For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
36
views
28
references
 Top references
cited by
23
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      181
      similar
       All similar

          The flagship journal of the Society for Endocrinology. Learn more

      • Record: found
      • Abstract: found
      • Article: found

      Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes: a randomised trial

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30).

          Design

          Sixteen-week, open-label, randomised, treat-to-target trial.

          Methods

          Insulin-naive subjects with type 2 diabetes (18–75 years) and a HbA1c of 7–11% were randomised to twice-daily IDegAsp ( n=61), AF ( n=59) or BIAsp 30 ( n=62), all in combination with metformin. Insulin was administered pre-breakfast and dinner (main evening meal) and titrated to pre-breakfast and pre-dinner plasma glucose (PG) targets of 4.0–6.0 mmol/l.

          Results

          Mean HbA1c after 16 weeks was comparable for IDegAsp, AF and BIAsp 30 (6.7, 6.6 and 6.7% respectively). With IDegAsp, 67% of subjects achieved HbA1c <7.0% without confirmed hypoglycaemia in the last 4 weeks of treatment compared with 53% (AF) and 40% (BIAsp 30). Mean fasting PG was significantly lower for IDegAsp vs BIAsp 30 (treatment difference (TD): −0.99 mmol/l (95% confidence interval: −1.68; 0.29)) and AF vs BIAsp 30 (TD: −0.88 mmol/l (−1.58; −0.18)). A significant, 58% lower rate of confirmed hypoglycaemia was found for IDegAsp vs BIAsp 30 (rate ratio (RR): 0.42 (0.23; 0.75)); rates were similar for AF vs BIAsp 30 (RR: 0.92 (0.54; 1.57)). IDegAsp and AF had numerically lower rates of nocturnal confirmed hypoglycaemia vs BIAsp 30 (RR: 0.33 (0.09; 1.14) and 0.66 (0.22; 1.93) respectively).

          Conclusions

          IDegAsp provided comparable overall glycaemic control to BIAsp 30 with a significantly lower rate of hypoglycaemia.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study.

          Craig J Currie, John R Peters, Aodán Tynan … (2010)
          Results of intervention studies in patients with type 2 diabetes have led to concerns about the safety of aiming for normal blood glucose concentrations. We assessed survival as a function of HbA(1c) in people with type 2 diabetes. Two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database from November 1986 to November 2008. We identified 27 965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20 005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly. For combined cohorts, compared with the glycated haemoglobin (HbA(1c)) decile with the lowest hazard (median HbA(1c) 7.5%, IQR 7.5-7.6%), the adjusted hazard ratio (HR) of all-cause mortality in the lowest HbA(1c) decile (6.4%, 6.1-6.6) was 1.52 (95% CI 1.32-1.76), and in the highest HbA(1c) decile (median 10.5%, IQR 10.1-11.2%) was 1.79 (95% CI 1.56-2.06). Results showed a general U-shaped association, with the lowest HR at an HbA(1c) of about 7.5%. HR for all-cause mortality in people given insulin-based regimens (2834 deaths) versus those given combination oral agents (2035) was 1.49 (95% CI 1.39-1.59). Low and high mean HbA(1c) values were associated with increased all-cause mortality and cardiac events. If confirmed, diabetes guidelines might need revision to include a minimum HbA(1c) value. Eli Lilly and Company. Copyright 2010 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 265 times – based on 0 reviews     Review now
            • Record: found
            • Abstract: found
            • Article: not found

            Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes.

            Rury R Holman, Kerensa I. Thorne, Andrew J Farmer … (2007)
            Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited. In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups. A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com].). Copyright 2007 Massachusetts Medical Society.
            Article 0 comments Cited 177 times – based on 0 reviews     Review now
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials

              Bianca Hemmingsen, Søren Lund, Christian Gluud … (2011)
              Objective To assess the effect of targeting intensive glycaemic control versus conventional glycaemic control on all cause mortality and cardiovascular mortality, non-fatal myocardial infarction, microvascular complications, and severe hypoglycaemia in patients with type 2 diabetes. Design Systematic review with meta-analyses and trial sequential analyses of randomised trials. Data sources Cochrane Library, Medline, Embase, Science Citation Index Expanded, LILACS, and CINAHL to December 2010; hand search of reference lists and conference proceedings; contacts with authors, relevant pharmaceutical companies, and the US Food and Drug Administration. Study selection Randomised clinical trials comparing targeted intensive glycaemic control with conventional glycaemic control in patients with type 2 diabetes. Published and unpublished trials in all languages were included, irrespective of predefined outcomes. Data extraction Two reviewers independently assessed studies for inclusion and extracted data related to study methods, interventions, outcomes, risk of bias, and adverse events. Risk ratios with 95% confidence intervals were estimated with fixed and random effects models. Results Fourteen clinical trials that randomised 28 614 participants with type 2 diabetes (15 269 to intensive control and 13 345 to conventional control) were included. Intensive glycaemic control did not significantly affect the relative risks of all cause (1.02, 95% confidence interval 0.91 to 1.13; 28 359 participants, 12 trials) or cardiovascular mortality (1.11, 0.92 to 1.35; 28 359 participants, 12 trials). Trial sequential analyses rejected a relative risk reduction above 10% for all cause mortality and showed insufficient data on cardiovascular mortality. The risk of non-fatal myocardial infarction may be reduced (relative risk 0.85, 0.76 to 0.95; P=0.004; 28 111 participants, 8 trials), but this finding was not confirmed in trial sequential analysis. Intensive glycaemic control showed a reduction of the relative risks for the composite microvascular outcome (0.88, 0.79 to 0.97; P=0.01; 25 600 participants, 3 trials) and retinopathy (0.80, 0.67 to 0.94; P=0.009; 10 793 participants, 7 trials), but trial sequential analyses showed that sufficient evidence had not yet been reached. The estimate of an effect on the risk of nephropathy (relative risk 0.83, 0.64 to 1.06; 27 769 participants, 8 trials) was not statistically significant. The risk of severe hypoglycaemia was significantly increased when intensive glycaemic control was targeted (relative risk 2.39, 1.71 to 3.34; 27 844 participants, 9 trials); trial sequential analysis supported a 30% increased relative risk of severe hypoglycaemia. Conclusion Intensive glycaemic control does not seem to reduce all cause mortality in patients with type 2 diabetes. Data available from randomised clinical trials remain insufficient to prove or refute a relative risk reduction for cardiovascular mortality, non-fatal myocardial infarction, composite microvascular complications, or retinopathy at a magnitude of 10%. Intensive glycaemic control increases the relative risk of severe hypoglycaemia by 30%.
              Article 0 comments Cited 124 times – based on 0 reviews     Review now
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Eur J Endocrinol
                Journal ID (iso-abbrev): Eur. J. Endocrinol
                Journal ID (publisher-id): EJE
                Title: European Journal of Endocrinology
                Publisher: BioScientifica (Bristol )
                ISSN (Print): 0804-4643
                ISSN (Electronic): 1479-683X
                Publication date (Print): August 2012
                Publication date (Electronic preprint): 23 May 2012
                Volume: 167
                Issue: 2
                Pages: 287-294
                Affiliations
                [1]simpleJyväskylä and Medical School, Central Hospital Central Finland simpleUniversity of Eastern Finland KuopioFinland
                [1 ]simpleLi Ka Shing Knowledge Institute, Keenan Research Centre St Michael's Hospital simpleUniversity of Toronto Toronto, OntarioCanada
                [2 ]simplePolish Academy of Sciences simpleCentral Clinical Hospital, MSWiA and Medical Research Center WarsawPoland
                [3 ]simpleThe Third Affiliated Hospital of SUN Yat-Sen University GuangzhouPeople's Republic of China
                [4 ]simpleCerrahpasa Medical School, Istanbul University IstanbulTurkey
                [5 ]simpleUniversity Hospital San Cecilio GranadaSpain
                [6 ]simpleCHU-Guadeloupe Pointe-à-PitreGuadeloupe
                [7 ]simpleNovo Nordisk A/S SøborgDenmark
                [8 ]simpleDepartment of Endocrinology simpleRigshospitalet and Copenhagen University CopenhagenDenmark
                Author notes
                (Correspondence should be addressed to L Niskanen who is now at Department of Medicine, D-tower, 9th floor, Central Hospital Central Finland, Jyväskylä, Finland Email: leo.niskanen@ 123456ksshp.fi )
                Article
                Publisher ID: EJE120293
                DOI: 10.1530/EJE-12-0293
                PMC ID: 3400040
                PubMed ID: 22660026
                SO-VID: e553c0ae-c6a8-47ca-9939-26f59b4956e8
                Copyright © © 2012 European Society of Endocrinology
                License:

                This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 3 April 2012
                Date accepted : 1 June 2012
                Funding
                Funded by: Novo Nordisk
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

                Comments

                Comment on this article

                Related Documents Log
                scite_

                Similar content181

                See all similar

                Cited by23

                See all cited by

                Most referenced authors778

                See all reference authors