CoChat
Sign Up
Cited by 150Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Low-Volume Insulin Degludec 200 Units/mL Once Daily Improves Glycemic Control Similarly to Insulin Glargine With a Low Risk of Hypoglycemia in Insulin-Naïve Patients With Type 2 Diabetes

Open access
Gough, Stephen C.L., Bhargava, Anuj, Jain, Rajeev, Mersebach, Henriette, Rasmussen, Søren, Bergenstal, Richard M.·2013·Diabetes Care
DOI 10.2337/dc12-2329PMC PMC3747917
Open this paper in CoChat — free account

Abstract

OBJECTIVE: The 200 units/mL formulation of insulin degludec (IDeg 200 units/mL) contains equal units of insulin in half the volume compared with the 100 units/mL formulation. We compared the efficacy and safety of IDeg 200 units/mL once daily with 100 units/mL insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs. RESEARCH DESIGN AND METHODS: In this 26-week, open-label, treat-to-target trial, subjects (n = 457; mean HbA1c 8.3% [67 mmol/mol], BMI 32.4 kg/m2, and fasting plasma glucose [FPG] 9.6 mmol/L [173.2 mg/dL]) were randomized to IDeg 200 units/mL or IGlar, both given once daily in combination with metformin with or without a dipeptidyl peptidase-4 inhibitor. Basal insulin was initiated at 10 units/day and titrated weekly to an FPG target of <5 mmol/L (<90 mg/dL) according to mean prebreakfast self-measured blood glucose values from the preceding 3 days. RESULTS: By 26 weeks, IDeg reduced HbA1c by 1.30% and was not inferior to IGlar. Mean observed FPG reductions were significantly greater with IDeg than IGlar (−3.7 vs. −3.4 mmol/L [–67 vs. –61 mg/dL]; estimated treatment difference: −0.42 [95% CI −0.78 to −0.06], P = 0.02). Despite this difference, rates of overall confirmed hypoglycemia were not higher with IDeg than with IGlar (1.22 and 1.42 episodes/patient-year, respectively), as were rates of nocturnal confirmed hypoglycemia (0.18 and 0.28 episodes/patient-year, respectively). Mean daily basal insulin dose was significantly lower by 11% with IDeg 200 units/mL compared with IGlar. IDeg was well-tolerated, and the rate of treatment-emergent adverse events was similar across groups. CONCLUSIONS: In this treat-to-target trial in insulin-naïve patients with T2DM, IDeg 200 units/mL improved glycemic control similarly to IGlar with a low risk of hypoglycemia.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/dc12-2329

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • As a result of the treat-to-target design, a comparison can be made in terms of differences in endpoints such as hypoglycaemia (but not, for example, HbA1c).

    “As a result of the treat-to-target design, a comparison can be made in terms of differences in endpoints such as hypoglycaemia (but not, for example, HbA1c), as illustrated in Table 4 [48–54].”

    From A Review of the Pharmacological Properties of Insulin Degludec and Their Clinical Relevance (2014) · cites this paper as [51]

    The Conclusions (page not provided) say that similar HbA1c levels under the treat-to-target design allow comparison of the insulins’ safety profiles, including hypoglycaemia. But the Primary and secondary end points and Statistical analysis sections identify change in HbA1c as the primary endpoint and explicitly compare it between treatments, so the claim’s exclusion of HbA1c is too absolute. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • All phase III trials with IDeg were designed as treat-to-target trials striving for an ambitious fasting blood glucose level target of 4-5 mmol/L (70-90 mg/dL).

    “All of the phase III trials with IDeg were designed as treat-to-target trials striving for an ambitious (fasting) blood glucose level target of 4–5 mmol/L (70–90 mg/dL).”

    From A Review of the Pharmacological Properties of Insulin Degludec and Their Clinical Relevance (2014) · cites this paper as [51]

    The Trial design and Treatments sections (page unavailable) describe this phase 3a IDeg trial as treat-to-target, with a prebreakfast glucose target of <5 mmol/L (<90 mg/dL). The paper does not establish that all phase III IDeg trials used this design or the stated 4–5 mmol/L (70–90 mg/dL) range. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 11

  1. [3]Lane WS Cochran EK Jackson JA High-dose insulin therapy: is it time for U-500 insulin? Endocr Pract 2009; 15: 71– 79 19211405
  2. [4]Crasto W Jarvis J Hackett E Insulin U-500 in severe insulin resistance in type 2 diabetes mellitus. Postgrad Med J 2009; 85: 219– 222 19417173
  3. [8]Zinman B Philis-Tsimikas A Cariou B NN1250-3579 (BEGIN Once Long) Trial Investigators Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care 2012; 35: 2464– 2471 23043166 PMC3507614
  4. [10]Garber AJ King AB Del Prato S; NN1250-3582 (BEGIN BB T2D) Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379: 1498– 1507 22521072
  5. [11]World Medical Association Inc Declaration of Helsinki. Ethical principles for medical research involving human subjects. J Indian Med Assoc 2009; 107: 403– 405 19886379
  6. [12]ICH harmonised tripartite guideline: guideline for good clinical practice. J Postgrad Med 2001; 47: 199– 203 11832625
  7. [13]Workgroup on Hypoglycemia, American Diabetes Association Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005; 28: 1245– 1249 15855602
  8. [15]Unger J Uncovering undetected hypoglycemic events. Diabetes Metab Syndr Obes 2012; 5: 57– 74 22563248 PMC3340111
  9. [16]Marcus A Diabetes care—insulin delivery in a changing world. Medscape J Med 2008; 10: 120 18596953 PMC2438492
  10. [18]Rubin RR Peyrot M Kruger DF Travis LB Barriers to insulin injection therapy: patient and health care provider perspectives. Diabetes Educ 2009; 35: 1014– 1022 19934459
  11. [19]Garg R Johnston V McNally PG Davies MJ Lawrence IG U-500 insulin: why, when and how to use in clinical practice. Diabetes Metab Res Rev 2007; 23: 265– 268 17109474

Cited by

Sorted by citations

Authors
Gough, S. C. L., Bhargava, A., Jain, R., Mersebach, H., Rasmussen, S., & Bergenstal, R. M.
Affiliations
  • NIHR Oxford Biomedical Research Centre (GB)
  • Iowa Diabetes and Endocrinology Research Center (US)
  • Aurora Health Care (US)
  • Novo Nordisk (Denmark) (DK)
  • Park Nicollet Clinic (US)
Corresponding author
Gough, Stephen C.L.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2013-08-13
Volume
36
Issue
9
Pages
2536-2542
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc12-2329
PMC
PMC3747917
OpenAlex
W2101427076
Cited by
150
References
4
Citations by year
2024: 7 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 10 · 2019: 16 · 2018: 20 · 2017: 11 · 2016: 19 · 2015: 22 · 2014: 20 · 2013: 12 · 2012: 1
FWCI
19.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Care (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
insulin degludec, insulin glargine, type 2 diabetes, basal insulin, glycemic control, HbA1c, fasting blood glucose, hypoglycemia, insulin-naive patients, metformin, DPP-4 inhibitors, multiple daily insulin injections
MeSH terms
Aged, Blood Glucose, Diabetes Mellitus, Type 2, Drug Administration Schedule, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Treatment Outcome, Insulin, Long-Acting

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review