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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

Garber, Alan J, King, Allen B, Prato, Stefano Del, Sreenan, Seamus, Balci, Mustafa K, Muñoz-Torres, Manuel, Rosenstock, Julio, Endahl, Lars A +2 more·2012·The Lancet
DOI 10.1016/s0140-6736(12)60205-0
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Abstract

Background Basal insulin therapy does not stop loss of β-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged ≥18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA(1c)) of 7·0-10·0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratified by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3·9-<5·0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA(1c) from baseline to week 52 (non-inferiority limit of 0·4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58·9 years [SD 9·3], diabetes duration 13·5 years [7·3], HbA(1c) 8·3% [0·8], and fasting plasma glucose 9·2 mmol/L [3·1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA(1c) decreased by 1·1% in the degludec group and 1·2% in the glargine group (estimated treatment difference [degludec-glargine] 0·08%, 95% CI -0·05 to 0·21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11·1 vs 13·6 episodes per patient-year of exposure; estimated rate ratio 0·82, 95% CI 0·69 to 0·99; p=0·0359), as were rates of nocturnal confirmed hypoglycaemia (1·4 vs 1·8 episodes per patient-year of exposure; 0·75, 0·58 to 0·99; p=0·0399). Rates of severe hypoglycaemia seemed similar (0·06 vs 0·05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of differences. Rates of other adverse events did not differ between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine. Funding Novo Nordisk.

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  • 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 [52]

  • 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 [52]

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Authors
Garber, A. J., King, A. B., Prato, S. D., Sreenan, S., Balci, M. K., Muñoz-Torres, M., Rosenstock, J., Endahl, L. A., Francisco, A. M. O., & Hollander, P.
Affiliations
  • Baylor College of Medicine (US)
  • Diabetes Care Center (US)
  • University of Pisa (IT)
  • Medical City Dallas Hospital (US)
  • Novo Nordisk (Denmark) (DK)
  • Baylor University Medical Center (US)
Corresponding author
Garber, Alan J
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2012-04
Volume
379
Issue
9825
Pages
1498-1507
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(12)60205-0
OpenAlex
W2917207274
Cited by
325
References
4
Citations by year
2026: 3 · 2025: 1 · 2024: 11 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 12 · 2019: 22 · 2018: 25 · 2017: 25 · 2016: 33 · 2015: 40 · 2014: 40 · 2013: 57 · 2012: 16
FWCI
39.27
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders
Novo Nordisk
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, multiple daily insulin injections, HbA1c, hypoglycemia, beta-cell function, treat-to-target, non-inferiority
MeSH terms
Insulin Glargine, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Drug Administration Schedule, Female, Glycated Hemoglobin, Humans, Male, Middle Aged, Insulin, Long-Acting, Insulin Aspart

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