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In a 13-week, randomized trial involving persons 6 to 79 years of age with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction in the glycated hemoglobin level than standard care.

Combining a glucagon-like peptide-1 receptor agonist (GLP1-RA) with basal insulin is an emerging option when initiating injectable therapy in longstanding type 2 diabetes (T2DM). Recognizing that short-term insulin therapy can improve beta-cell function and induce glycemic remission in early T2DM, we hypothesized that adding the short-acting GLP1-RA exenatide to basal insulin in early T2DM may enhance the achievability of these outcomes. In this completed, 20-week, open-label, parallel-arm trial at an academic hospital, 103 individuals aged 30–80 years with <7 years duration of T2DM were randomized (by computer-generated sequence) to 8-weeks treatment with (i) insulin glargine (Glar; n  = 33), (ii) glargine + thrice-daily lispro (Glar/Lispro; n  = 35), or (iii) glargine + twice-daily exenatide (Glar/Exenatide; n  = 35), followed by 12-weeks washout. The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide. Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control. Mean ISSI-2 over the 8-week intervention (primary outcome) did not differ across the groups (Glar/Exenatide 237 ± 11; Glar/Lispro 208 ± 11; Glar 223 ± 11; p  = 0.19). Baseline-adjusted A1c at 8-weeks (secondary outcome) was lowest in Glar/Exenatide followed by Glar/Lispro and Glar (mean 5.9% vs 6.0% vs 6.2%; p  = 0.0007). After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p  = 0.35). There were no severe hypoglycemia episodes. In conclusion, adding exenatide to basal insulin in early T2DM does not further enhance underlying beta-cell function or the capacity to achieve diabetes remission, despite yielding on-treatment glycemic benefit. Combining a GLP-1 receptor agonist, to increase endogenous beta cell function, with exogenous insulin is a possible therapeutic option for the treatment of type 2 diabetes. Here, the authors show adding exenatide to basal insulin in early type 2 diabetes does not further enhance underlying pancreatic beta-cell function or the capacity to achieve diabetes remission, but may yield on-treatment glycemic benefits.

目的: 探讨5种基础胰岛素治疗在尚未接受胰岛素治疗的2型糖尿病(T2DM)患者的有效性、安全性、最佳起始剂量、最佳维持剂量范围及空腹血糖目标。 方法: 检索2000年1月至2022年2月MEDLINE、EMBASE、Web of Science、Cochrane Library等数据库。遵循系统综述和 meta 分析的首选报告项目(PRISMA)指南并采用建议、评估、发展和评价的分级(GRADE)方法。在PROSPERO的注册ID为CRD42022319078。 结果: 共检索到文献11163篇, 符合纳入标准的文献35篇。从 meta 分析和网络 meta 分析中, 我们发现, 在睡前注射基础胰岛素方案时, 最优选择可能是甘精胰岛素U‐300或德谷胰岛素U‐100、甘精胰岛素U‐100或地特胰岛素, 其次是低精蛋白锌胰岛素(NPH)。与睡前注射相比, 早晨注射甘精胰岛素U‐100可能更有效(即更多患者能够实现HbA 1c <7.0%), 且低血糖事件更少。任何基础胰岛素起始的最佳起始剂量可为0.10‐0.20 U/kg/天。没有合适的证据来研究基础胰岛素的最佳维持剂量。 结论: 5种基础胰岛素对目标人群有效。与NPH相比, 甘精胰岛素U‐300、德谷胰岛素U‐100、甘精胰岛素U‐100和地特胰岛素在不影响血糖控制的情况下可减少低血糖事件。

To the Editor: Rosenstock et al. (July 27 issue) 1 report the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100. Although rates of hypoglycemic events were low in both groups, it is noteworthy that three participants receiving insulin icodec had 105 of the 226 clinically significant hypoglycemic events, whereas no participants receiving insulin glargine U100 had more than 10 clinically significant hypoglycemic events (Table S3 in the Supplementary Appendix, available with the full text of the article at NEJM.org). Such repeated episodes of clinically significant hypoglycemia are surprising, given that the current trial (ONWARDS 1) . . .

We assessed whether comparative efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) plus metformin versus BIAsp 30 monotherapy differed for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetic drugs with different cardiovascular risk scores and different body mass indexes (BMI) by performing a post hoc analysis of the randomized controlled MERIT study. In the MERIT study, eligible patients were randomized 1:1 to receive BIAsp 30 plus metformin or BIAsp 30 for 16 weeks. Patients in the 2 treatment groups were classified into “low” and “high” risk subgroups based on their GloboRisk scores and into “BMI ≤ 26 kg/m 2 ”and “BMI > 26 kg/m 2 ” subgroups. Primary efficacy endpoint was between-treatments comparison of HbA1c changes from baseline for these 2 sets of subgroups. Between-treatments comparisons of secondary efficacy and safety endpoints were also performed. We found that BIAsp 30 plus metformin led to significantly higher percentage of high-risk patients achieving HbA1c target < 7% than BIAsp 30 monotherapy, with an overall comparable safety profile for high-risk patients. Meanwhile, for patients with BMI ≤ 26 kg/m 2 , compared with BIAsp 30 monotherapy, BIAsp 30 plus metformin led to significantly higher percentages of patients achieving HbA1c target (47.83% vs 28.17%, P  = 0.0165) and composite target of HbA1c < 7% without hypoglycemia or weight gain (20.29% vs 6.85%, P  = 0.0187) and have a slightly better safety profile. In conclusion, for T2DM patients at high CV risk or with BMI ≤ 26 kg/m 2 , BIAsp 30 plus metformin was preferable to BIAsp 30 monotherapy.

Aims/Introduction We compared the efficacy and safety of insulin degludec/aspart (IDegAsp) twice‐daily injections with insulin glargine 300 U/mL and insulin glulisine basal–bolus therapy (Gla300/Glu) using insulin glargine 300 U/mL (Gla300) and insulin glulisine (Glu). Materials and Methods A total of 20 patients with type 2 diabetes mellitus were treated with IDegAsp twice‐daily injections; achievement of target preprandial glucose concentration of 100–130 mg/dL at breakfast and supper was determined using a wearable flash glucose monitoring system. Patients were later switched to Gla300/Glu basal–bolus therapy before breakfast and before supper. Data were collected on days 2–4 and days 12–14 for each treatment period. The study's primary efficacy end‐point was the mean percentage of time with a target glucose range of 70–180 mg/dL, and safety end‐points were the mean percentage of time with hypoglycemia having glucose levels <70 mg/dL, clinically important hypoglycemia with glucose levels <54 mg/dL and nocturnal (00.00–06.00) hypoglycemia. Results Considering efficacy, the mean percentage of time for the target glucose range of IDegAsp was significantly lower than that of Gla300/Glu (73.1 [69.4–81.1] vs 84.2 [80.2–93.1], P = 0.001). Considering safety, the mean percentages of hypoglycemia (<70 mg/dL; 2.1 [0.0–9.4] vs 14.4 [4.4–22.3]), clinically important hypoglycemia (<54 mg/dL; 0.0 [0.0–0.2] vs 1.9 [0.0–5.6]) and nocturnal (00.00–06.00 hours) hypoglycemia (0.5 [0.0–5.9] vs 8.9 [3.1–11.8]) of Gla300/Glu were significantly lower than those of IDegAsp (P = 0.012, 0.036 and 0.007, respectively). Conclusions When compared with the IDegAsp twice‐daily injections, Gla300/Glu basal–bolus therapy might achieve more effective glycemic control without hypoglycemic risk. When compared with insulin degludec/aspart twice‐daily injections, insulin glargine 300 U/mL and insulin glulisine basal–bolus therapy might achieve more effective glycemic control without hypoglycemic risk.

Objective. To observe whether there are sexual-related differences in response to mid- or low-premixed insulin in type 2 diabetic patients. Methods. This was an analysis of CGM data of a previous study. After screening, patients with longstanding T2D receive a 7-day continuous subcutaneous insulin infusion (CSII) therapy, and then subjects were randomly assigned 1 : 1 into two groups receiving Novo Mix 30 or Humalog Mix 50 regimen for a 2-day phage, followed by a 4-day cross-over period. A 4-day continuous glucose monitoring (CGM) was performed during the cross-over period. The primary endpoint was the differences in glycemic control between male and female patients receiving mid- or low-premixed insulin therapy. Results. A total of 102 patients (52 men and 50 women) completed the study. Our data showed that male patients had significant decrease in mean glucose levels monitored by CGM after three meals during Humalog Mix 50 treatment period compared to those received Novo Mix 30 regimen (0900: 11.0±2.5 vs. 12.2±2.8, 1000: 9.9±2.9 vs. 11.3±3.1, 1200: 8.0±1.9 vs. 9.1±2.5, 1400: 9.2±2.3 vs. 10.3±2.5, and 2000: 7.3±2.1 vs. 8.2±2.4 mmol/L, p<0.05, respectively). In addition, male patients receiving Novo Mix 30 experienced a significantly increased hypoglycemic duration compared to those of receiving Humalog Mix 50 (0 (0, 4.8) vs. 0 (0, 0), p<0.05). Conclusion. Our data indicate that male patients with T2D receiving mid-premixed insulin analogue regimen may have a potential benefit of improvement in glycemic control compared to female patients. This trial is registered with ClinicalTrials.gov ChiCTR-IPR-15007340.

To compare the response to different insulin regimens for management of hyperglycemia in diabetic patients with hematologic malignancies who are receiving dexamethasone. A retrospective analysis was conducted to determine whether a basal bolus insulin (BBI) regimen with detemir and aspart is superior to a sliding scale regular insulin (SSI) regimen for management of hyperglycemia in hospitalized diabetic patients receiving dexamethasone. Forty patients with hematologic malignancies were treated with intravenous (8 to 12 mg/day) or oral (40 mg/day) dexamethasone for 3 days. The average blood glucose (BG) level was 301 ± 57 mg/dL in the SSI group (n = 28) and 219 ± 51 mg/dL in the BBI group (n = 12) (P <.001). The BBI regimen resulted in an average BG reduction of 52 ± 82 mg/dL throughout the course of dexamethasone therapy, while the SSI regimen produced an increase in the mean daily BG level of 128 ± 77 mg/dL (P <.001). On the last day of dexamethasone administration, the insulin requirement was 49 ± 29 units/day in the SSI group and 122 ± 39 units/day in the BBI group (P <.001). Three patients in the SSI group developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy. No hypoglycemia was observed in either group. The length of stay and infection rates were similar between groups. Basal and bolus insulin regimen is an effective and safe approach for managing dexamethasone-induced hyperglycemia in hospitalized patients with hematologic malignancies.

To evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL). This 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A(1c) [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning. At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (-0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: -0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001). In patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.

OBJECTIVE: To examine the effect of intensive glycemic control therapy (IT) on insulin sensitivity and β-cell function in newly diagnosed type 2 diabetic patients compared with subjects with normal glucose tolerance (NGT) and those with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Forty-eight newly diagnosed type 2 diabetic patients were randomly assigned to IT for 2 weeks and followed up for 1 year. Intravenous glucose tolerance tests were conducted in NGT, IGT, and diabetic subjects. Blood glucose and insulin were measured before and after IT and at the 1-year follow-up. RESULTS: IT lowered the homeostasis model assessment (HOMA) for insulin resistance (IR) significantly, from 3.12 ± 1.4 (mean ± SD) to 1.72 ± 0.8, a level comparable to the IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) subjects in the remission group; however, no HOMA-IR improvement was observed in nonremission subjects. HOMA-β in the remission group was improved (mean, interquartile range) from 18.4 (8.3-28.5) to 44.6 (32.1-69.1) and acute insulin response of insulin (AIRins) from 1.50 ± 0.22 to 1.83 ± 0.19 μIU/mL after IT, but was still significantly lower than those in NGT individuals (HOMA-β: 86.4 [56.7-185.2], P < 0.01; AIRins: 2.54 ± 0.39 μIU/mL, P < 0.01). After IT and at 1 year, the hyperbolic relationship between HOMA-β and HOMA sensitivity of remission subjects shifted close to that of IGT subjects. CONCLUSIONS: IT in newly diagnosed type 2 diabetes not only partially restored β-cell function but also greatly restored insulin sensitivity. Compared with IGT and NGT subjects, β-cell function was less restored than insulin sensitivity after IT in the remission subjects.