Therapeutics Metabolic and Endocrine Agents
RRM Academy Synopsis
Semaglutide and canagliflozin fat loss did not differ significantly
A 2020 substudy of a randomized, double-blind trial in 178 adults with uncontrolled type 2 diabetes found no significant difference in body composition at 52 weeks between the two drugs it compared. Total fat mass fell by 3.4 kg on semaglutide and 2.6 kg on canagliflozin.
Key Findings
- In the main analysis of 114 participants (semaglutide 53, canagliflozin 61), total fat mass fell by 3.4 kg and 2.6 kg; estimated treatment difference −0.79 kg (95% CI −2.10 to 0.51).
- Lean mass fell by 2.3 kg with semaglutide and 1.5 kg with canagliflozin (estimated treatment difference −0.78 kg, 95% CI −1.61 to 0.04). Its proportion rose by 1.2%-point and 1.1%-point.
- Visceral fat mass decreased by 0.2 kg with semaglutide and 0.1 kg with canagliflozin; estimated treatment difference −0.07 kg (95% CI −0.20 to 0.06).
- About 80% of participants in each treatment group had a lower total fat mass by week 52.
Interpretation
SUSTAIN 8 randomized adults with uncontrolled type 2 diabetes on stable-dose metformin to semaglutide or canagliflozin for 52 weeks. This substudy describes the 178 who had DXA scans (dual-energy x-ray absorptiometry), which split the body into fat mass and fat-free mass. The main analysis used scans from 114 people, and a second analysis of every available scan gave similar results. The authors state that, with no placebo arm, the specific effect of either drug on body composition remains speculative at this stage.
RRM Context
RRM looks for metabolic causes of reproductive conditions. Polycystic ovary syndrome (PCOS), or PMOS (Polyendocrine Metabolic Ovarian Syndrome), is one example, since insulin resistance and visceral fat are part of it. The trial authors link that kind of fat to insulin resistance and to a higher risk of heart and blood vessel disease.
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 participants from the SUSTAIN 8 Phase IIIB, randomised double-blind trial who underwent whole-body dual-energy x-ray absorptiometry (DXA) scanning.
Methods
Adults (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 [1.73 m]-2 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. The study participants and investigator remained blinded throughout the trial, and quality of DXA scans was evaluated in a blinded manner. Change from baseline to week 52 in total fat mass (kg) was the confirmatory efficacy endpoint.
Results
A subset of 178 participants (semaglutide, n = 88; canagliflozin, n = 90) underwent DXA scanning at screening and were randomised into the substudy. Of these, 114 (semaglutide, n = 53; canagliflozin, n = 61) participants had observed end-of-treatment data included in the confirmatory efficacy analysis. Of the 178 participants 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 kg and 2.6 kg with semaglutide and canagliflozin, respectively (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 kg and 1.5 kg with semaglutide and canagliflozin, respectively (estimated treatment difference: -0.78 [-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 [-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 individuals 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
ClinicalTrials.gov NCT03136484.
Funding
This trial was supported by Novo Nordisk A/S, Denmark.
