In patients with uncontrolled type 2 diabetes on metformin, once-weekly semaglutide 1.0 mg and once-daily canagliflozin 300 mg significantly improved body composition metrics such as fat and lean mass reduction. While semaglutide demonstrated a numerically greater reduction in fat mass than canagliflozin, the difference was not statistically significant. Both treatments were well tolerated, though gastrointestinal side effects were a notable concern with semaglutide.
PICO Summary
Population:
Adults aged ≥18 with type 2 diabetes, HbA1c 7.0%-10.5%, on stable metformin doses (≥1500 mg or maximum tolerated dose) with eGFR ≥60 mL/min/1.73 m². Exclusions included history of pancreatitis or severe cardiovascular events.
Intervention:
Once-weekly subcutaneous semaglutide 1.0 mg, escalated from 0.25 mg.
Comparison:
Once-daily oral canagliflozin 300 mg.
Outcome:
Efficacy:
- Reductions in fat mass (3.4 kg with semaglutide vs 2.6 kg with canagliflozin).
- No significant differences in lean mass change or fat-to-lean mass ratio.
- Weight loss in the substudy mirrored the main trial (5.3 kg vs 4.2 kg favouring semaglutide).
Safety and Tolerability:
- Both groups had mild adverse events. Semaglutide led to more gastrointestinal side effects.
- No evidence of deleterious changes in body composition (e.g., excessive lean mass loss).
Clinical Summary
Main Finding:
Semaglutide and canagliflozin reduced fat mass and visceral fat comparably, but semaglutide resulted in numerically higher fat loss without statistical significance.
Clinical Relevance:
For patients with type 2 diabetes requiring weight and fat reduction, semaglutide may offer a modest edge in weight management. However, the absence of a placebo group limits conclusions about the unique efficacy of these interventions versus natural variations or alternative treatments.
Study Overview:
- Type of Study: Phase 3B randomised, double-blind trial.
- Sample Size & Population: 178 participants in the substudy, drawn from 788 trial participants.
- Intervention Duration & Doses: 52 weeks; semaglutide dose escalated to 1.0 mg, compared with 300 mg canagliflozin.
- Comparison: Active comparator trial; no placebo.
Outcomes:
Primary Measure (Fat Mass): Reduction of 3.4 kg (semaglutide) vs 2.6 kg (canagliflozin); non-significant difference.
Secondary Measures:
- Lean mass reduction: Semaglutide −2.3 kg; canagliflozin −1.5 kg.
- Visceral fat reduction: Semaglutide −0.2 kg; canagliflozin −0.1 kg.
Safety Profile: Mild gastrointestinal events were higher in semaglutide.
Considerations
The study’s strengths include a robust design and use of DXA imaging. Limitations include a lack of placebo, significant missing data from DXA scans, and the inability of DXA to distinguish certain body composition elements such as muscle vs water.
Reference:
McCrimmon R. et al. (2020). doi:10.1007/s00125-019-05065-8 .
Disclosure:
This summary was created by integrating human and AI expertise to ensure clarity and precision.
