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Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in J apanese people with type 2 diabetes

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Seino, Yutaka, Terauchi, Yasuo, Osonoi, Takeshi, Yabe, Daisuke, Abe, Nobuyuki, Nishida, Tomoyuki, Zacho, Jeppe, Kaneko, Shizuka·2018·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.13082PMC PMC5813234
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Abstract

Aims: To assess the safety and efficacy of monotherapy with once‐weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). Methods: In this phase IIIa randomized, open‐label, parallel‐group, active‐controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run‐in period) received once‐weekly s.c. semaglutide (0.5 or 1.0 mg) or once‐daily oral sitagliptin 100 mg. The primary endpoint was number of treatment‐emergent adverse events (TEAEs) after 30 weeks. Results: Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide‐ vs sitagliptin‐treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin −1.13%, 95% confidence interval [CI] −1.32; −0.94, and −1.44%, 95% CI −1.63; −1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD −2.22 kg, 95% CI −3.02; −1.42 and −3.88 kg, 95% CI −4.70; −3.07; both P < .0001). Conclusions: In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon‐like peptide‐1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

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  • 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 [12]

    The Results section (Supportive secondary safety endpoints; page unavailable) reports no EAC-confirmed thyroid neoplasms or medullary thyroid carcinomas in this Japanese monotherapy trial. It does not establish the types of adjudicated malignant thyroid neoplasms across the entire SUSTAIN programme, so the programme-wide claim is unsupported. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • 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 [12]

    The Results (Supportive secondary safety endpoints; page unavailable) say calcitonin levels were similar between treatment groups with no apparent change during this Japanese semaglutide-versus-sitagliptin trial. The paper does not establish that the same finding held across the multiple SUSTAIN trials, nor does it specifically report mean calcitonin levels. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Most trials were multinational, except for five that recruited exclusively Japanese participants.

    “Most trials were multinational, except for five that recruited exclusively Japanese participants [39–41, 48, 49].”

    From Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials (2024) · cites this paper as [40]

  • The treatment response observed in our analysis may be influenced by ethnic differences, given that five RCTs recruited exclusively Japanese participants.

    “the treatment response observed in our analysis may also be influenced by ethnic differences, given that five RCTs recruited exclusively Japanese participants [39–41, 48, 49]”

    From Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials (2024) · cites this paper as [40]

  • In most trials, participants received metformin, either as monotherapy or in combination with other agents, except for three trials where participants received no background glucose-lowering therapy after randomisation.

    “in most trials, participants received metformin, either as monotherapy or in combination with other agents, except for three trials where participants received no background glucose-lowering therapy after randomisation [26, 40, 49]”

    From Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials (2024) · cites this paper as [40]

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Authors
Seino, Y., Terauchi, Y., Osonoi, T., Yabe, D., Abe, N., Nishida, T., Zacho, J., & Kaneko, S.
Affiliations
  • Kansai Electric Power (Japan) (JP)
  • Yokohama City University (JP)
  • Naka Memorial Clinic Ibaraki Japan
  • Kyoto University (JP)
  • Abe Clinic Oita Japan
  • Novo Nordisk Pharma Ltd. (Japan) (JP)
  • Takatsuki Red Cross Hospital (JP)
Corresponding author
Seino, Yutaka
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2017-10-05
Volume
20
Issue
2
Pages
378-388
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.13082
PMC
PMC5813234
OpenAlex
W2743930068
Cited by
127
References
7
Citations by year
2026: 12 · 2025: 21 · 2024: 13 · 2023: 14 · 2022: 13 · 2021: 7 · 2020: 23 · 2019: 7 · 2018: 16 · 2017: 1
FWCI
10.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Novo Nordisk (NCT02254291)
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, sitagliptin, type 2 diabetes, monotherapy, Japanese patients, HbA1c, treatment-emergent adverse events, gastrointestinal adverse effects, weight loss, GLP-1 receptor agonists, DPP-4 inhibitors, treatment discontinuation, dose comparison, glycemic control, treatment efficacy and safety, subcutaneous administration, oral administration
MeSH terms
Glucagon-Like Peptide-1 Receptor, Sitagliptin Phosphate, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Administration, Oral, Constipation, Diabetes Mellitus, Type 2, Diarrhea, Dose-Response Relationship, Drug, Drug Administration Schedule, Glucagon-Like Peptides, Follow-Up Studies, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemia, Injections, Subcutaneous, Japan, Nausea, Patient Dropouts, Severity of Illness Index, Weight Loss, Incretins, Dipeptidyl-Peptidase IV Inhibitors

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