Efficacy of metformin in preventing progression to diabetes in a Chinese population with impaired glucose regulation: Protocol for a multicentre, open-label, randomized controlled clinical study.

AIM: To investigate the effectiveness of metformin in delaying or preventing progression to diabetes in a Chinese population with impaired glucose regulation (IGR). MATERIALS AND METHODS: This multicentre, randomized, open-label, controlled study (NCT03441750) will assess the efficacy of metformin in preventing diabetes over ≥2 years. Eligible participants will be randomly assigned (1:1) to lifestyle intervention (LSI) or metformin plus LSI, with stratification based on blood pressure, anti-hypertensive medication use and isolated/non-isolated impaired fasting glucose. All participants will receive LSI advice. Participants in the metformin plus LSI group will receive metformin 850 mg once daily for the first 2 weeks, and twice daily thereafter, according to tolerability. RESULTS: The primary objective is to compare rates of newly diagnosed diabetes in the two intervention groups. Changes in glycaemia, blood pressure, body weight, insulin resistance, and safety outcomes will also be evaluated. CONCLUSIONS: This large clinical trial in a Chinese population with IGR aims to provide critical information to guide clinical decision-making in order to alleviate the current diabetes epidemic.

Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Impaired glucose regulation (defined as either impaired glucose tolerance or impaired fasting glucose) is an important risk factor for the development of diabetes. We aimed to evaluate the safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing diabetes in Chinese participants with impaired glucose regulation. METHODS: We did a multicentre, open-label, randomised controlled trial at 43 endocrinology departments in general hospitals across China. Eligible participants were individuals with impaired glucose regulation (ie, impaired glucose tolerance or impaired fasting glucose, or both), men or women aged 18-70 years with a BMI of 21-32 kg/m2. Eligible participants were randomly assigned (1:1) via a computer-generated randomisation to receive either standard lifestyle intervention alone or metformin (850 mg orally once per day for the first 2 weeks and titrated to 1700 mg orally per day [850 mg twice per day]) plus lifestyle intervention. Block randomisation was used with a block size of four, stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), hypertension, and use of any anti-hypertensive medication. Lifestyle intervention advice was given by investigators at all participating sites. The primary endpoint was the incidence of newly diagnosed diabetes at the end of the 2-year follow-up. Analysis was done using the full analysis set and per-protocol set. This study is registered with ClinicalTrials.gov, number NCT03441750, and is completed. FINDINGS: Between April, 2017, and June, 2019, 3881 individuals were assessed for eligibility, of which 1678 (43·2%) participants were randomly assigned to either the metformin plus lifestyle intervention group (n=831) or the lifestyle intervention alone group (n=847) and received the allocated intervention at least once. During a median follow-up of 2·03 years, the incidence rate of diabetes was 17·27 (95% CI 15·19-19·56) per 100 person-years in the metformin plus lifestyle intervention group and 19·83 (17·67-22·18) per 100 person-years in the lifestyle intervention alone group. The metformin plus lifestyle intervention group showed a 17% lower risk of developing diabetes than the lifestyle intervention alone group (HR 0·83 [95% CI 0·70-0·99]; log-rank p=0·043). A higher proportion of participants in the metformin plus lifestyle intervention group reported adverse events than in the lifestyle intervention alone group, primarily due to more gastrointestinal adverse events. The percentage of participants reporting a serious adverse event was similar in both groups. INTERPRETATION: Metformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. FUNDING: Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial.

OBJECTIVE: This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin. METHODS: This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c <7.0% and ≤6.5%. RESULTS: 590 patients with type 2 diabetes mellitus were randomized to Rapilin (n = 441) and NovoRapid (n = 149) groups. After 24 weeks, the mean HbA1c change from baseline was -2.20% (Rapilin) and -2.32% (NovoRapid); the estimated treatment difference based on least-square means was 0.04% (95% CI: -0.17, 0.26), meeting the noninferiority criteria for Rapilin versus NovoRapid. Comparable improvements were reported for mean 2-hour PPG (6.14 and 6.29 mmol/L), FPG (2.02 and 1.70 mmol/L), and patients with HbA1c <7.0% (52.6% and 51.0%) and ≤6.5% (34.2% and 30.9%), in the Rapilin and NovoRapid groups, respectively, with no significant safety or immunogenicity outcome differences. CONCLUSIONS: Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks. TRIAL REGISTRATION: ChiCTR20003129041.

Carbon dioxide sequestration and methane production promotion by wollastonite in sludge anaerobic digestion.

This study investigated the feasibility and performance of simultaneous in-situ CO2 sequestration and CH4 production promotion by wollastonite addition in sludge AD. A maximum CH4 yield increment of 30.8% and maximum methane production rate increment of 64.9% with wollastonite addition at dosage of 16.25 g/L were achieved. CO2 was efficient sequestered by wollastonite addition and resulted in a higher CH4 content of 81.7%-82.4%. The mechanism of CO2 sequestration by wollastonite was confirmed as Ca2+ release and subsequently carbonation based on cation and precipitates analysis. The results demonstrated that wollastonite could be applied as an effective additive for simultaneous in-situ CO2 sequestration and CH4 production promotion of sludge AD.

[The protection effect of a new combined anti-G measure].

AIM: To observe the protection effect of a new combined anti-G measure which was composed of KH-x anti-G suit, unassisted PBG (positive pressure breathing for G, PBG) and PHP maneuver. The problem of fatigue and pain when using this measure was also discussed. METHODS: Five fully qualified centrifuge subjects were exposed to 5 groups of +Gz exposure: (1) relaxed tolerance, (2) KH-x and KT-x, (3) PBG, (4) 6.5 G 45 s, (5) 9.0 G 15 s. The subjective feeling of fatigue and pain induced by +Gz exposure was evaluated by the questionnaire after runs. RESULTS: There was no incidents of G-induced lose of consciousness in this study. The protective effect of KH-x and KT-x was 2.3 G while it was 1.7 G for PBG. All the subjects have accomplished the 4th and 5th runs. The pain has developed on neck, waist, arm and hands. The problem of waist pain was very significant. CONCLUSION: The new combined anti-G measure could meet the requirement of +9.0 Gz protection for high performance plane. How to prevent the occurrence of neck injury and alleviate the pain induced by G when using this measure should be studied further.