Short Summary
- In patients with type 2 diabetes on diet and exercise or metformin, oral semaglutide significantly improved glycemic control (HbA1c reduction) and weight loss in a dose-dependent manner compared to placebo, with similar efficacy to subcutaneous semaglutide, though it was associated with higher rates of gastrointestinal side effects.
PICO Summary
Population:
- Adults (N=632) aged ≥18 years with type 2 diabetes, HbA1c levels between 7.0%-9.5%, BMI 25-40, receiving diet and exercise or stable metformin.
Intervention:
- Oral semaglutide, once daily, with dosages of 2.5 mg, 5 mg, 10 mg, 20 mg, and 40 mg (dose escalated every 2, 4, or 8 weeks depending on regimen).
Comparison:
- Placebo (oral, double-blind) and subcutaneous semaglutide (1 mg weekly).
Outcome:
- Efficacy: At 26 weeks, significant HbA1c reduction for all doses of oral semaglutide compared to placebo (P < .001) with comparable efficacy to subcutaneous semaglutide in the 20 mg and 40 mg groups. Weight loss was also significantly greater with oral semaglutide compared to placebo in doses ≥10 mg (P < .001).
- Safety and Tolerability: Adverse events, primarily mild-to-moderate gastrointestinal, were common in oral semaglutide groups (63%-86%) versus placebo (68%), with dose-related discontinuation rates due to side effects, mainly gastrointestinal.
Clinical Summary
Main Finding:
- Oral semaglutide significantly improves HbA1c and body weight in a dose-dependent manner, offering a new non-injectable option for managing type 2 diabetes.
Clinical Relevance:
- This study provides evidence supporting oral semaglutide as an effective and convenient alternative for patients who prefer not to use injectable treatments, particularly given its efficacy in achieving glycaemic targets. Gastrointestinal tolerability remains a limitation for some patients.
Study Overview:
- Type of Study: Phase 2, randomised, parallel-group, dosage-finding clinical trial.
- Sample Size & Population: 632 patients with type 2 diabetes.
- Intervention Duration & Doses: 26-week treatment period with once-daily oral semaglutide in doses of 2.5 mg to 40 mg, compared with once-weekly subcutaneous semaglutide (1 mg).
- Comparison: Oral placebo, double-blind.
Outcomes:
- Primary Measure (HbA1c): Significant HbA1c reductions across all doses of oral semaglutide, with a mean reduction of up to 1.9% for the highest doses versus 0.3% in the placebo group.
- Secondary Measure (Body Weight): Weight loss also achieved with oral semaglutide (up to −6.9 kg for higher doses vs. −1.2 kg with placebo).
- Safety Profile: Higher prevalence of gastrointestinal events in semaglutide groups (up to 77%), with a dose-dependent increase in discontinuations due to adverse events.
Considerations:
- The high frequency of gastrointestinal side effects limits generalisation; further phase 3 studies are warranted for long-term efficacy and safety evaluation.
Reference: Davies, M., et al. (2017). JAMA, 318(15), 1460-1470. doi:10.1001/jama.2017.14752
Disclosure: This article on Hormone Insight was created with both human and AI assistance. The human expert editor reviewed the article before publication to ensure accuracy, quality, and clarity.
