Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study

ABSTRACT

Aim: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin ± oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice.

Methods: This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA_1c < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5–10, 10–20 or ≥ 20 years) stratified by prior therapy.

Results: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA_1c decreased ~ 2.2%-points versus ~ 1.6%-points, FPG decreased ~ 4.5?mmol/L versus ~ 2.9?mmol/L and PPPG decreased ~ 6.8?mmol/L versus ~ 5.0?mmol/L. Target HbA_1c was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period.

Conclusions: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.     

Pramlintide and the treatment of diabetes: a review of the data since its introduction

Introduction: Postprandial glucose excursions negatively affect glycemic control and markers of cardiovascular health. Pramlintide, an amylinomimetic, is approved for treatment of elevated postprandial glucose levels in type 1 and type 2 diabetes mellitus.

Areas covered: A literature search of PubMed was conducted to locate articles (up to January 2011) pertaining to original preclinical and clinical research and reviews of amylin and pramlintide. Additional sources were selected from reference lists within articles obtained through the original literature search and from the internet. This article describes the known effects of endogenous amylin and the pharmacodynamics, pharmacokinetics and clinical efficacy of pramlintide. Drug–drug interactions and safety and tolerability are also reviewed.

Expert opinion: Pramlintide significantly reduces hemoglobin A_1c and body weight in patients with type 1 and type 2 diabetes mellitus. Newer research is focusing on weight loss effects of pramlintide and pramlintide plus metreleptin in nondiabetic obese individuals. Preliminary results of these studies are discussed.     

Direct costs and health-related resource utilisation in the 6 months after insulin initiation in German patients with type 2 diabetes mellitus in 2006: INSTIGATE study*

ABSTRACT

Objective: To assess direct costs and describe resource utilisation associated with the first 6 months of insulin therapy in German patients with type 2 diabetes mellitus (DM).

*Results were presented as a poster at the 43rd Congress of the German Diabetes Society, 30?Apr–3?May, 2008, Munich, Germany

Research design and methods: This is an ongoing pan-European, non-interventional, prospective study observing the normal course of diabetes therapy of adult patients with type 2 DM in a diabetologic practice setting, and initiating insulin therapy in 2006. Diabetes therapy 6 months prior to initiation of insulin therapy was assessed retrospectively. For German patients (n?=?256), direct costs associated with health-care resource utilisation prior to and after the insulin initiation were assessed and compared from the German statutory health insurance perspective.

Results: The percentage of patients using blood glucose monitoring increased from 76.4 to 99.6%; 42.1% of patients remained on oral anti-diabetic medication, with metformin used most frequently (36.5%). Total average cost of resource use related to diabetes care per patient for the 6-month period prior to and 6 months after insulin initiation increased from [euro]579 to [euro]961. Mean total costs of diabetes care during 6 months after insulin initiation in the subgroup of obese patients with worse prognosis at baseline (HbA_1c?≥?7.5% and BMI?≥?30?kg/m2) were [euro]1047 [95% CI 965; 1128] vs. [euro]903 [95% CI 840; 965] in other patients.

Conclusions: Resource utilisation and costs related to diabetes increased in the 6 months following insulin initiation, mainly driven by specialist care resource use, insulin, and blood glucose monitoring. Total direct costs of diabetes care of the patients with a less favourable profile of BMI and HbA_1c at baseline are higher compared to other patients.     

Optimizing glycemic control: lixisenatide and basal insulin in combination therapy for the treatment of Type 2 diabetes mellitus

Despite availability of new treatments for patients with Type 2 diabetes mellitus (T2DM), optimal management of glycemic control remains challenging. Treatment with basal insulin can improve HbA_1c, but may not be sufficient to control postprandial plasma glucose (PPG) levels. Both fasting plasma glucose (FPG) and PPG levels contribute to overall glycemic control. In patients with moderate hyperglycemia, PPG excursions have a greater contribution to overall hyperglycemia, with this contribution being greatest when HbA_1c is approximately 7–8% . Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been designed to restore and maintain GLP-1 levels and attenuate PPG excursions. GLP-1RAs that predominantly affect PPG may complement the FPG lowering provided by basal insulin, possibly improving overall glycemic control without additional weight gain and with limited incidence of hypoglycemia. Lixisenatide as an add-on to basal insulin lowers PPG levels, improves HbA_1c control and has a beneficial effect on weight in T2DM patients.     

Clinical significance of targeting postprandial and fasting hyperglycemia in managing type 2 diabetes mellitus

SUMMARY

Measurement of glycosylated hemoglobin (HbA1C) remains the gold standard for the assessment of glycemic control in patients with type 2 diabetes. Recent investigations have studied the correlations between HbA1C levels and other aspects of glucose metabolism, specifically, postprandial glucose (PPG) and fasting plasma glucose (FPG). The results suggest that PPG is also important to overall glycemic control and may be a better index of glucose regulation than FPG. Further, elevated PPG values have been associated with cardiovascular complications and cardiovascular mortality. Such evidence has led to recommendations that PPG levels be monitored as part of type 2 diabetes management, in addition to HbA1C and FPG. These glycemic parameters are differentially affected by the various classes of oral antidiabetic agents used

in the treatment of type 2 diabetes - sulfonylureas, meglitinides, insulin sensitizers and α-glucosidase inhibitors. The sulfonylureas, for example, lower HbA1C, PPG and FPG, while the meglitinides have virtually no effect on FPG. The insulin sensitizer metformin, on the other hand, does not affect PPG levels, whereas the α-glucosidase inhibitors, in the presence of a high-carbohydrate diet, can effectively lower PPG. Many patients receive combination therapy, thereby benefiting from multiple mechanisms of glucose control, although in most cases insulin must later be added to the regimen in order to effectively suppress FPG. Thus, all aspects of glucose metabolism appear to be clinically relevant and should be monitored for effective diabetes management. Further study will more precisely define the clinical significance of PPG.     

Time to pharmacotherapy change in response to elevated HbA1c test results

ABSTRACT

Objective: This study describes the clinical management of type 2 diabetes among a cohort of patients receiving oral antidiabetic monotherapy.

Study design and setting: A retrospective study was conducted within an integrated Midwestern health system that included all individuals receiving oral antidiabetic monotherapy during the period June 1, 1999 to November 30, 2002 (?n = 9335). Among patients with elevated hemoglobin A_1c (HbA_1c) test result(s), Kaplan-Meier estimates of median time until pharmacotherapy change were calculated.

Results: Among the 8068 patients who had ≥ 1 HbA_1c measurement during the study period, 21.4% were at goal (i.e. HbA_1c < 7%). Among patients with at least one elevated test result (≥ 7%), the median time to pharmacotherapy change following an HbA_1c test result of between 7–10% was just over 1 year (372 days, 95% confidence interval [CI] 358–393 days) and 160 days for patients with HbA_1c > 10%. Among patients with at least two elevated tests, the median time to pharmacotherapy change was 275 days from the second test result of between 7–10%, and 70 days among patients with a second HbA_1c > 10%. The median time between HbA_1c testing was 166 days overall, and 154 days among patients with at least one elevated result.

Conclusion: Despite the known benefits of glycemic control among patients with diabetes, the time between elevated HbA_1c results and pharmacotherapy change exceeds 12 months for those with HbA_1c test results between 7–10% and 9 months for those with results over 10%.     

Empagliflozin,a sodium glucose co-transporter 2 inhibitor,in the treatment of type 1 diabetes

Introduction: Available anti-hyperglycemic therapy in type 1 diabetes (T1DM) is currently restricted to insulin, pramlintide, and pancreas or islet cell transplantation. The imperfect replication of normal insulin secretion and glucose control has been a driver for development of other anti-hyperglycemic agents for this population. Empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is currently under investigation as an add-on therapy to insulin in T1DM.

Areas covered: Within the drug evaluation, the authors describe the mechanism of action of SGLT2 inhibitors and preliminary results from studies investigating treatment in rodent models and in individuals with T1DM.

Expert opinion: Studies on adjunct therapeutic effects of empagliflozin in individuals with T1DM are limited, but initial reports show favorable effects on reducing HbA1c, body weight, total daily insulin dose and hypoglycemic events. Intriguingly, this drug may confer a degree of renal protection by reducing glomerular hyperfiltration that can arise in the diabetic state. Currently, the primary concern seems to be the presence of ketone levels indicating an under-insulinized state. Long-term effects can only be inferred from studies in type 2 diabetes mellitus at this time. Empagliflozin represents a novel non-insulin-mediated therapy that warrants further investigation.     

Transferring type 2 diabetes patients with uncontrolled glycaemia from biphasic human insulin to biphasic insulin aspart 30: experiences from the PRESENT study

ABSTRACT

Aim: The Physician's Routine Evaluation of Safety and Efficacy of NovoMix* 30 Therapy (PRESENT) aims to assess the safety and efficacy of biphasic insulin aspart (BIAsp30) used in routine clinical practice.

Methods: This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Efficacy endpoints included changes in HbA_1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), and proportion who achieved target HbA_1c <?7%. Changes from baseline were analysed using paired t-test. Safety endpoints were incidence and rate of hypoglycaemic episodes. A subgroup of patients previously uncontrolled (HbA_1c ≥?7.0%) on biphasic human insulin (BHI) were analysed.

Results: Glycaemia improved significantly (mean ± SD): HbA_1c by 1.58 ± 1.69% points (from 9.32 ± 1.64% to 7.70 ± 1.29%), FPG by 2.92 ± 3.71?mmol/L and PPPG by 4.75 ± 4.87?mmol/L. The incidence of hypoglycaemic episodes decreased over time, from 38.7% (baseline) to 20.8% (6?months). Episodes were mostly minor (reduced from 37.7 to 20.6% at 6?months), occurring during the day (reduced from 31.5 to 17.1% at 6?months). Major episodes were less frequently reported (reduced from 5.0 to 0.4% at 6?months). The rate of hypoglycaemia (episodes/patient year) from baseline to end of study decreased over time for overall (8.9–2.2), major (0.7–0.1), minor (8.2–2.2) and nocturnal (2.9–0.5) episodes.

Conclusions: In this observational study, in the type 2 diabetes mellitus patients who were poorly controlled on BHI, glycaemia improved when transferred to BIAsp30, and a lower incidence or rate of hypoglycaemia was observed in these patients.     

Targeting the pathophysiology of type 2 diabetes: rationale for combination therapy with pioglitazone and exenatide

ABSTRACT

Objective: The objectives of this article are to review the pathophysiology of type 2 diabetes mellitus (T2DM), present the rationale for a pathophysiologically based treatment approach for patients with T2DM and discuss the role of the therapeutic combination of pioglitazone and exenatide in the management of T2DM.

Methods: References were identified from searches of the PubMed database that were conducted in May 2007, October 2007 and March 2008 and updates to product labeling that occurred between May 2007 and December 2007. Information was selected for inclusion on the basis of its relevance to the pathophysiology of T2DM or the clinical use of thiazolidinediones or exenatide. Discussion of other anti-diabetic treatment strategies is not included.

Results: T2DM results from a combination of insulin resistance and beta-cell dysfunction. The combination of a thiazolidinedione and an incretin mimetic offers a combination of characteristics (e.g., glycemic control, reduced insulin resistance, decreased weight, potential cardiovascular benefits, beta-cell preservation) that addresses many of the pathophysiologic underpinnings of T2DM. A recent small placebo-controlled study assessed the effects of exenatide used with a thiazolidinedione (TZD; pioglitazone or rosiglitazone) with or without metformin. Exenatide demonstrated a greater incidence of glycosylated hemoglobin (HbA_1c) <?7%; greater reductions in fasting blood glucose, postprandial plasma glucose and body weight; and improved beta-cell function versus the TZD/placebo group. However, exenatide was associated with a high dropout rate, and the 16-week duration of treatment in this study precluded evaluation of the long-term effects of the exenatide/pioglitazone combination. Furthermore, exenatide/pioglitazone has not been compared with any other anti-diabetic combination in a head-to-head clinical study.

Conclusions: Dual effects on insulin sensitivity (TZD) and insulin secretion (exenatide) make the TZD/exenatide combination a rational treatment option for patients who do not attain glycemic control with a single agent. Studies undertaken to evaluate the effects on cardiovascular outcomes and the potential for prevention of T2DM with impaired glucose tolerance may reveal additional advantages of this combination approach.     

罗格列酮联合胰岛素治疗2型糖尿病的临床疗效观察

目的观察罗格列酮应用于单用胰岛素治疗血糖控制欠佳的2型糖尿病患者的疗效及安全性。方法102例2型糖尿病患者,随机分成两组:单用胰岛素治疗组(DM+INS组)50例,联合治疗组(DM+INS+RSG组)治疗组52例,在继续应用胰岛素治疗的基础上加服罗格列酮(Rosiglitazone,RSG)4mg/d,共三个月。观测两组治疗前后空腹血糖(FPG)及餐后血糖(PPG)、糖化血红蛋白(HgA1C)、甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白(HDLC)、低密度脂蛋白(LDLC)和体重指数(BMI)的改变。结果DM+INS+RSG组与DM+INS组治疗前FPG、PPG、HbA1C、TC、TG、HDLC、LDLC和胰岛素用量无明显统计学差异(P>0.05)。DM+INS+RSG组治疗后1个月和3个月FPG、PPG、HbA1C均有明显的下降(P<0.05,P<0.01)。结论对单用胰岛素治疗血糖控制欠佳的2型糖尿病患者可加用胰岛素增敏剂罗格列酮治疗,可使血糖和糖化血红蛋白得以良好的控制。     

Association between incidence of acute exacerbation and medication therapy in patients with COPD

ABSTRACT

Objective: To provide an overview of the incidence of type 2 diabetes in children and adolescents and provide direction for clinicians who care for children and adolescents.

Research design and method: The data presented in this review were obtained from published literature and abstracts presented at scientific meetings. Clinical trials and review articles were identified using the search terms ‘metabolic syndrome’, ‘type 2 diabetes mellitus’, ‘children’, and ‘adolescents’ in a MEDLINE search from 1995–2005. Additionally, the bibliographies of the identified articles were reviewed.

Results: Type 2 diabetes is rising rapidly in children and adolescents worldwide. Changing a child's living environment to include physical activity, and a well balanced, low fat, high fiber diet, are important for the maintenance of a desirable body weight and improving insulin sensitivity. Maintaining euglycemia with metformin, sulfonylureas, thiazolinediones, and insulin is recommended. Effective treatment of co-morbid problems such as hypertension and dyslipidemia can decrease the risk of cardiovascular complications.

Conclusions: The prevalence of type 2 diabetes in children will continue to rise until effective measures are taken to prevent obesity in this age group. Ensuring that children have a well-balanced low fat, high fiber, diet, combined with physical activity, will promote weight loss or maintenance, improve insulin sensitivity, and decrease the risk of diabetes and cardiovascular disease. Pharmacologic therapy is recommended for children who are unable to achieve satisfactory glycemic control through physical activity and diet.     

Cost-effectiveness of insulin aspart compared to human insulin in pregnant women with type 1 diabetes in the UK

ABSTRACT

Objectives: In women with type 1 diabetes, poor glycaemic control during pregnancy is associated with high risk of pre-term delivery, perinatal mortality and morbidity. This economic analysis utilises clinical effectiveness data from the Insulin Aspart Pregnancy Study Group Trial to assess costs and outcomes associated with insulin aspart (IAsp) and human insulin (HI) as part of a basal-bolus insulin regimen in pregnant women with type 1 diabetes in the UK.

Research design and methods: Women with type 1 diabetes were enrolled if ≤?10 weeks pregnant or planning to become pregnant, and had HbA_1c ≤?8% at confirmation of pregnancy. Subjects were randomised to treatment with IAsp or HI in a basal-bolus regimen with NPH insulin, with doses titrated according to American Diabetes Association guidelines. An effectiveness endpoint, retrospectively defined for this analysis, was the percentage of women with a live birth at term (≥37 weeks’ gestation). We considered costs of insulin, adverse events, delivery, and neonatal care for pre-term infants. Expected need for neonatal care was estimated from gestational age, using data from the literature and a large UK hospital. Costs were calculated from the perspective of the UK National Health Service.

Results: A total of 322 pregnant women were enrolled in the study and the outcome of pregnancy was known for 302, 151 in each arm. More women experienced a live birth at term with IAsp (72.8%) than with HI (60.9%), difference 11.9% (95% CI 2.0%, 22.5%, p?=?0.028). Mean cost per woman was £3222 for IAsp and £3539 for HI, difference ?£318 (95% CI ?£1353, £576; p?=?0.49).

Conclusions: Compared with HI, the use of IAsp in pregnant women with type 1 diabetes resulted in more live births at term, without increasing total costs of treatment. A prospectively defined study is required to confirm these conclusions.     

Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind,cross-over,clinical trial

ABSTRACT

Objective: To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea–metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients.

Research design and methods: After a 4-week run-in period with a suplonylurea–metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6?mg/day (2?mg three times a day) or acarbose, up to 300?mg/day (100?mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA_1c), fasting plasma glucoe (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assesssment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment.

Results: Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA_1c (?1.1%, p?<?0.05), FPG (?9.5%, p?<?0.05), and PPG (?14.9%, p?<?0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p?<?0.05), BMI (+3.3%, p?<?0.05) and FPI (+22.5%, p?<?0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (?1.9%, p?<?0.05), BMI (?4.1%, p?<?0.05), HbA_1c (?1.4%, p?<?0.05), FPG (?10.7%, p?<?0.05), PPG (?16.2%, p?<?0.05), FPI (?16.1%, p?<?0.05), PPI (?26.9%, p?<?0.05), HOMA index (?30.1%, p?<?0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA_1c, FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (?16.1% vs. +22.5%, respectively, p?<?0.05) and HOMA index (?30.1% vs. +2.7%, p?<?0.05).

Conclusion: In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.     

The effectiveness of insulin initiation regimens in patients with type 2 diabetes mellitus: a large national medical records review study comparing a basal insulin analogue to premixed insulin*

ABSTRACT

Objectives: The objective of the study was to compare the level of HbA_1c reduction between a once-daily basal insulin analogue (glargine, GLG) and two twice-daily premixed insulin analogue formulations (premixed insulin lispro 75/25, PIL; premixed human insulin 70/30, PHI) in patients with type 2 diabetes mellitus (T2DM) initiating insulin therapy.

Research design and methods: Data were extracted from a US national medical records database for this retrospective, 18-month, observational, cohort study. Patients with T2DM were initiated on GLG (n = 3624), PIL (n = 895) or PHI (n = 3647). A combined premixed insulin group (CPI; n = 4542) was formed for data analyses. Propensity score methods were used to adjust for 19 baseline characteristics.

Main outcome measures: Adjusted and unadjusted reductions in HbA_1c at six time points post-insulin initiation for a period of 18 months.

Results: Reductions in mean HbA_1c relative to baseline were demonstrated by all cohorts for all treatment periods. After adjusting for baseline differences, the CPI cohort consistently demonstrated greater reductions in HbA_1c (0.04–0.14%; p < 0.05), compared to the GLG cohort. The PIL cohort consistently demonstrated the greatest reductions in HbA_1c (0.26–0.65%; p < 0.05), compared to the GLG cohort.

Limitations: Retrospective study design and vulnerabilities to patient drop-outs.

Conclusions: In clinical practice settings, greater reductions in HbA_1c were found in patients with premixed insulin than with a basal insulin analogue with the greatest reduction observed with premixed insulin lispro 75/25, confirming the observations of randomized, controlled trials.     

In-hospital treatment of hyperglycemia: effects of intensified subcutaneous insulin treatment

ABSTRACT

Background: Hyperglycemia is common in hospitalized patients; however, glycemic control obtained during hospitalization is often suboptimal. No methods for achievement of proper glycemic control in this population have been validated in the in-hospital setting.

Aims: To study the effect of a novel intensive subcutaneous insulin protocol on the quality of in-hospital glycemic control.

Methods: Included in this prospective controlled study were all diabetic patients admitted to the internal medicine departments in a tertiary medical center during a 1-year period. The study was divided into pre-intervention (n = 94), intervention (n = 102) and post-intervention (n = 79) periods. During the intervention period all hospitalized diabetic patients with blood glucose >?200?mg/dL were treated with an intensive multi-injection protocol consisting of two or four times daily regular/NPH insulin injections.

Results: Mean glucose level throughout hospitalization was 178.7 ± 47?mg/dL in the intervention period versus 198.8 ± 60?mg/dL in the pre-intervention period (?p < 0.05). During the intervention period, the difference between mean admission and discharge day glucose levels was 43?mg/dL in patients treated with four times daily insulin injections, in contrast to no change noted in the other treatment groups. During the post-intervention period the rate of implementation of the intensive protocol by the internal medicine teams declined to 47.5%, in contrast to a 78.4% implementation rate during the intervention period. This decline was associated with deterioration of glycemic control.

Conclusions: The use of intensified insulin regimen improved the glycemic control of hospitalized diabetic patients. Successful incorporation of such intensive protocols into daily medical routines requires close involvement and continuous physician guidance by the hospital diabetes team.     

Long-term efficacy of insulin glargine therapy with an educational programme in type 1 diabetes patients in clinical practice

ABSTRACT

Objective: To investigate the effect of initiating insulin glargine (glargine: LANTUS*), a once-daily basal insulin analogue, plus an educational programme, on glycaemic control and body weight in patients with type 1 diabetes in clinical practice.

Research design and methods: A retrospective analysis of the medical records of 65 patients (mean age: 40.7 ± 13.3 years) with type 1 diabetes was performed. Patients had previously been treated with NPH insulin (NPH; n = 54) or NPH insulin + lente insulin (NPH + lente; n = 11) and then received glargine once daily (bedtime), plus short-acting prandial insulin, for 30 months. Before initiation of glargine, patients participated in a diabetes educational programme and then received physician consultations throughout the study. Metabolic control, body weight and severe hypoglycaemia data were analysed at 9 and 30 months.

Results: Following initiation of glargine, patients showed a decrease in HbA_1c from 7.29 ± 1.1% to 7.06 ± 1.0%; p < 0.01 at 30 months. When the results were analysed by pre-treatment, both NPH-pre-treated and NPH+lente-pre-treated patients showed a significant reduction in HbA_1c of 0.14% and 0.82%, respectively, at 30 months (7.27 ± 1.2% to 7.13 ± 1.1% and 7.42 ± 1.2 to 6.60 ± 0.3%, respectively; p < 0.01). No change in body weight was observed in the overall group. No episodes of severe hypoglycaemia (blood glucose <?40?mg/dL [<?2.2?mmol/L] occurred.

Conclusions: In this retrospective study of medical records, patients with type 1 diabetes treated with insulin glargine over 30 months in combination with educational support and close clinical supervision decreased their HbA_1c levels without weight gain versus previous treatment with NPH insulin or insulin lente. Further studies in a larger cohort of patients would help to confirm these results.     

Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes

ABSTRACT

Objective: The purpose of this study was to evaluate the efficacy and safety of sitagliptin as an add-on to metformin therapy in patients with moderately severe (hemoglobin A_1c ≥?8.0% and ≤?11.0%) type 2 diabetes mellitus (T2DM).

Research design and methods: This was a multi­national, randomized, placebo-controlled, parallel-group, double-blind study conducted in 190 patients with T2DM. After ≥?6?weeks of stable metformin monotherapy (≥?1500?mg/day), patients were randomized to either the addition of sitagliptin 100?mg once daily or placebo to ongoing metformin for 30?weeks.

Main outcome measures: The primary efficacy endpoint was reduction in hemoglobin A_1c (HbA_1c) measured after 18?weeks of sitagliptin treatment. Key secondary end­points included reduction in fasting plasma glucose (FPG) and 2-hour (2-h) postprandial plasma glucose (PPG) at 18 weeks, and HbA_1c at 30 weeks. The proportion of patients meeting the goal of HbA_1c <?7.0% was also analyzed.

Results: Sitagliptin significantly reduced HbA_1c, FPG, and 2-h PPG, compared with placebo (all p < 0.001). The net improvement in HbA_1c was –1.0% at both 18 and 30 weeks, and a significantly greater proportion of patients treated with sitagliptin achieved HbA_1c <?7.0% by the end of the study (22.1% vs. 3.3%, p < 0.001). Sitagliptin was well-tolerated. Compared with placebo, sitagliptin had a neutral effect on body weight and did not signif­icantly increase the risk of hypoglycemia or gastro­intestinal adverse events.

Conclusions: Addition of sitagliptin 100?mg once daily to ongoing metformin therapy was well-tolerated and resulted in significant glycemic improvement in patients with moderately severe T2DM who were treated for 30 weeks.

Trial registration: ClinicalTrials.gov identifier: NCT00337610.     

Intermediate and long-acting insulins: a review of NPH insulin,insulin glargine and insulin detemir

ABSTRACT

Objective: To review intermediate- and long-acting insulins with specific emphasis on the newer insulin analogs.

Methods: A MEDLINE search, in English, was conducted with a cut-off of June 30, 2006, using the terms ‘NPH insulin’, ‘insulin analogs’, ‘insulin glargine’, ‘insulin detemir’ and ‘long-acting insulins’. All clinical trials from within the search period were included.

Results: The insulin analogs, insulin glargine and insulin detemir, were introduced in an attempt to improve glycemic control among patients with diabetes, without increasing the risk of hypoglycemia. This review indicates that both insulin analogs demonstrate better glycemic control than NPH insulin, based on measurements of HbA_1c, fasting glucose and intra-subject variability in blood glucose. This was accomplished with similar or reduced risk of hypoglycemia. Also, insulin detemir appears to be associated with less body weight increase than NPH insulin or insulin glargine.

Conclusion: The newer long-acting insulin analogs, insulin detemir and glargine, appear to provide better glycemic control than NPH insulin without increasing the risk of hypoglycemia.