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Cited by 132Diabetes Treatment and ManagementDiabetes Management and ResearchPharmacology and Obesity Treatment

Safety and efficacy of once‐weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: A randomized trial

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Kaku, Kohei, Yamada, Yuichiro, Watada, Hirotaka, Abiko, Atsuko, Nishida, Tomoyuki, Zacho, Jeppe, Kiyosue, Arihiro·2018·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.13218PMC PMC5969242
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Abstract

Aim: To evaluate the safety and efficacy of once‐weekly subcutaneous semaglutide as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional OAD added to background therapy in Japanese people with type 2 diabetes (T2D) inadequately controlled on diet/exercise or OAD monotherapy. Methods: In this phase III, open‐label trial, adults with T2D were randomized 2:2:1 to semaglutide 0.5 mg or 1.0 mg, or one additional OAD (a dipeptidyl peptidase‐4 inhibitor, biguanide, sulphonylurea, glinide, α‐glucosidase inhibitor or thiazolidinedione) with a different mode of action from that of background therapy. The primary endpoint was number of adverse events (AEs) after 56 weeks. Results: Baseline characteristics were balanced between treatment arms (601 randomized). More AEs were reported in the semaglutide 0.5 mg (86.2%) and 1.0 mg (88.0%) groups than in the additional OAD group (71.7%). These were typically mild/moderate. Gastrointestinal AEs were most frequent with semaglutide, which diminished over time. The mean glycated haemoglobin (HbA1c) concentration (baseline 8.1%) was significantly reduced with semaglutide 0.5 mg and 1.0 mg vs additional OAD (1.7% and 2.0% vs 0.7%, respectively; estimated treatment difference [ETD] vs additional OAD −1.08% and −1.37%, both P < .0001). Body weight (baseline 71.5 kg) was reduced by 1.4 kg and 3.2 kg with semaglutide 0.5 mg and 1.0 mg, vs a 0.4‐kg increase with additional OAD (ETD −1.84 kg and −3.59 kg; both P < .0001). For semaglutide‐treated participants, >80% achieved an HbA1c concentration <7.0% (Japanese Diabetes Society target). Conclusions: Semaglutide was well tolerated, with no new safety issues identified. Semaglutide treatment significantly reduced HbA1c and body weight vs additional OAD treatment in Japanese people with T2D.

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  • In the SUSTAIN program, serum calcitonin was measured and no notable difference in mean levels was seen between treatment arms.

    “Serum calcitonin was measured during these trials, and no notable difference in mean levels was seen between the treatment arms.”

    From Safety of Semaglutide (2021) · cites this paper as [13]

    The Results (Safety endpoints) report that calcitonin levels were consistently low and similar across all treatment groups in this Japanese trial. That supports the comparison for this trial, but the passage does not establish the same finding across the broader SUSTAIN program or report mean levels specifically. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • None of the adjudicated malignant thyroid neoplasms in the SUSTAIN program were medullary carcinoma.

    “None of these were medullary carcinoma.”

    From Safety of Semaglutide (2021) · cites this paper as [13]

    The Results (Safety endpoints; page not provided) report no medullary thyroid carcinoma among the adjudicated neoplasms in this Japanese trial. The paper does not establish that none occurred across the entire SUSTAIN program. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In the SUSTAIN program, three adjudicated events of malignant thyroid neoplasm were identified: two in semaglutide-treated patients (combined n = 5,933) and one in the comparator group (n = 4,736).

    “In the SUSTAIN program, three adjudicated events of malignant thyroid neoplasm were identified, two in semaglutide-treated patients (combined n = 5,933), and one in the comparator group (n = 4,736)”

    From Safety of Semaglutide (2021) · cites this paper as [13]

    The Results (Safety endpoints; page unavailable) report adjudicated neoplasms in this Japanese trial and state that no medullary thyroid carcinoma occurred. Our copy does not report the claimed three malignant thyroid neoplasms across the SUSTAIN program or the group sizes of 5,933 and 4,736; searches for those counts and thyroid malignancies found no supporting passage. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 15

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Authors
Kaku, K., Yamada, Y., Watada, H., Abiko, A., Nishida, T., Zacho, J., & Kiyosue, A.
Affiliations
  • Kawasaki Medical School (JP)
  • Akita University (JP)
  • Juntendo University (JP)
  • Asahikawa Medical University (JP)
  • Novo Nordisk Pharma Ltd. (Japan) (JP)
  • Department of Internal Medicine Tokyo‐Eki Center‐Building Clinic Tokyo Japan
Corresponding author
Kaku, Kohei
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2018-02-21
Volume
20
Issue
5
Pages
1202-1212
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.13218
PMC
PMC5969242
OpenAlex
W2784318050
Cited by
132
References
3
Citations by year
2026: 15 · 2025: 25 · 2024: 11 · 2023: 15 · 2022: 11 · 2021: 8 · 2020: 27 · 2019: 6 · 2018: 14
FWCI
10.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Novo Nordisk A/S
  • ClinicalTrials.gov (NCT02207374)
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 › Pharmacology › Pharmacology and Obesity Treatment
Keywords
semaglutide, type 2 diabetes, inadequate glycemic control, oral antidiabetic drugs, combination therapy, HbA1c, weight loss, gastrointestinal adverse effects, drug safety, Japanese patients, GLP-1 receptor agonists, monotherapy, sulfonylureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors
MeSH terms
Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Administration, Oral, Aged, Combined Modality Therapy, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Resistance, Drug Therapy, Combination, Glucagon-Like Peptides, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Injections, Subcutaneous, Japan, Male, Middle Aged, Weight Loss, Drug Monitoring

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