Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised, controlled clinical trial

Rory McCrimmon (Lead / Corresponding author), Andrei-Mircea Catarig, Juan P. Frias, Nanna L. Lausvig, Carel W. le Roux, Desirée Thielke, Ildiko Lingvay

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    Abstract

    Aims/hypothesis: Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of patients from the SUSTAIN 8 phase 3b, randomised, double-blind trial who underwent whole-body dual-energy X-ray absorptiometry (DXA) scanning.

    Methods: Adult patients (age ≥18 years) with type 2 diabetes, HbA1c 53–91 mmol/mol (7.0–10.5%), on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose)
    and with an eGFR ≥60 mL/min/1.73 m2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily and
    semaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans.

    Results: Of the 178 patients in the substudy, numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 and 2.6 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.79 [95% CI: –2.10,
    0.51]). Although total lean mass (baseline 51.3 kg) was also reduced by 2.3 and 1.5 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.78 [95% CI: –1.61,
    0.04]), the proportion of lean mass (baseline 59.4%) increased by 1.2%- and 1.1%-point, respectively (estimated treatment difference 0.14 [95% CI: –0.89, 1.17]). Changes in
    visceral fat mass and overall changes in body composition (assessed by the fat to lean mass ratio) were comparable between the two treatment groups.

    Conclusions/interpretation: In patients with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage.

    Trial registration: NCT03136484 ClinicalTrials.gov identifier.
    Original languageEnglish
    Number of pages13
    JournalDiabetologia
    Early online date2 Jan 2020
    DOIs
    Publication statusPublished - 2 Jan 2020

    Fingerprint

    Body Composition
    Type 2 Diabetes Mellitus
    Randomized Controlled Trials
    Fats
    Therapeutics
    Abdominal Obesity
    Metformin
    Placebos
    Photon Absorptiometry
    Canagliflozin
    semaglutide
    Maximum Tolerated Dose
    Intra-Abdominal Fat
    Insulin Resistance
    Cardiovascular Diseases

    Keywords

    • body composition
    • canagliflozin
    • fat mass
    • glucagon-like peptide receptor agonists
    • randomised controlled trial
    • semaglutide
    • type 2 diabetes
    • weight

    Cite this

    McCrimmon, Rory ; Catarig, Andrei-Mircea ; Frias, Juan P. ; Lausvig, Nanna L. ; le Roux, Carel W. ; Thielke, Desirée ; Lingvay, Ildiko. / Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes : a substudy of the SUSTAIN 8 randomised, controlled clinical trial. In: Diabetologia. 2020.
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    abstract = "Aims/hypothesis: Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of patients from the SUSTAIN 8 phase 3b, randomised, double-blind trial who underwent whole-body dual-energy X-ray absorptiometry (DXA) scanning.Methods: Adult patients (age ≥18 years) with type 2 diabetes, HbA1c 53–91 mmol/mol (7.0–10.5{\%}), on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose)and with an eGFR ≥60 mL/min/1.73 m2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily andsemaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans.Results: Of the 178 patients in the substudy, numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 and 2.6 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.79 [95{\%} CI: –2.10,0.51]). Although total lean mass (baseline 51.3 kg) was also reduced by 2.3 and 1.5 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.78 [95{\%} CI: –1.61,0.04]), the proportion of lean mass (baseline 59.4{\%}) increased by 1.2{\%}- and 1.1{\%}-point, respectively (estimated treatment difference 0.14 [95{\%} CI: –0.89, 1.17]). Changes invisceral fat mass and overall changes in body composition (assessed by the fat to lean mass ratio) were comparable between the two treatment groups.Conclusions/interpretation: In patients with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage.Trial registration: NCT03136484 ClinicalTrials.gov identifier.",
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    author = "Rory McCrimmon and Andrei-Mircea Catarig and Frias, {Juan P.} and Lausvig, {Nanna L.} and {le Roux}, {Carel W.} and Desir{\'e}e Thielke and Ildiko Lingvay",
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    month = "1",
    day = "2",
    doi = "10.1007/s00125-019-05065-8",
    language = "English",
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    Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes : a substudy of the SUSTAIN 8 randomised, controlled clinical trial. / McCrimmon, Rory (Lead / Corresponding author); Catarig, Andrei-Mircea; Frias, Juan P.; Lausvig, Nanna L.; le Roux, Carel W.; Thielke, Desirée; Lingvay, Ildiko.

    In: Diabetologia, 02.01.2020.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes

    T2 - a substudy of the SUSTAIN 8 randomised, controlled clinical trial

    AU - McCrimmon, Rory

    AU - Catarig, Andrei-Mircea

    AU - Frias, Juan P.

    AU - Lausvig, Nanna L.

    AU - le Roux, Carel W.

    AU - Thielke, Desirée

    AU - Lingvay, Ildiko

    PY - 2020/1/2

    Y1 - 2020/1/2

    N2 - Aims/hypothesis: Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of patients from the SUSTAIN 8 phase 3b, randomised, double-blind trial who underwent whole-body dual-energy X-ray absorptiometry (DXA) scanning.Methods: Adult patients (age ≥18 years) with type 2 diabetes, HbA1c 53–91 mmol/mol (7.0–10.5%), on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose)and with an eGFR ≥60 mL/min/1.73 m2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily andsemaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans.Results: Of the 178 patients in the substudy, numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 and 2.6 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.79 [95% CI: –2.10,0.51]). Although total lean mass (baseline 51.3 kg) was also reduced by 2.3 and 1.5 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.78 [95% CI: –1.61,0.04]), the proportion of lean mass (baseline 59.4%) increased by 1.2%- and 1.1%-point, respectively (estimated treatment difference 0.14 [95% CI: –0.89, 1.17]). Changes invisceral fat mass and overall changes in body composition (assessed by the fat to lean mass ratio) were comparable between the two treatment groups.Conclusions/interpretation: In patients with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage.Trial registration: NCT03136484 ClinicalTrials.gov identifier.

    AB - Aims/hypothesis: Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of patients from the SUSTAIN 8 phase 3b, randomised, double-blind trial who underwent whole-body dual-energy X-ray absorptiometry (DXA) scanning.Methods: Adult patients (age ≥18 years) with type 2 diabetes, HbA1c 53–91 mmol/mol (7.0–10.5%), on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose)and with an eGFR ≥60 mL/min/1.73 m2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily andsemaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans.Results: Of the 178 patients in the substudy, numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 and 2.6 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.79 [95% CI: –2.10,0.51]). Although total lean mass (baseline 51.3 kg) was also reduced by 2.3 and 1.5 kg with semaglutide vs canagliflozin (estimated treatment difference: –0.78 [95% CI: –1.61,0.04]), the proportion of lean mass (baseline 59.4%) increased by 1.2%- and 1.1%-point, respectively (estimated treatment difference 0.14 [95% CI: –0.89, 1.17]). Changes invisceral fat mass and overall changes in body composition (assessed by the fat to lean mass ratio) were comparable between the two treatment groups.Conclusions/interpretation: In patients with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage.Trial registration: NCT03136484 ClinicalTrials.gov identifier.

    KW - body composition

    KW - canagliflozin

    KW - fat mass

    KW - glucagon-like peptide receptor agonists

    KW - randomised controlled trial

    KW - semaglutide

    KW - type 2 diabetes

    KW - weight

    UR - https://discovery.dundee.ac.uk/en/publications/5e53458d-7876-4f51-9807-a4b55827d247

    U2 - 10.1007/s00125-019-05065-8

    DO - 10.1007/s00125-019-05065-8

    M3 - Article

    JO - Diabetologia

    JF - Diabetologia

    SN - 0012-186X

    ER -