In patients with inadequately controlled type 2 diabetes on SGLT-2 inhibitors, adding semaglutide significantly improved HbA1c and reduced body weight compared to placebo, though it was associated with an increased frequency of gastrointestinal side effects.
PICO Summary
Population:
Adults (N=302) with type 2 diabetes and HbA1c levels between 7.0%–10.0%, on stable SGLT-2 inhibitor therapy for at least 90 days.
Intervention:
Subcutaneous semaglutide 1.0 mg, administered weekly for 30 weeks after a structured dose-escalation phase (0.25 mg for 4 weeks, followed by 0.5 mg for another 4 weeks).
Comparison:
Placebo (volume-matched), with both groups maintaining their background SGLT-2 inhibitor therapy.
Outcome:
- Efficacy: Significant reduction in HbA1c levels in the semaglutide group compared to placebo (−1.42% estimated treatment difference; p<0.0001), as well as substantial body weight reduction (−3.81 kg difference; p<0.0001).
- Safety and Tolerability: Gastrointestinal side effects, notably nausea, vomiting, and diarrhoea, were more frequent with semaglutide (37.3% vs. 13.2% in placebo). Serious adverse events were comparable across groups, though 4.3% of semaglutide patients discontinued due to side effects.
Clinical Summary
Main Finding:
The addition of semaglutide to existing SGLT-2 inhibitor therapy achieved marked improvements in glycaemic control and weight reduction over 30 weeks. In the semaglutide group, mean HbA1c dropped by 1.42% more than the placebo group (from a mean baseline of 8.1%), bringing many patients closer to target levels. Furthermore, semaglutide led to an average body weight decrease of 3.81 kg versus placebo. These changes underscore the additive metabolic benefits of semaglutide in combination therapy, making it a potent choice for patients not meeting glycaemic targets on SGLT-2 inhibitors alone.
Clinical Relevance:
These results are particularly relevant for individuals with type 2 diabetes who, despite SGLT-2 inhibitor therapy, remain above HbA1c and weight goals. The study’s dual outcomes—improvement in both glucose control and weight loss—address common challenges in managing diabetes-related metabolic risks. However, gastrointestinal side effects, particularly nausea (reported by 37.3% in the semaglutide group), may impact adherence. The dose-escalation schedule appears to help some patients acclimate, yet approximately 4.3% discontinued due to adverse effects, indicating the importance of monitoring for tolerance.
Semaglutide’s effects in reducing HbA1c and body weight in the SUSTAIN 9 study align with previous findings of GLP-1 receptor agonists. These outcomes reinforce its position as a valuable adjunct therapy for patients who prefer once-weekly dosing and could benefit from the enhanced metabolic control it offers, despite minor tolerability concerns.
Study Overview:
- Type of Study: Randomised, double-blind, placebo-controlled, parallel-group trial (SUSTAIN 9).
- Sample Size & Population: 302 adults with inadequately controlled type 2 diabetes on SGLT-2 inhibitors.
- Intervention Duration & Doses: 30-week treatment period with semaglutide, following an 8-week dose escalation to a maintenance dose of 1.0 mg weekly.
- Comparison: Placebo, maintaining baseline SGLT-2 inhibitor therapy.
Outcomes:
- Primary Measure (HbA1c): Semaglutide achieved a −1.42% greater reduction in HbA1c compared to placebo (p<0.0001).
- Secondary Measure (Body Weight): Mean weight reduction in the semaglutide group exceeded placebo by 3.81 kg, demonstrating significant weight management benefits.
- Safety Profile: Gastrointestinal side effects, including nausea, were the most frequent adverse events, contributing to a higher discontinuation rate in the semaglutide group.
Considerations:
While semaglutide shows promise as an add-on to SGLT-2 inhibitors for metabolic control, the high incidence of gastrointestinal effects suggests a need for careful patient selection and monitoring, especially during dose escalation.
Reference:
Zinman, B., Bhosekar, V., Busch, R., et al. (2019). The Lancet Diabetes & Endocrinology, 7(5), 356–367. doi:10.1016/S2213-8587(19)30066-X
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.
