More patients reach glycaemic control with a fixed‐ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time‐to‐control analysis of LixiLan‐O and LixiLan‐L

The present post hoc analysis of two 30‐week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan‐O trial) or basal insulin (LixiLan‐L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan–Meier method. In the LixiLan‐O and LixiLan‐L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan‐O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan‐L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time‐to‐target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.     

iGlarLixi effectively reduces residual hyperglycaemia in patients with type 2 diabetes on basal insulin: A post hoc analysis from the LixiLan-L study

Globally, nearly half of patients with type 2 diabetes (T2D) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycaemia in patients with T2D. In LixiLan-L, a randomized, open-label study, 1018 patients with T2D on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Following the run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycaemia was defined as HbA1c ≥ 7.0% despite FPG of <140 mg/dL. The proportion of patients with residual hyperglycaemia was similar in both treatment arms at screening (~~42%), and increased after the run-in period (~~62%). After 30 weeks, the proportion of patients with residual hyperglycaemia declined to 23.8% in the iGlarLixi versus 47.1% in the iGlar arm (P < .0001). The proportion of patients achieving both HbA1c (<7.0%) and FPG (<140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively; P < .0001). iGlarLixi effectively reduces residual hyperglycaemia in patients with T2D on basal insulin therapy.     

Impact of baseline glycated haemoglobin,diabetes duration and body mass index on clinical outcomes in the LixiLan‐O trial testing a titratable fixed‐ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and lixisenatide monocomponents

To determine whether baseline characteristics had an impact on clinical outcomes in the LixiLan‐O trial (N = 1170), we compared the efficacy and safety of iGlarLixi, a titratable fixed‐ratio combination of insulin glargine 100 U (iGlar) and lixisenatide (Lixi) with iGlar or Lixi alone in patients with uncontrolled type 2 diabetes mellitus (T2DM) on oral therapy. Subgroups according to baseline glycated haemoglobin (HbA1c; <8% or ≥8% [<64 or ≥64 mmol/mol]), T2DM disease duration (<7 or ≥7 years) and body mass index (BMI; <30 or ≥30 kg/m²) were investigated. In all subpopulations, iGlarLixi was consistently statistically superior to iGlar and Lixi alone in reducing HbA1c from baseline to week 30; higher proportions of patients achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi vs iGlar and Lixi alone. Compared with iGlar, iGlarLixi resulted in a substantial decrease in 2‐hour postprandial plasma glucose levels, and mitigation of weight gain, with no differences among subpopulations in incidence of symptomatic hypoglycaemia. iGlarLixi consistently improved glycaemic control compared with iGlar and Lixi alone, without weight gain or increase in hypoglycaemic risk compared with iGlar in the subpopulations tested, regardless of baseline HbA1c, disease duration and BMI.     

Insulin glargine/lixisenatide fixed-ratio combination improves glycaemic variability and control without increasing hypoglycaemia

Maintaining optimal glycaemic control reduces the risk of micro- and macrovascular complications in patients with type 2 diabetes. Typically, glycaemic control is based on glycated haemoglobin (HbA1c) as a measure of mean glucose concentration; however, this marker does not accurately reflect glycaemic variability (GV), which is characterized by the amplitude, frequency and duration of hypo- and hyperglycaemic fluctuations. In the present study, we analysed data from the LixiLan-O trial, which compared iGlarLixi, a titratable fixed-ratio combination of the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi) and long-acting basal insulin glargine 100 units/mL (iGlar), with its individual components, and the LixiLan-L trial, which compared iGlarLixi with iGlar. The GV features that were measured were mean and SD of self-measured plasma glucose (SMPG), high blood glucose index (HBGI) and low blood glucose index, area under the SMPG curve for each patient (AUCn), mean absolute glucose (MAG) and mean amplitude of glycaemic excursions (MAGE). By week 30, iGlarLixi improved all GV markers from baseline, with no increased hypoglycaemia risk. Significant improvements were observed in SMPG, SD of SMPG, HBGI, AUCn, MAG and MAGE compared with iGlar, and in SMPG, HBGI and AUCn, compared with Lixi.     

iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis

Aim

To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose.

Methods

Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated.

Results

The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD₁: 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD₂: 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi.

Conclusion

iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.     

Mexican population sub-analysis of the lixilan clinical program with the fixed ratio combination of insulin glargine and lixisenatide (iGlarLixi)

AimTo evaluate the efficacy and safety of iGlarLixi in Mexican patients with type 2 diabetes who participated in the LixiLan clinical trials and compare results with the rest of the patients.MethodsData was collected for Mexican patients who participated in either of three studies: phase 2 trial LixiLan-POC, that compared iGlarLixi vs insulin glargine (iGlar) on inadequately controlled patients with metformin; phase 3 trial LixiLan-O, comparing iGlarLixi vs iGlar and lixisenatide on inadequately controlled patients with oral antidiabetic agents; and finally the phase 3 trial LixiLan-L, comparing iGlarLixi vs iGlar on inadequately controlled patients with basal insulin. The primary endpoint was the change in HbA1c from baseline to end of treatment.ResultsIn the Mexican population, treatment with iGlarLixi significantly improved HbA1c compared with each component alone achieving an average of 6.5%; (6.17%, 6.63% and 6.73% for the LixiLan-POC, O and L studies respectively) and an average HbA1c reduction from baseline of 1.6%, for the three studies at end of treatment period.ConclusionThe efficacy and safety profile of iGlarLixi demonstrate a fair or better composite endpoint of HbA1c without hypoglycemia and no weight gain compared to overall trial population, which could help improve Mexican patients' outcomes.     

The Differential and Combined Action of Insulin Glargine and Lixisenatide on the Fasting and Postprandial Components of Glucose Control

Background:iGlarLixi is an injectable combination of long acting insulin glargine (iGlar) and glucagon-like peptide 1 receptor agonist lixisenatide in a fixed ratio, which was proven safe and effective for the treatment of type 2 diabetes. Lixisenatide and iGlar act differently on fasting and postprandial plasma glucose (fasting plasma glucose [FPG] and postprandial glucose [PPG]). Here, we deconstruct quantitatively their respective FPG and PPG effects.Method:This post hoc study analyzes data from the Lixilan-O trial, where 1170 subjects with type 2 diabetes were randomly assigned to 30 weeks of once daily injections of lixisenatide, iGlar, and iGlarLixi (1:2:2). The FPG and PPG components of glucose control were assessed in terms of mean glucose (fasting mean plasma glucose [FMPG] and prandial mean plasma glucose [PMPG], respectively). The MPGP was computed across all meals as a delta between post- and premeal glucose; glucose variability was measured by the high blood glucose index (HBGI) (fasting HBGI and prandial HBGI [PHBGI], respectively), and glycemic exposure measured by area under the curve (AUC) computed overall. All metrics were derived from seven-point self-monitoring glucose profiles.Results:Insulin glargine lowered significantly FMPG by 15.3 mg/dL (P < .01) without any significant change in PMPG. Lixisenatide, when added to iGlar, reduced PMPG by 9.7 mg/dL (P < .01), AUC by 96.3 mg∙h/dL (P < .01), and PHBGI by 2.4 (P < .01), primarily due to attenuation of PPG and without significant change in mean FPG.Conclusion:Insulin glargine and lixisenatide act selectively on FPG and PPG. Their combination iGlarLixi offers more effective glucose control than its components due to the cumulative effect on FPG and PPG, which is evidenced by reduced average glycemia, glycemic exposure, and glucose variability.     

Fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge

Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation because of the progressive nature of T2D, this appears to be suboptimal in Japanese real-world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean glycated haemoglobin >9%). Although basal insulin therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose often remains uncontrolled. Basal-bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed-ratio combinations (FRCs) of BI and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing both FPG and postprandial plasma glucose with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide, is currently available in Japan and the United States/European Union at a ratio of 1 U (unit):0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 1:1 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D.     

Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.     

Efficacy and safety of insulin glargine/lixisenatide (iGlarLixi) fixed-ratio combination in older adults with type 2 diabetes

Aims

This study assessed the efficacy and safety of iGlarLixi (a titratable, fixed-ratio combination of insulin glargine [iGlar] plus lixisenatide) in older patients with type 2 diabetes.

iGlarLixi (insulin glargine 100 U/ml plus lixisenatide) is effective and well tolerated in people with uncontrolled type 2 diabetes regardless of age: A REALI pooled analysis of prospective real-world data

Aim

To evaluate the effectiveness and safety in routine clinical practice of insulin glargine/lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) according to age.

Methods

Patient-level data were pooled from 1316 adults with T2D inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi for 24 weeks. Participants were classified into age subgroups of younger than 65 years (N = 806) and 65 years or older (N = 510).

Results

Compared with participants aged younger than 65 years, those aged 65 years or older had a numerically lower mean body mass index (31.6 vs. 32.6 kg/m²), a longer median diabetes duration (11.0 vs. 8.0 years), were more likely to receive prior basal insulin (48.4% vs. 43.5%) and had a lower mean HbA1c (8.93% [74.10 mmol/mol] vs. 9.22% [77.28 mmol/mol]). Similar and clinically relevant reductions in HbA1c and fasting plasma glucose from baseline to week 24 of iGlarLixi therapy were observed regardless of age. At 24 weeks, least-squares adjusted mean (95% confidence interval [CI]) change in HbA1c from baseline was –1.55% (–1.65% to –1.44%) in those aged 65 years or older and –1.42% (–1.50% to –1.33%) in those aged younger than 65 years (95% CI: –0.26% to 0.00%; P = .058 between subgroups). Low incidences of gastrointestinal adverse events and hypoglycaemic episodes were reported in both age subgroups. iGlarLixi decreased mean body weight from baseline to week 24 in both subgroups (–1.6 kg in those aged ≥ 65 years and –2.0 kg in those aged < 65 years).

Conclusions

iGlarLixi is effective and well tolerated in both younger and older people with uncontrolled T2D.     

Advancing therapy in people with suboptimally controlled basal insulin-treated type 2 diabetes: Subanalysis of the SoliMix trial in participants in Latin American countries

Aims

This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160).

Materials and Methods

SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30.

Results

Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference −0.47% (95% confidence interval: −0.82, −0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference −1.27% (95% confidence interval: −2.41, −0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30.

Conclusions

Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region.     

The role of new basal insulin analogues in the initiation and optimisation of insulin therapy in type 2 diabetes

Intensive insulin therapy aimed at achieving normoglycaemia is becoming increasingly accepted in the treatment of type 2 diabetes (T2DM) to reduce the risk of diabetes-related complications. Insulin therapy is increasingly combined with oral antidiabetic drugs (OADs) to moderate insulin dosage, reduce weight gain and confer cardiovascular protection. However, traditional insulins are associated with limitations that may act as barriers to initiation, and intensive use of insulin therapy. The advent of newer, longer-acting, basal insulin analogues, such as insulin glargine (glargine) and insulin detemir (detemir), offer improved pharmacokinetic and pharmacodynamic profiles compared with neutral protamine Hagedorn insulin (NPH). This potentially provides concomitant improvements in safety, efficacy and variability of glycaemic control. This paper reviews the properties of these new long-acting, basal insulin analogues and their potential roles in facilitating the initiation and optimisation of insulin therapy. Studies that reported the use of insulin and insulin analogues for the treatment of T2DM were identified using Medline. Key search terms included: ‘insulin glargine’, ‘insulin detemir’, ‘NPH insulin’, ‘basal insulin’, ‘long-acting insulin’, ‘insulin analogue’, ‘pharmacokinetics’, ‘pharmacodynamics’, ‘dose titration’, ‘algorithms’ and ‘type 2 diabetes’. Abstracts presented at the American Diabetes Association and the European Association for the Study of Diabetes annual congresses were also searched. The data show that the long-acting insulin analogues glargine and detemir both offer a low risk of hypoglycaemia and improved glycaemic control. Aggressive dose titration with glargine and detemir facilitates attainment of glycaemic control targets. The goal of achieving good glycaemic control with a low risk of hypoglycaemia may be more feasible with newer insulin therapies as part of a simple basal insulin regimen with continued OADs.     

Insulin degludec/liraglutide (IDegLira) was effective across a range of dysglycaemia and body mass index categories in the DUAL V randomized trial

This study assessed the efficacy of insulin degludec/liraglutide (IDegLira) vs insulin glargine U100 (IGlar) across categories of baseline glycated haemoglobin (HbA1c; ≤7.5%, >7.5% to ≤8.5% and >8.5%), body mass index (BMI; <30, ≥30 to <35 and ≥35 kg/m²) and fasting plasma glucose (FPG; <7.2 and ≥7.2 mmol/L) in patients with type 2 diabetes (T2D) uncontrolled on basal insulin, using post hoc analyses of the DUAL V 26‐week trial. With IDegLira, mean HbA1c was reduced across all baseline HbA1c (1.0%‐2.5%), FPG (1.5%‐1.9%) and BMI categories (1.8%‐1.9%), with significantly greater reductions compared with IGlar U100. For all HbA1c, FPG and BMI categories, IDegLira resulted in weight loss and IGlar U100 in weight gain; hypoglycaemia rates were lower for IDegLira vs IGlar U100. More patients achieved HbA1c <7% with IDegLira than IGlar U100 across all HbA1c (59%‐87% vs 31%‐66%), FPG (71%‐74% vs 40%‐51%) and BMI categories (71%‐73% vs 40%‐54%). IDegLira improved glycaemic control and induced weight loss in patients with T2D previously uncontrolled on basal insulin, across the categories of baseline HbA1c, FPG or BMI that were tested.     

Moderate guar-gum addition to usual diet improves peripheral sensitivity to insulin and lipaemic profile in NIDDM

The addition of vegetable fibres to the diabetic diet has been reported to ameliorate glycaemic and plasma lipid profiles, and Guar flour seems to obtain the best results. At its usual dose, Guar produces several gastro-intestinal side effects. A lower dose (4 + 4 g/day) was therefore employed in 10 non-insulin dependent diabetics (NIDD). The following parameters were measured at the end of treatment and after a control period: HbA1 levels, hepatic glucose production (3H-Glucose infusion), peripheral sensitivity to insulin and insulin secretion (hyperglycaemic clamp), and specific insulin binding to isolated monocytes. The ultracentrifugal plasma lipid pattern was also measured. No significant body weight change was recorded during the study. A significant glycaemic and insulinaemic decrease in the fasting state was observed after Guar, together with a significant decrease of HbA1 levels (from 8.5 +/- 0.4 to 7.9 +/- 0.4%, p less than 0.05) and amelioration of peripheral sensitivity to insulin (M/I = 14.3 +/- 6.6 versus 24.3 +/- 8.8, p less than 0.025; 50% increase of insulin binding to circulating monocytes) without significant variation of the fasting hepatic glucose production. Decreased B-cell stimulation by flattening post-prandial glycaemic peaks may be an explanation of the reduction of insulin resistance via down-regulation mechanism. As far as the lipid profile is concerned, a significant reduction in total and LDL cholesterol (p less than 0.05 and p less than 0.01) and an increase in HDL-phospholipids (p less than 0.05) were recorded after Guar. These results suggest that Guar in low doses is well accepted and can contribute to a better glycaemic and lipaemic control in NIDDM.     

2009年中国成人2型糖尿病患者口服降糖药联合胰岛素治疗后血糖达标状况调查

目的了解我国2型糖尿病（T2DM）治疗及达标现状,重点了解口服降糖药联合胰岛素治疗血糖达标状况。方法由中华医学会糖尿病学分会“糖化血红蛋白监测网”项目组于2009年7至9月在全国范围内选择具有代表性的75个城市的400家医院参加本横断面研究。正在接受口服降糖药联合／不联合胰岛素治疗的年龄≥18岁的2型糖尿病患者均可进入研究。采用问卷形式调查患者一般信息、糖尿病病程、糖尿病并发症及合并症、糖化血红蛋白（HbAlc）、空腹血糖、餐后血糖及治疗药物。所有数据均使用SAS9．13软件进行统计学处理。结果最终共纳入T2DM患者143123例,其中男73544例,女69579例,中位年龄59岁,中位病程6年。在应用口服降糖药联合胰岛素治疗的患者中,最多应用的是预混胰岛素（65．5％,34487／52649）,其次是基础胰岛素（24．3％,12794／52649）,8．5％（4492／52649）的患者应用基础＋餐时胰岛素。按照HbAlc〈6．5％计算达标率,总体人群达标率为20．2％（28985／143123）。单纯使用口服药治疗的患者HbAlc达标率（23．4％,21163／90474）高于总体人群,使用口服降糖药联合胰岛素的患者HbAlc达标率（14．9％,7822／52649）低于总体人群。不同胰岛素治疗方案组达标率接近[基础胰岛素组15．2％（1944／12794）,预混胰岛素组14．9％（5150／34487）,基础＋餐时胰岛素组14．6％（656／4492）]。随着糖尿病病程延长,各胰岛素治疗方案组达标率均呈降低趋势（均P〈0．05）,早启用胰岛素的患者较晚启用胰岛素的患者达标率更高（均P〈0．01）。T2DM患者血压及血脂达标率分别为：血压23．5％（33676／143123）,甘油三酯37．4％（53550／143123）,总胆固醇41．4％（59320／143123）,高密度脂蛋白胆固醇19．2％（27418／143123）,低密度脂蛋白胆固醇41．7％（59671／143123）。结论我国T2DM患者HbAlc总体达标率低,口服药联合胰岛素的患者达标率低于总体达标率。提示大部分患者仍需要得到更加积极有效的个体化治疗。     

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics

Aim

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics.

Methods

SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function.

Results

No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events.

Conclusions

Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.     

Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies

Aim

To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D).

Materials and Methods

Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52.

Results

The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide.

Conclusions

Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.     

iGlarLixi versus premixed insulin initiation in adults with type 2 diabetes advancing from basal insulin therapy: The SoliComplex real-world study

Aim

To compare outcomes in adults with type 2 diabetes (T2D) suboptimally controlled with basal insulin who initiated treatment with iGlarLixi or premixed insulin.

Methods

This retrospective real-world analysis was conducted using data from adults (age ≥ 18 years) with T2D in the US Optum Clinformatics database who had previously received basal insulin and newly initiated iGlarLixi or premixed insulin. Cohorts were propensity-score matched on baseline characteristics using a greedy nearest neighbour-matching algorithm, and outcomes were assessed at 12 months. Subgroup analyses were performed for those aged 65 years or older and those with a baseline HbA1c of 9% or higher. The primary endpoint was treatment persistence in the overall population. Secondary endpoints were treatment adherence, healthcare resource utilization (HRU), costs, hypoglycaemia events and change in HbA1c from baseline.

Results

Each cohort comprised 834 participants. In the overall population, treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus premixed insulin: 42.5% versus 39.1%; hazard ratio 0.88; 95% confidence interval 0.778-0.998; P = .0465. Adherence and HbA1c reduction were similar between groups, whereas hypoglycaemia events, HRU and costs were numerically lower for iGlarLixi. Outcomes in both the age 65 years or older subgroup and in those with an HbA1c of 9% or higher were consistent with those for the overall population.

Conclusions

In this observational study in people with T2D suboptimally controlled on basal insulin, once-daily iGlarLixi was an effective treatment alternative to premixed insulin with significantly higher treatment persistence, similar adherence and HbA1c reduction, and numerically lower hypoglycaemia events, HRU and costs, regardless of age or baseline HbA1c.     

Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study)

AIM: This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self-titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA(1c)< or =6.5 and <7%). METHODS: Enrolled patients (n = 100, HbA(1c)> or =7.5 and < or =10%) were > or =18 years of age, had diabetes > or =12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once-daily basal insulin < or =60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70-100% of prior basal insulin dose within 15 min of dinner initiation). Patients self-titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre-breakfast fasting blood glucose (FBG) of 80-110 mg/dl. At 16 weeks, a pre-breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA(1c) exceeded 6.5%; the added dose was titrated to achieve pre-dinner BG of 80-110 mg/dl. After an additional 16 weeks, 3 U of pre-lunch BIAsp 30 was added if HbA(1c) exceeded 6.5%. This added dose was adjusted based on 2-h post-lunch BG to achieve postprandial glucose of 100-140 mg/dl. Subjects achieving an HbA(1c)< or =6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively. RESULTS: Addition of once-daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA(1c)< or =6.5%) and 41% to achieve ADA targets (HbA(1c) <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA(1c)< or =6.5%, and 77% achieved HbA(1c) <7.0%. CONCLUSIONS: This clinical trial demonstrates that initiation of once-daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.