In patients with type 2 diabetes treated with metformin and basal insulin, once-weekly semaglutide significantly improved glycaemic control (HbA1c reduction) and body weight compared to thrice-daily insulin aspart, though it was associated with higher rates of gastrointestinal side effects.
PICO Summary
Population:
Adults with type 2 diabetes inadequately controlled with basal insulin (glargine) and metformin, HbA1c between 7.5%-10.0%.
Intervention:
Once-weekly semaglutide (1.0 mg subcutaneously).
Comparison:
Thrice-daily insulin aspart (dose adjusted based on self-monitored glucose profiles).
Outcome:
Efficacy:
Semaglutide achieved greater HbA1c reduction (mean decrease of 1.5%) compared to insulin aspart (1.2%), with significant weight loss (-4.1 kg vs. +2.8 kg; p<0.001).
Safety and Tolerability:
Gastrointestinal adverse events (nausea, diarrhoea) were more common with semaglutide (58.5% vs. 52.1%), leading to higher discontinuation rates.
Clinical Summary
Main Finding:
Once-weekly semaglutide demonstrated superior glycaemic control and significant weight loss compared to thrice-daily insulin aspart in patients with type 2 diabetes on metformin and basal insulin. Hypoglycaemia incidence was low and comparable between groups.
Clinical Relevance:
The results suggest semaglutide offers a less burdensome regimen with improved weight outcomes, supporting its use as an alternative to intensify therapy in patients with type 2 diabetes. The convenience of weekly dosing may improve adherence, but gastrointestinal tolerability should be considered during patient selection.
Study Overview:
- Type of Study: Randomised, open-label, phase 3b trial.
- Sample Size & Population: 1,748 participants across 21 countries.
- Intervention Duration & Doses: 52 weeks; semaglutide (1.0 mg weekly) versus insulin aspart (thrice daily, dose titrated).
- Comparison: Basal insulin glargine with either semaglutide or insulin aspart.
Outcomes:
Primary Measure: Glycaemic Control (HbA1c Reduction)
- Semaglutide led to a mean reduction in HbA1c of 1.5% (16.6 mmol/mol) from a baseline of 8.6%.
- Insulin aspart achieved a mean reduction in HbA1c of 1.2% (13.4 mmol/mol).
- The estimated treatment difference (ETD) was -0.29% (95% confidence interval [CI] -0.38 to -0.20; p < 0.0001), confirming non-inferiority of semaglutide to insulin aspart.
- Greater proportions of patients treated with semaglutide reached glycaemic targets:
- HbA1c ≤7.5% (74.7% vs. 65.1%, odds ratio [OR] 1.68; p < 0.0001).
- HbA1c <7.0% (40.4% vs. 30.2%, OR 2.90; p < 0.0001).
- HbA1c ≤6.5% (36.6% vs. 22.9%, OR 11.06; p < 0.0001).
Secondary Measure: Weight Changes
- Semaglutide treatment resulted in weight loss of -4.1 kg from a baseline of 87.9 kg.
- Insulin aspart was associated with weight gain of +2.8 kg over the same period.
- The ETD for weight change was -6.99 kg (95% CI -7.41 to -6.57; p < 0.001).
- Semaglutide significantly improved other weight-related outcomes:
- Proportions achieving ≥5% weight loss: 24.15 OR (95% CI 15.90 to 36.68; p < 0.001).
- Proportions achieving ≥10% weight loss: 35.98 OR (95% CI 13.25 to 97.71; p < 0.001).
- Reduction in BMI: -2.54 kg/m² (95% CI -2.69 to -2.39).
- Reduction in waist circumference: -5.31 cm (95% CI -5.81 to -4.80).
Safety Profile: Hypoglycaemia
- Rates of severe hypoglycaemia were low in both groups:
- Semaglutide: 0.5% of participants, with 4 events reported.
- Insulin aspart: 0.7%, with 7 events reported.
- Non-severe hypoglycaemia was significantly less frequent with semaglutide:
- Clinically significant hypoglycaemia (blood glucose <3.0 mmol/L): 15.9% with semaglutide vs. 43.4% with insulin aspart (p < 0.0001).
- Symptomatic hypoglycaemia (BG <3.9 mmol/L): 37.8% vs. 60.4% (p < 0.0001).
Other Outcomes: Blood Pressure and Lipids
Blood Pressure:
- Systolic BP decreased by -3.0 mmHg with semaglutide and increased by +0.9 mmHg with insulin aspart (ETD -3.9 mmHg, p < 0.0001).
- Diastolic BP also decreased significantly with semaglutide (p = 0.0216).
Lipids:
- Changes were minimal and not statistically significant, except for a reduction in total cholesterol favouring semaglutide (p < 0.05).
Quality of Life (QoL) and Treatment Satisfaction
- Patient-reported outcomes indicated higher satisfaction with semaglutide:
- Semaglutide improved scores across multiple domains of the Diabetes Quality of Life Clinical Trial Questionnaire (DQLCTQ-R) and Treatment Related Impact Measure for Diabetes (TRIM-D) compared to insulin aspart.
- Fewer injections (weekly vs. thrice-daily) likely contributed to enhanced adherence and patient-reported outcomes.
Adverse Events (AEs)
Common AEs:
- Gastrointestinal symptoms, including nausea (14.8%), diarrhoea (7.4%), and vomiting (5.7%), were more frequent with semaglutide compared to insulin aspart (0.8%, 2.7%, and 0.6%, respectively).
Serious AEs:
- Similar rates of serious adverse events between groups (7.4% semaglutide vs. 9.7% insulin aspart).
- Higher rates of treatment discontinuation in the semaglutide group (3.7% vs. 0.7%), driven mainly by gastrointestinal side effects.
Key Summary of Findings:
Semaglutide provides superior efficacy in glycaemic control and weight management with a lower risk of hypoglycaemia compared to insulin aspart. Its once-weekly administration offers a more convenient treatment option for patients, though gastrointestinal tolerability remains a challenge for some. These results highlight semaglutide as a valuable addition to the therapeutic armamentarium for managing type 2 diabetes.
Considerations:
The trial demonstrated significant benefits of semaglutide in glycaemic control and weight management, but the higher rates of gastrointestinal side effects may impact patient acceptability. Long-term studies are needed to evaluate sustained safety and cardiovascular outcomes.
Reference:
Kellerer, M., et al. (2022). Diabetes, Obesity and Metabolism, 24(12), 1788-1799. doi:10.1111/dom.14765
Disclosure:
This summary was created using AI-assisted tools and reviewed for clinical accuracy.