Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial

Aim: The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin + metformin vs. saxagliptin or metformin monotherapy in treatment‐naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control. Methods: In this multicentre, randomized, double‐blind, active‐controlled phase 3 trial, 1306 treatment‐naïve patients with T2D ≥18 to ≤77 years, glycosylated haemoglobin (HbA1c) ≥8 to ≤12%, fasting C‐peptide concentration ≥1.0 ng/ml, body mass index ≤40 kg/m² were randomized to receive saxagliptin 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo or metformin 500 mg + placebo for 24 weeks. From weeks 1–5, metformin was uptitrated in 500‐mg/day increments to 2000 mg/day maximum in the saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin and metformin + placebo treatment groups. The main outcome measure was HbA1c change from baseline to week 24. Selected secondary outcomes included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA1c <7% and postprandial glucose area under the curve (PPG‐AUC). Results: At 24 weeks, saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin demonstrated statistically significant adjusted mean decreases vs. saxagliptin 10 mg and metformin monotherapies in HbA1c (?2.5 and ?2.5% vs. ?1.7 and ?2.0%, all p < 0.0001 vs. monotherapy) and FPG (?60 and ?62 mg/dl vs. ?31 and ?47 mg/dl, both p < 0.0001 vs. saxagliptin 10 mg; p = 0.0002 saxagliptin 5 mg + metformin vs. metformin; p < 0.0001 saxagliptin 10 mg + metformin vs. metformin). Proportion of patients achieving an HbA1c <7% was 60.3 and 59.7%, respectively, for saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin (all p < 0.0001 vs. monotherapy). PPG‐AUC was significantly reduced [?21 080 mg·min/dl (saxagliptin 5 mg + metformin) and ?21 336 mg·min/dl (saxagliptin 10 mg + metformin) vs. ?16 054 mg·min/dl (saxagliptin 10 mg) and ?15 005 mg·min/dl (metformin), all p < 0.0001 vs. monotherapy]. Adverse event occurrence was similar across all groups. Hypoglycaemic events were infrequent. Conclusion: Saxagliptin + metformin as initial therapy led to statistically significant improvements compared with either treatment alone across key glycaemic parameters with a tolerability profile similar to the monotherapy components.     

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial

Background/objectives

The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140–199 mg/dL at 120 min (IGT-A) or PG levels 140–199 mg/dL at 120 min and >200 mg/dL at 30/60/90 min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D).

Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study

Background

Levels of faecal elastase-1 (FE-1), a marker of exocrine pancreatic function, are lower in patients with type 2 diabetes than without diabetes. We aimed to investigate the association between FE-1 and nutritional status, gastrointestinal symptoms, and lipid absorption.

Insulin aspart improves meal time glycaemic control in patients with Type 2 diabetes: a randomized, stratified, double-blind and cross-over trial.

AIMS: This randomized, multi-centre, double-blind, stratified, two period, cross-over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of insulin aspart injected immediately before compared with regular human insulin injected 30 min before a Mediterranean-style meal in 37 (23 M, 14 F) patients with Type 2 diabetes. METHODS: Insulin aspart or regular human insulin was given subcutaneously (0.15 U/kg) in random sequence, using a double-dummy technique (at one visit: human regular insulin at t=-30 min and placebo at t=0; at the other visit: placebo at t=-30 min and aspart insulin at t=0). Serum glucose and insulin concentrations (15 points) were measured after each meal for 240 min. RESULTS: Post-prandial glycaemic excursions were 20% lower with insulin aspart (IAsp) compared with regular human insulin (HI) treatment [ratio (Iasp/HI)=0.80, CI=(0.66-0.98), P=0.034]. The maximum serum glucose (SG) concentration was similar for the two treatments (P=NS). The (median) time to maximum SG was 25 min shorter for IAsp compared with HI (P=0.048). Maximum serum insulin concentration was higher after IAsp compared with HI (P=0.023) as well as the area under the 4-h serum insulin curve (P=0.006). Furthermore, the time to maximum serum insulin concentration was 27 min shorter after IAsp (P=0.039), even though IAsp was injected 30 min after HI. No adverse events occurred during the trial. CONCLUSIONS: In patients with Type 2 diabetes a more favourable insulin profile and a better glycaemic control were found with IAsp injected immediately before compared with HI injected 30 min before a Mediterranean-style meal.     

2型糖尿病全天血糖水平与糖化血红蛋白血糖漂移幅度的相关性分析

目的探讨2型糖尿病(T2DM)患者日内不同时间的血糖水平与糖化血红蛋白(HbA1c)及血糖漂移幅度的关系。方法选取2002年12月至2005年10月上海交通大学附属第六人民医院内分泌代谢科新诊断T2DM患者60例,采用动态血糖监测系统(CGMS)进行持续3d的血糖监测并分析日内不同时点、时段的血糖水平、HbA1c、餐后血糖漂移幅度(PPGE)及平均血糖漂移幅度(MAGE)之间的关系。结果(1)T2DM患者HbA1c与全天8次血糖水平均呈显著正相关(r=0.62~0.70,P均<0.01),与PPGE不相关(P>0.05),逐步回归分析显示空腹及中、晚餐后2h血糖进入最后的方程(校正R2=0.566,P<0.01)。(2)HbA1c与全天不同时段的平均血糖水平均呈显著正相关(r=0.57~0.74,P均<0.01),晚餐前1h、晚餐后2~3h及晨300~600时间段的平均血糖水平是其独立影响因素。(3)CGMS所示的日内平均血糖水平与HbA1c相关性最强(r=0.81,P<0.01)。(4)MAGE与HbA1c不相关(P>0.05),三餐PPGE及晨300的血糖水平为影响MAGE的独立参与因素(校正R2=0.427,P<0.01)。结论T2DM患者HbA1c与全天平均血糖水平的关系最密切,而日内血糖的漂移变化主要归因于餐后及夜间血糖的漂移。因此,T2DM的血糖监测及干预治疗应针对全天血糖谱。     

2型糖尿病全天血糖水平与糖化血红蛋白血糖漂移幅度的相关性分析

目的探讨2型糖尿病（T2DM）患者日内不同时间的血糖水平与糖化血红蛋白（HbA1c）及血糖漂移幅度的关系。方法选取2002年12月至2005年10月上海交通大学附属第六人民医院内分泌代谢科新诊断T2DM患者60例，采用动态血糖监测系统（CGMS）进行持续3d的血糖监测并分析日内不同时点、时段的血糖水平、HbA1c、餐后血糖漂移幅度（PPGE）及平均血糖漂移幅度（MAGE）之间的关系。结果（1）他DM患者HbA1c与全天8次血糖水平均呈显著正相关（r=0．62～0．70，P均〈0．01），与PPGE不相关（P〉0．05），逐步回归分析显示空腹及中、晚餐后2h血糖进入最后的方程（校正R^2=0.566，P〈0．01）。（2）HbA1c与全天不同时段的平均血糖水平均呈显著正相关（r=0．57～0．74，P均〈0．01），晚餐前1h、晚餐后2～3h及晨3：00～6：00时间段的平均血糖水平是其独立影响因素。（3）CGMS所示的日内平均血糖水平与HbA1c相关性最强（r=0．81，P〈0．01）。（4）MAGE与HbA1c不相关（P〉0．05），三餐PPGE及晨3：00的血糖水平为影响MAGE的独立参与因素（校正R^2=0．427，P〈0．01）。结论T2DM患者HbA1c与全天平均血糖水平的关系最密切，而日内血糖的漂移变化主要归因于餐后及夜间血糖的漂移。因此，他DM的血糖监测及干预治疗应针对全天血糖谱。     

Addition of canagliflozin to insulin improves glycaemic control and reduces insulin dose in patients with type 2 diabetes mellitus: A randomized controlled trial

The aim of this study was to evaluate the efficacy of canagliflozin in reducing the required insulin dose and the risk of hypoglycaemia in type 2 diabetes (T2D). This study was conducted in patients with T2D treated with insulin. They were randomly assigned to the control (n = 17) and canagliflozin (n = 17, plus 100 mg/day canagliflozin) groups. In both groups, a defined insulin dose adjustment protocol was applied to achieve the same level of glycaemic control. The change from baseline in daily insulin dose was significantly smaller in the canagliflozin group (3.9 units/day) than in the control group (13.4 units/day; P = 0.040). Low blood glucose index and predicted % of blood glucose (BG) <70 mg/dL, which are hypoglycaemia-related variables, worsened significantly in the control group but both remained unchanged in the canagliflozin group. The standard deviation for night-time BG levels improved significantly only in the canagliflozin group. Supplementation of insulin therapy with 100 mg canagliflozin in patients with T2D reduced the required insulin dose and hypoglycaemic risk and flattened night-time glycaemic fluctuations while maintaining the same level of glycaemic control.     

Improved postprandial glycaemic controls with insulin Aspart in type 2 diabetic patients treated with insulin

The effect on postprandial blood glucose control of an immediately pre-meal injection of the rapid acting insulin analogue Aspart (IAsp) was compared with that of human insulin Actrapid injected immediately or 30 before a test meal in insulin-treated type 2 diabetic patients with residual β-cell function. In a double-blind, double dummy crossover design, patients attended three study days where the following insulin injections in combination with placebo were given in a random order: IAsp (0.15 IU/kg body weight) immediately before the meal, or insulin Actrapid (0.15 IU/kg) immediately (Act-₀) or 30 minutes before (Act-₃₀) a test meal. We studied 25 insulin-requiring type 2 diabetic patients, including 14 males and 11 females, with a mean age of 59.7 years (range, 43–71), body mass index 28.3 kg/m² (range, 21.9–35.0), HbA_1c 8.5% (range, 6.8–10.0), glucagon-stimulated C-peptide 1.0 nmol/l (range, 0.3–2.5) and diabetes duration 12.5 years (range, 3.0–26.0). Twenty-two patients completed the study A significantly improved postprandial glucose control was demonstrated with IAsp as compared to Act₀, based on a significantly smaller postprandial blood glucose excursion (IAsp, 899 ± 609 (SD) mmol/l · min versus Act₀, 1102 ± 497 mmol/l min, p < 0.01) and supported by a significantly lower maximum serum glucose concentration (C_max) up to 360 min after dosing (IAsp, 10.8 ± 2.2 mmol/l vs. Act₀, 12.0 ±2.4 mmol/l, p < 0.02). No difference was demonstrated with a meal and Actrapid injected 30 minutes before the meal (AUC_glucose IAsp, 899 ± 609 mmol/l min vs. Act-₃₀, 868 ± 374 mmol/l min; C_max IAsp, 10.8 ± 2.2 mmol/l vs. Act-₃₀, 11.1 ± 1.8 mmol/l). No concerns about the safety of IAsp were raised. Immediate pre-meal administration of the rapid-acting insulin analogue Aspart in patients with type 2 diabetes resulted in an improved postprandial glucose control compared to Actrapid injected immediately before the meal, but showed similar control compared to Actrapid injected 30 minutes before the meal. These results indicate that the improved glucose control previously demonstrated with insulin Aspart compared to human insulin in healthy subjects and type 1 diabetic patients also applies to insulin-treated type 2 diabetic patients. Received: 3 December 1999 / Accepted in revised form: 3 March 2000     

新诊断2型糖尿病患者治疗前后血糖水平的动态变化

目的探查2型糖尿病(T2DM)患者血糖漂移变化的特征。方法选取2002-11~2004-12上海交通大学附属第六人民医院22例新诊断T2DM患者采用动态血糖监测系统(CGMS)对其治疗前后均进行连续3d的血糖监测,进行自身前后对照分析。结果本组患者经2~3周治疗后,糖代谢紊乱明显缓解。22例患者治疗前后平均血糖值[(12.7±2.4)mmol/L对(7.3±0.9)mmol/L];日内血糖最高值[19.5±2.3)mmol/L对(11.0±1.7)mmol/L];血糖漂移最大幅度[(12.1±3.1)mmol/L对(7.1±2.0)mmol/L]。餐前及餐后的平均血糖水平及上述血糖参数之间差异均有显著性意义(P均<0.001)。治疗后血糖>7.8mmol/L及11.1mmol/L的时间百分比与治疗前比较均显著降低[(29(6~64)%对99(37~100)%,3(0~28)%对72(13~100)%,P均<0.001)]。结论动态血糖监测能评估T2DM血糖漂移变化的特征,有助于更有效地控制糖代谢紊乱。     

Dimethylarginines in patients with type 2 diabetes mellitus: relation with the glycaemic control

We tested the relationship between plasma levels of dimethylarginines (ADMA and SDMA) and glycaemic control in 43 type 2 diabetic patients. Type 2 diabetics with poor glycaemic control (HbA1c > 6.5) had significantly lower SDMA and higher ADMA concentrations than those with well-controlled glycaemia (HbA1c < 6.5).     

Improved glycaemic control of thrice-daily biphasic insulin aspart compared with twice-daily biphasic human insulin; a randomized, open-label trial in patients with type 1 or type 2 diabetes

Aim:  This trial evaluated the potential for improving glycaemic control by intensifying a conventional twice-daily therapy with premixed human insulin (HI) to a thrice-daily regimen using premixed formulations of biphasic insulin aspart (BIAsp) in patients with type 1 or type 2 diabetes.
Methods:  This was a multicentre, open-label, parallel group trial. After a 4-week run-in period, patients were randomized 1 : 1 to 16 weeks of treatment. A total of 748 patients were screened, 664 were exposed to trial drug and 604 completed the trial.
Results:  Haemoglobin A_1c, the primary efficacy endpoint, was shown to be significantly lower for the BIAsp treatment group compared with the biphasic HI (BHI) 30 group [estimated mean difference: −0.32, 95% confidence interval (CI) (−0.48; −0.16), p = 0.0001]. The average blood glucose level was significantly lower in the BIAsp group [estimated mean difference: −0.79, 95% CI (−1.17; −0.40), p = 0.0001]. There were few major hypoglycaemic episodes, 11 in the BIAsp group and 7 in the BHI 30 group. Although intensification of insulin therapy with BIAsp three times a day was associated with a higher risk of minor hypoglycaemia (relative risk = 1.58, p = 0.0038), the overall rate of minor hypoglycaemia remained low with both the BIAsp and the BHI treatments (13.1 vs. 8.3 episodes/patient year respectively). Overall safety and patient satisfaction were similar with the two insulin therapies.
Conclusions:  This trial confirmed that a thrice-daily BIAsp regimen can safely be used to intensify treatment for patients inadequately controlled on twice-daily BHI. A treat-to-target trial is required to explore the full potential of the BIAsp regimens and evaluate their use as a viable alternative to intensification with a basal-bolus regimen.     

Culturally sensitive patient-centred educational programme for self-management of type 2 diabetes: A randomized controlled trial

ObjectiveTo assess the effectiveness of a culturally sensitive, structured education programme (CSSEP) on biomedical, knowledge, attitude and practice measures among Arabs with type two diabetes.Research designs and methodsA total of 430 patients with type II diabetes mellitus living in Doha, Qatar were enrolled in the study. They were randomized to either intervention (n = 215) or a control group (n = 215). A baseline and one-year interval levels of biomedical variables including HbA1C, lipid profile, urine for microalbuminuria; in addition to knowledge, attitude and practice (KAP) scores were prospectively measured. The intervention was based on theory of empowerment, health belief models and was culturally sensitive in relation to language (Arabic), food habits and health beliefs. It consisted of four educational sessions for each group of patients (10–20 patients per session), lasting for 3–4 h. The first session discussed diabetes pathophysiology and complications; while the second session discussed healthy life style incorporating the Idaho plate method; and the third session dealt with exercise benefits and goal setting and the fourth session concentrated enhancing attitude and practice using counselling techniques. Outcomes were assessed at base line and 12 months after intervention.ResultsAfter 12 months participation in the intervention was shown to have led to a statistically significant reduction in HbA1C in the (CSSEP) group (?0.55 mmol/L, P = 0.012), fasting blood sugar (?0.92 mmol/L, P = 0.022), body mass index (1.70, P = 0.001) and albumin/creatinine ratio (?3.09, P < 0.0001) but not in the control group. The intervention group also had improvement in Diabetes knowledge (5.9%, P < 0.0001), attitude (6.56%, P < 0.0001), and practice (6.52%, P = 0.0001).ConclusionThis study demonstrates the effectiveness of culturally sensitive, structured, group-based diabetes education in enhancing biomedical and behavioural outcomes in Diabetic patients.