In adults with type 2 diabetes inadequately controlled with metformin, semaglutide 1.0 mg once weekly significantly reduced HbA1c and body weight compared to daily canagliflozin 300 mg, though semaglutide was associated with higher rates of gastrointestinal side effects.
PICO Summary
Population:
Adults (n=788) aged ≥18 years with type 2 diabetes, HbA1c levels 7.0–10.5%, BMI ≥25, on stable metformin for ≥90 days.
Intervention:
Semaglutide 1.0 mg, subcutaneous injection once weekly.
Comparison:
Canagliflozin 300 mg, oral administration once daily.
Outcome:
Efficacy:
• HbA1c reduction: Semaglutide (-1.5%) vs Canagliflozin (-1.0%), ETD -0.49% (p<0.0001).
• Weight loss: Semaglutide (-5.3 kg) vs Canagliflozin (-4.2 kg), ETD -1.06 kg (p=0.0029).
Safety and Tolerability:
• Adverse events: Higher rates of gastrointestinal disorders with semaglutide (46.9% vs 27.9%) and infections with canagliflozin (34.5% vs 29.1%).
• Discontinuation due to side effects: 9.7% with semaglutide vs 5.1% with canagliflozin.
Clinical Summary
Main Finding:
Semaglutide demonstrated superior efficacy in HbA1c reduction and weight loss compared to canagliflozin in patients with uncontrolled type 2 diabetes on metformin. However, semaglutide was associated with more frequent gastrointestinal adverse events.
Clinical Relevance:
This study informs treatment intensification decisions in type 2 diabetes, showcasing semaglutide’s efficacy in achieving glycaemic and weight targets. Despite gastrointestinal side effects, its benefits may make it a preferred second-line therapy for certain patients, especially those prioritising weight management and glucose control.
Study Overview:
- Type of Study: Double-blind, randomised, controlled phase 3b trial.
- Sample Size & Population: 788 adults with type 2 diabetes on stable metformin.
- Intervention Duration & Doses: 52 weeks of semaglutide (1.0 mg weekly) vs canagliflozin (300 mg daily).
- Comparison: Placebo-controlled, double-dummy design.
Outcomes:
Primary Measure (HbA1c):
- Semaglutide resulted in a greater reduction in HbA1c from baseline (-1.5%) compared to canagliflozin (-1.0%), with an estimated treatment difference (ETD) of -0.49% (95% CI: -0.65 to -0.33, p<0.0001).
- A significantly higher proportion of patients achieved the American Diabetes Association (ADA) target HbA1c of <7.0% (66.1% with semaglutide vs 45.1% with canagliflozin, odds ratio [OR] 2.77, p<0.0001).
- For the stricter target of ≤6.5%, semaglutide also outperformed canagliflozin (52.8% vs 23.6%, OR 4.19, p<0.0001).
Secondary Measure (Body Weight):
- Semaglutide demonstrated greater mean weight reduction from baseline (-5.3 kg) compared to canagliflozin (-4.2 kg), with an ETD of -1.06 kg (95% CI: -1.76 to -0.36, p=0.0029).
- A larger proportion of patients achieved ≥10% weight loss with semaglutide (22.3%) compared to canagliflozin (8.9%), with an OR of 2.99 (p<0.0001).
- Post hoc analysis showed semaglutide also led to significant reductions in total cholesterol, LDL cholesterol, and triglycerides, which are important for cardiovascular risk reduction.
Safety Profile:
- Gastrointestinal adverse events were significantly more common with semaglutide (46.9% vs 27.9%), with nausea and diarrhoea as the most frequent issues.
- Canagliflozin showed higher rates of genitourinary infections (12.2% vs 2.6%).
- Severe or symptomatic hypoglycaemia was rare and comparable between the groups (1.5% vs 1.3%).
- Treatment discontinuation due to adverse events occurred more frequently with semaglutide (9.7%) compared to canagliflozin (5.1%).
Considerations:
The study population may not fully reflect the diversity of real-world patients with type 2 diabetes. Gastrointestinal tolerability with semaglutide limits its applicability in some patients. Further research could evaluate long-term cardiovascular and renal outcomes.
Reference:
Lingvay, I., et al. (2019). The Lancet Diabetes & Endocrinology, 7(11), 834-844. doi:10.1016/S2213-8587(19)30311-0 .
Disclosure:
This review was prepared with assistance from AI-based summarisation tools and expert input to ensure clarity and accuracy.
