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Aim: To compare the efficacy and safety of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs). Methods: In Soli‐D, a 24‐week, multicentre, open‐label, study, insulin‐naïve adults were randomized 1:1 to once‐daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium‐glucose co‐transporter‐2 inhibitors. The primary endpoint was non‐inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed. Results: At week 24, iGlarLixi showed non‐inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: −0.20 [95% confidence interval {CI}: –0.33, −0.07]; P <.001 for non‐inferiority; [97.5% CI: –0.35, −0.05]; P =.003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of −1.49 kg in favour of iGlarLixi (97.5% CI: –2.32, −0.66; P <.001). Event rates (per person‐year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported. Conclusions: In Chinese people with T2D suboptimally controlled with OADs, once‐daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp. [ABSTRACT FROM AUTHOR]

The article discusses the results of a randomized controlled trial comparing the efficacy and safety of two insulin treatments for Chinese people with type 2 diabetes. The study found that insulin glargine 100 U/mL + lixisenatide (iGlar-Lixi) was more effective in reducing postprandial glucose (PPG) levels compared to insulin degludec + insulin aspart (IDegAsp). The timing of the injections was important, with iGlar-Lixi injected before the first meal of the day and IDegAsp injected before the main meal of the day. Overall, both treatments effectively addressed PPG in Chinese people with type 2 diabetes. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin. Materials and Methods: In DUAL II China, a randomized, double‐blinded, multicentre, treat‐to‐target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)‐confirmed hypoglycaemic episodes (confirmatory secondary endpoints). Results: Overall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (−1.9% vs. −1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: −0.92% [−1.09; −0.75], P <.0001), body weight change (−0.7 vs. +0.4 kg, respectively, ETD [95% CI]: −1.08 kg [−1.63; −0.52], P =.0002) and severe or BG‐confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P =.0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P <.0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P =.0014). No unexpected safety signals were observed. Conclusions: IDegLira may be an efficacious and well‐tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have emerged as a promising therapy for type 2 diabetes (T2D). Mechanistic researches demonstrate that the anti-diabetic effect of MSCs is partially mediated by eliciting macrophages into an anti-inflammatory phenotype thus alleviating insulin resistance. However, single MSC infusion is insufficient to ameliorate sustained hyperglycemia or normalize blood glucose levels. In this study, we used decitabine (DAC), which is involved in the regulation of macrophage polarization, to test whether MSCs combined with decitabine can prolong and enhance the anti-diabetic effect in T2D mice. Methods: High-fat diet (HFD) and streptozocin (STZ) were given to induce T2D mouse model. Successfully induced T2D mice were randomly divided into four groups: T2D group, MSC group, DAC group, and MSC + DAC group. Blood glucose was monitored, and glucose tolerance and insulin sensitivity were evaluated during the entire analysis period. Epididymal fat was extracted for analysis of macrophage phenotype and inflammation in adipose tissue. In vitro, we examined the effect of MSC + DAC on macrophage polarization in bone marrow-derived macrophages (BMDMs) and explore the possible mechanism. Results: MSC infusion effectively improved insulin sensitivity and glucose homeostasis in T2D mice within 1 week, whereas combination therapy of MSCs + DAC extended the anti-diabetic effects of MSCs from 1 to 4 weeks (the end of the observation). Correspondingly, more M2 macrophages in adipose tissue were observed in the combination therapy group over the entire study period. In vitro, compared with the MSC group, MSCs combined with decitabine more effectively polarized M1 macrophages to M2 macrophages. Further analysis showed that the effect of MSC + DAC on macrophage polarization was largely abrogated by the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662. Conclusions: Our data suggest that MSCs combined with decitabine can more effectively alleviate insulin resistance and prolong and enhance the anti-diabetic effect of MSCs in T2D mice in part by prompting M2 polarization in a PPARγ-dependent manner. Thus, decitabine may be an applicable addition to MSCs for diabetes therapy. UC-MSCs combined with decitabine activate the IL4R/STAT6/STAT3/PPARγ axis to further promote M2 macrophage polarization in adipose tissue, reduce inflammation, improve insulin sensitivity, and lead to better glucose metabolism and long-term hypoglycemic effects [ABSTRACT FROM AUTHOR]