Transitioning from basal-bolus or premix insulin therapy to a combination of basal insulin and glucagon-like peptide-1 receptor agonist in people with type 2 diabetes.

AIMS: Two fixed-ratio combinations (FRCs) of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) are available for once-daily use in adults with type 2 diabetes. We aimed to review the clinical evidence for the efficacy and safety of changing treatment from a basal-bolus insulin (BBI) regimen or a premix insulin to these combination treatments (fixed-ratio or loose) and provide expert opinion on the practicalities of making such a change. METHODS: Relevant clinical and trial evidence and general review articles were identified through a literature review of ProQuest (comprising BIOSIS Previews®, Current Contents® Search, Embase® and MEDLINE®) for articles published between 2009 and 2021. RESULTS: We identified nine articles reporting the results of FRCs, and seven articles reporting results of loose combinations of basal insulin and GLP-1RAs, in people who transitioned treatment from BBI or premix regimens. In most trials, combination treatment led to improved or equivalent glycaemic control, and a reduction in body weight or BMI, versus the original regimens. Some trials reported a reduction in total insulin dose. A few trials reported reduced or unchanged hypoglycaemia rates, or increased patient satisfaction, with combination therapy where these endpoints were examined. We provide guidance on transitioning of treatment and the patient types most likely to benefit. CONCLUSIONS: In people not achieving glycaemic control with BBI or premix insulin regimens, an FRC or loose combination of basal insulin and GLP-1RA may improve control, decrease the risk of body weight gain or hypoglycaemia and reduce the complexity of treatment.

The relation between the intelligibility of irrelevant speech and cognitive performance-A revised model based on laboratory studies.

Irrelevant background speech causes dissatisfaction and impairs cognitive performance in open-plan offices. The model of Hongisto (2005, Indoor Air, 15, 458-468) predicts the relation between cognitive performance and the intelligibility of speech described with an objectively measured quantity, the Speech Transmission Index (STI). The model has impacted research in psychology and room acoustics as well as the acoustic design guidelines of offices. However, the model was based on scarce empirical data. The aim of this study was to revise the model based on a systematic literature review, focusing on laboratory experiments manipulating the STI of speech by wide-band steady-state noise. Fourteen studies reporting altogether 34 tests of the STI-performance relation were included. According to Model 1 that includes all tests, performance begins to decrease approximately above STI = 0.21 while the maximum decrease is reached at STI = 0.44. Verbal short-term memory tasks were most strongly and very consistently affected by the STI of speech. The model for these tasks showed a deterioration in performance between STI 0.12 and 0.51. Some evidence of an STI-performance relation was found in verbal working memory tasks and limited evidence in complex verbal tasks. Further research is warranted, particularly concerning task-specific effects.

A comparative effectiveness study of degludec and insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes.

AIMS: To compare the real-world effectiveness of insulin degludec (degludec) and glargine 300 units/mL (glargine U300) in insulin-naïve adult patients with type 2 diabetes in routine US clinical practice. MATERIALS AND METHODS: CONFIRM is a non-interventional comparative effectiveness study following US patients across the continuum of care, through electronic medical records from multiple health systems and integrated delivery networks. Propensity-score matching controlled for confounding. The primary endpoint, change in HbA1c from baseline to 180 days of follow-up, was estimated using a repeated-measure of covariance analysis with subject as random effect. Change in the rate of hypoglycaemic episodes (defined using International Classification of Diseases codes 9/10) and change in proportion of patients with hypoglycaemia were estimated using negative binomial and logistic regression, respectively. Time-to-discontinuation of the initial basal insulin/initiation with another prescribed basal insulin was analysed using a Cox Proportional Hazard model. RESULTS: Data concerning 4056 patients were analysed. After matching, baseline characteristics were comparable (n = 2028 in each group). After 180 days of follow-up, degludec was associated with a larger reduction in HbA1c (estimated treatment difference, -0.27%; P = 0.03), greater reductions in change in rate (rate ratio, 0.70; P < 0.05) and greater reductions in change in the likelihood of hypoglycaemia (odds ratio, 0.64; P < 0.01]) compared with glargine U300. In addition, patients treated with degludec were 27% less likely to discontinue treatment at follow-up compared with those treated with glargine U300 (hazard ratio, 0.73; P < 0.001). CONCLUSIONS: Significantly improved HbA1c, larger reductions in rates and likelihood of hypoglycaemia and lower risk of treatment discontinuation were demonstrated with degludec vs glargine U300.

EFFICACY AND SAFETY OF IDEGLIRA IN OLDER PATIENTS WITH TYPE 2 DIABETES.

OBJECTIVE: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years. METHODS: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1-receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V). RESULTS: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% [-1.5; -0.6]95% confidence interval [CI], -0.8% [-1.0; -0.5]95% CI, and -0.9% [-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 [0.2; 1.6]95% CI [ P = .242]; 0.3 [0.1; 0.5]95% CI [ P<.001], and 11.8 [3.3; 42.8]95% CI [ P<.001] for DUAL II, V, and III, respectively). CONCLUSION: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall. ABBREVIATIONS: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes.

Auditory distraction by speech: Comparison of fluctuating and steady speech-like masking sounds.

Sound masking can diminish the performance impairment due to background speech in open-plan offices. This paper compares a steady-state masking sound with the spectrum of the disturbing speech signal to a time-reversed speech masker. As part of a laboratory experiment subjects have to complete a digit span task and a questionnaire. Both masking sounds improve the number recall performance as compared to unmasked speech. When the speech-to-noise ratio is reduced, the error rates decrease only during stationary sound masking. Sound masking with time-reversed speech increases the speech privacy at higher speech-to-noise ratios but it is perceived as more annoying.

Auditory distraction by speech: Sound masking with speech-shaped stationary noise outperforms -5 dB per octave shaped noise.

Sound masking can reduce the distraction due to ambient sounds in open-plan offices. This paper compares a typical masking sound with a slope of -5 dB per octave to a steady-state signal with the spectrum of the disturbing speech signal. Subjects had to complete a number recall task and a questionnaire in a laboratory experiment. The sound conditions with the spectrally-matched noise resulted in similar error rates at 3 dB higher speech-to-noise ratios as compared to the standard noise. Using a speech-shaped steady-state noise as masking sound could reduce the effect of distracting speech in the work place more efficiently.

The impact of road traffic noise on cognitive performance in attention-based tasks depends on noise level even within moderate-level ranges.

Little empirical evidence is available regarding the effects of road traffic noise on cognitive performance in adults, although traffic noise can be heard at many offices and home office workplaces. Our study tested the impact of road traffic noise at different levels (50 dB(A), 60 dB(A), 70 dB(A)) on performance in three tasks that differed with respect to their dependency on attentional and storage functions, as follows: The Stroop task, in which performance relied predominantly on attentional functions (e.g., inhibition of automated responses; Experiment 1: n = 24); a non-automated multistage mental arithmetic task calling for both attentional and storage functions (Exp. 2: n = 18); and verbal serial recall, which placed a burden predominantly on storage functions (Experiment 3: n = 18). Better performance was observed during moderate road traffic noise at 50 dB(A) compared to loud traffic noise at 70 dB(A) in attention-based tasks (Experiments 1-2). This contrasted with the effects of irrelevant speech (60 dB(A)), which was included in the experiments as a well-explored and common noise source in office settings. A disturbance impact of background speech was only given in the two tasks that called for storage functions (Experiments 2-3). In addition to the performance data, subjective annoyance ratings were collected. Consistent with the level effect of road traffic noise found in the performance data, a moderate road traffic noise at 50 dB(A) was perceived as significantly less annoying than a loud road traffic noise at 70 dB(A), which was found, however, independently of the task at hand. Furthermore, the background sound condition with the highest detrimental performance effect in a task was also rated as most annoying in this task, i.e., traffic noise at 70 dB(A) in the Stroop task, and background speech in the mental arithmetic and serial recall tasks.

ICBEN review of research on the biological effects of noise 2011-2014.

The mandate of the International Commission on Biological Effects of Noise (ICBEN) is to promote a high level of scientific research concerning all aspects of noise-induced effects on human beings and animals. In this review, ICBEN team chairs and co-chairs summarize relevant findings, publications, developments, and policies related to the biological effects of noise, with a focus on the period 2011-2014 and for the following topics: Noise-induced hearing loss; nonauditory effects of noise; effects of noise on performance and behavior; effects of noise on sleep; community response to noise; and interactions with other agents and contextual factors. Occupational settings and transport have been identified as the most prominent sources of noise that affect health. These reviews demonstrate that noise is a prevalent and often underestimated threat for both auditory and nonauditory health and that strategies for the prevention of noise and its associated negative health consequences are needed to promote public health.

Higher Derived Time in Range With IDegLira Versus Insulin Glargine U100 in People With Type 2 Diabetes.

BACKGROUND: Derived time in range (dTIR), calculated from self-monitored blood glucose (SMBG-dTIR) profiles, has demonstrated correlation with risk of cardiovascular and microvascular complications. This post hoc analysis of the DUAL V and DUAL VIII trials aimed to compare dTIR with an insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus insulin glargine 100 units/mL (glargine U100) in people with type 2 diabetes (T2D). MATERIALS AND METHODS: Nine-point SMBG profiles were taken more than 24 hours at baseline and end of trial (EOT: 26 weeks [DUAL V] and 104 weeks [DUAL VIII]) and used to derive the percentage of readings within target range (70-180 mg/dL). Estimated treatment differences (ETDs, IDegLira-glargine U100) were analyzed using analysis of covariance, with treatment as fixed effects and baseline response as a covariate. RESULTS: ETDs for change from baseline to EOT in dTIR were significantly greater with IDegLira versus glargine U100 in DUAL V (4.18%, P = .027) and DUAL VIII (5.17%, P = .001). The proportions of people achieving ≥70% dTIR at EOT with IDegLira and glargine U100, respectively, were 62% and 60% in DUAL V (P = .7541), and 50% and 26% in DUAL VIII (P < .0001). The proportion achieving a ≥5% increase in dTIR from baseline to EOT with IDegLira and glargine U100 was 63% in both groups in DUAL V (P = .9043), and 44% and 25%, respectively, in DUAL VIII (P < .0001). CONCLUSIONS: IDegLira was associated with significantly greater increases in dTIR versus basal insulin alone in people with T2D. TRIAL ID(S): ClinicalTrials.gov, NCT01952145 (DUAL V); ClinicalTrials.gov, NCT02501161 (DUAL VIII).

Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable Glucagon-Like Peptide-1 Receptor Agonists in US Clinical Practice (STAY Study).

INTRODUCTION: Reducing dosing frequency may lower treatment burden and improve persistence and adherence. This retrospective, observational study assessed persistence and adherence in patients with type 2 diabetes (T2D) initiating once-weekly or daily injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice. METHODS: The study used data from adults (≥ 18 years) with T2D who were included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre-index and ≥ 365 days post-index, were GLP-1 RA and insulin naïve at first claim (index date) for once-weekly or daily injectable GLP-1 RAs (follow-up: index date + 365 days), and were propensity score (PS) matched 1:1 by baseline characteristics. Persistence, defined as the stay time, was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Adherence was defined as a proportion of days covered of 0.8 or greater. To assess whether patients with more advanced disease would benefit from long-acting treatments, patients were matched to the baseline characteristics of basal insulin initiators using inverse probability of treatment weighting (IPTW). RESULTS: The PS-matched cohorts (n = 784 each) had similar baseline characteristics. Once-weekly regimens were associated with significantly higher persistence than daily treatments (median stay time: 333 vs 269 days; hazard ratio 0.80 [95% confidence interval 0.71, 0.90]; p < 0.01) and with significantly higher adherence than daily regimens at 6 months and 12 months (p < 0.01 for both). Mean glycated haemoglobin reductions were greater with once-weekly than with daily treatment at 6 months (- 1.1% vs - 0.9%; p < 0.01) and 12 months (- 0.9% vs - 0.7%; p = not significant); adherent patients experienced greater reductions than those with poor adherence. Results were similar in the IPTW-matched analysis. CONCLUSION: In US clinical practice, once-weekly injectable treatments are associated with better persistence and adherence than daily regimens over 1 year. Once-weekly regimens may also benefit patients with more advanced T2D.

For people who take medication over a prolonged time, less frequent doses are often more convenient. This can help people to continue with treatment for as long as prescribed (persistence) and to take their medication as prescribed (adherence). This study examined persistence and adherence in people with type 2 diabetes who started treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The GLP-1 RAs in this study are injected under the skin using a small needle. Some types are given daily and others are given once weekly. We used a US database of medical records to identify people with type 2 diabetes who had been prescribed these medications and split them into two groups (784 people each) with similar characteristics. One group had received once-weekly GLP-1 RAs and the other group had received daily GLP-1 RAs. We found that the once-weekly group continued taking their medication for longer (333 days) than the daily group (269 days). People in the once-weekly group were also 20% less likely to stop the treatment too early than those in the daily group. More people in the once-weekly group took their medication as prescribed over 1 year compared with the daily group. The once-weekly group also had larger reductions in blood sugar levels after 1 year than the daily group. People who took their medication as prescribed had the greatest improvements in blood sugar levels. Our results suggest that GLP-1 RAs that are injected less frequently can help people to take their medication as prescribed.

Clinical Considerations When Initiating and Titrating Insulin Degludec/Liraglutide (IDegLira) in People with Type 2 Diabetes.

Therapeutic inertia is a substantial obstacle to the initiation of insulin therapy in people with uncontrolled type 2 diabetes (T2D). This effect has in part been perpetuated by concerns over the impact of a burdensome regimen and the increased risk of hypoglycemia and body weight gain often associated with insulin use. An effective, yet simple, less burdensome regimen with a lower risk of body weight gain and hypoglycemia compared with an insulin-only regimen, may help to address these concerns more effectively. We review the available clinical and real-world data on IDegLira, a once-daily, injectable, fixed-ratio combination of insulin degludec (degludec) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, in people with T2D. Evidence from the comprehensive DUAL clinical trial program suggests an advantage of IDegLira over traditional insulin therapies in a number of clinical outcomes, including maintenance of glycemic control, achievement of glycemic targets, reducing the risk of hypoglycemia, and body weight loss. These findings were demonstrated in participants with T2D irrespective of prior GLP-1RA and insulin use. Furthermore, the individual components of IDegLira have confirmed safety (degludec) or significant benefit in terms of improvement of cardiovascular risk (liraglutide). As an injectable therapy that is simple to titrate, IDegLira has the potential to optimize the ability to achieve relevant glycemic targets, and offers a suitable treatment option for people with T2D requiring insulin therapy who are at risk of hypoglycemia or weight gain.

New Design of a Percutaneous Port System for Continuous Intraperitoneal Insulin Infusion.

Insulin-dependent diabetes mellitus is treated with intensive insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion with insulin pumps. For people with diabetes who cannot achieve acceptable glycemic control despite the use of intensive insulin therapy and continuous glucose measurement, there exists the possibility of continuous intraperitoneal insulin delivery via an implantable pump or a percutaneous port system that is connected to an external insulin pump. In this article, the current second generation of the Accu-Chek® DiaPort system for continuous intraperitoneal insulin delivery with its improvements over the former generation is presented and discussed.

15 Years of Experience with Biphasic Insulin Aspart 30 in Type 2 Diabetes.

Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide, additional studies have been published that highlight new aspects, including use in real-world populations. Evidence from 35 new studies confirms and builds upon previous work indicating that BIAsp 30 continues to have pharmacodynamic and clinical advantages over biphasic human insulin (BHI 30), including in real-world practice with unselected populations of patients. BIAsp 30 has also been shown to be safe and efficacious as an add-on to dipeptidyl peptidase-4 (DPP-4) inhibitors. Intensification with BIAsp 30 is a safe and effective way to improve glycemic control, and titration performed by patients can achieve results that are at least comparable to those when being guided by healthcare providers. Stepwise intensification using BIAsp 30 is comparable to intensification using a basal-bolus regimen, and twice-daily BIAsp 30 provides similar glycemic control to a basal-plus regimen. Data from large observational studies, in particular, have identified patient-related characteristics that are associated with improved clinical responses, suggesting that earlier initiation and intensification of therapy is warranted. Finally, new health-economic analyses continue to confirm that BIAsp 30 is cost effective versus other therapies such as BHI 30, neutral protamine Hagedorn (NPH), or insulin glargine in both insulin-naïve and insulin-experienced patients. After 15 years of clinical use worldwide, analysis of more recent 5-year data indicates that BIAsp 30 remains a safe, effective, and simple-to-use insulin for initiation and intensification by diabetes specialists and primary care physicians in a variety of patients with T2DM.

Exploring the characteristics of suboptimally controlled patients after 24weeks of basal insulin treatment: An individualized approach to intensification.

AIM: To identify characteristics of suboptimally controlled patients with type 2 diabetes (T2DM) on basal insulin treatment who may benefit from intensive titration or further intensification of treatment. METHODS: A post hoc analysis of SOLVE: a 24-week, international, observational study conducted in 17,374 patients with T2DM inadequately controlled on oral antidiabetic drugs (OADs) started on once-daily insulin detemir. Patients were divided into two groups based on whether they achieved HbA1c<7.0% (<53.0mmol/mol) or not at final visit. RESULTS: Suboptimal glycemic control (HbA1c⩾7.0 [⩾53.0mmol/mol]) was independently associated with several baseline characteristics including higher baseline HbA1c (odds ratio [95% confidence interval]: 1.56 [1.50;1.62]; p<0.0001) and body mass index (BMI) (1.03 [1.02;1.04]; p<0.0001), longer duration of diabetes (5-10years: 1.44 [1.25;1.66]; >10years: 1.44 [1.17;1.77]; p<0.0001), and greater number of OADs (two OADs: 1.27 [1.12;1.44]; >2 OADs: 1.38 [1.14;1.66]; p=0.0003). Overall reporting of hypoglycemia was low; fewer patients with HbA1c⩾7.0% (⩾53.0mmol/mol) reported hypoglycemic events compared with patients with HbA1c<7.0% (9.8% vs. 12.5%, respectively; p<0.001). CONCLUSIONS: Baseline characteristics related to severity of disease were strongly associated with suboptimal glycemic control in patients with T2DM receiving basal insulin. These factors may help clinicians in identifying patients who may require an individualized approach to titration or intensification of treatment. TRIAL REGISTRATION: NCT00740519.

SPECTRUM.

BACKGROUND: Optimal usage of continuous glucose monitoring (CGM) requires adequate training of the users. Providing patients with a CGM system without such a training usually doesn't lead to the intended improvement in metabolic control. METHODS: In Germany we developed a structured training program ("SPECTRUM") to ensure a high quality standard for the use of CGM systems. RESULTS: This program is suitably for patients of all age groups and is applicable to all CGM systems and all forms of insulin therapy. A curriculum was also developed so that training centers with less experience with CGM could become capable of offering comprehensive CGM training. CONCLUSIONS: We believe that usage of such a program can be an important step forward in achieving more widespread acceptance and use of CGM systems. Translations in other languages and evaluation with a controlled clinical trial are planned.

Cost-effectiveness of rosiglitazone oral combination for the treatment of type 2 diabetes in Germany.

AIMS/HYPOTHESIS: To assess the cost-effectiveness of rosiglitazone in combination with other oral agents for the treatment of overweight and obese patients with type 2 diabetes in Germany. METHODS: The Diabetes Decision Analysis of Cost--type 2 model was adapted for clinical practice and healthcare financing rules in Germany. The model was calibrated using Cost of Diabetes in Europe Type 2 study data and national statistics. The perspective is that of the sickness funds, and includes all hospital inpatient, ambulatory, rehabilitation, and diabetes therapy, other medications, and sickness leave. The model simulates lifetime treatment histories and associated health outcomes and costs for age and sex-matched cohorts of 1000 overweight and obese patients. The measures of effectiveness used in the analysis were life-years and quality adjusted life-years (QALYs). RESULTS: The combination therapy of rosiglitazone with metformin or sulfonylurea produces better glycaemic control than conventional care of metformin with sulfonylurea and insulin in most patients, extends the viability of oral therapy before requiring insulin, and typically leads to lifetime cost increases across all treatment types. The improvements in glycaemic control lead to survival gains and reductions in morbidity, because of the reduced risk of developing or progressing to later stages of complications. Improvements in morbidity and mortality generate additional QALYs. Costs and health outcomes combine to yield favourable incremental cost-effectiveness ratios, which fall below international 'willingness-to-pay' thresholds in the medium term. CONCLUSION: The model predicts that rosiglitazone in combination with other oral agents is a cost-effective intervention for the treatment of normal weight, overweight and obese patients with type 2 diabetes when compared with conventional care in Germany.

Management of postprandial glucose: Recommended targets and treatment with biphasic insulin.

Increases in glycaemia, particularly following meals, have been independently associated with diabetes complications, most notably cardiovascular disease. Control of postprandial plasma glucose (PPG) therefore plays an important role in diabetes management. International diabetes guidelines acknowledge the value of PPG monitoring yet place relatively little emphasis on PPG control. This article considers the impact of suboptimal PPG control and current recommendations with regard to management of PPG. Specific consideration is given to the role of biphasic insulins, one of the treatment options recognised by the International Diabetes Federation as preferentially lowering PPG levels.

Efficacy of biphasic insulin aspart in patients with type 2 diabetes.

BACKGROUND: It is estimated that 39% of people with diabetes worldwide who use insulin are prescribed premixes, largely because of the practical advantages of addressing both prandial and basal insulin needs with a single product. Rapid-acting premixed insulin analogues such as biphasic insulin aspart 30 (BIAsp 30 [30% soluble insulin aspart and 70% protamine-crystallized insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark) have been developed recently to overcome the pharmacokinetic limitations of regular human insulin used in the most commonly prescribed premix, biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin). It would be expected that these pharmacokinetic improvements would enhance clinical performance. However, the efficacy of BIAsp 30 compared with other common treatment regimens has not yet been systematically reviewed. OBJECTIVE: The aim of this paper is to review current data on the efficacy of BIAsp 30 in comparison with other treatment strategies in type 2 diabetes, including oral antidiabetic drugs (eg, metformin, sulfonylureas, meglitinides, thiazolidinediones), conventional insulins (eg, BHI 30, NPH insulin), and other analogue insulins (eg, insulin glargine, biphasic insulin lispro 25 [Mix 25, 25% biphasic insulin lispro and 75% protaminated lispro]). The focus will be on comparative efficacy (ie, postprandial glucose [PPG], blood glucose profiles, and glycosylated hemoglobin [HbA1c]). METHODS: We identified human clinical studies published through February 2005 involving BIAsp 30 in patients with type 2 diabetes by performing a MEDLINE search (key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin). Additional papers were identified by assessing (1) the reference lists in these studies, (2) published conference proceedings, and (3) our reference files. A total of 21 relevant papers were retrieved: 13 were published as full manuscripts, 1 as a short communication, 5 as abstracts, and 1 as a poster. One paper is currently in press. Novo Nordisk supplied data from an unpublished trial (Study 1536, 2004), as well as data from a trial published in abstract form only (Study 1269, 2002). RESULTS: A regimen of BIAsp 30 BID, at breakfast and dinner, provides improved PPG control compared with BHI 30 BID, NPH BID, and insulin glargine OD for patients with type 2 diabetes. Fasting plasma glucose (FPG) with BIAsp 30 was not significantly different from FPG with insulin glargine; however, FPG was higher with BIAsp 30 than with NPH. BIAsp 30 prevented excessive PPG excursions whether it was injected at the beginning of a meal or < or =15 minutes after starting a meal. BIAsp 30 was not associated with an increased risk of major hypoglycemia compared with other insulin regimens used in the studies reviewed. The incidence of minor hypoglycemic events with BIAsp 30 varied across studies but occurred with frequency or risk similar to BHI 30, Mix 25, or NPH. Treat-to-target trials reported that BIAsp 30 can be used to intensify insulin therapy and to reach the glycemic target recommended by the American Diabetes Association (ie, HbA1c <7.0%). One study reported a greater lowering of postprandial triglyceride levels with BIAsp 30 than with BHI 30. CONCLUSIONS: BIAsp 30 BID can reduce PPG levels to a greater extent than other common treatment regimens, including basal insulin OD. Using BIAsp 30, even once daily, may allow some patients to reach glycemic targets with a degree of convenience and tolerability that may not be achievable with other treatment regimens.