparable to that from eating contaminated fish for both toddlers and adults in Shanghai.