In a 24-week trial with participants living with overweight or obesity, a 2.24g intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo, researchers from China report.
The intragastric expandable capsules consists of two naturally derived components, food-grade carboxymethylcellulose cross-linked with citric acid, forming a three-dimensional polymer matrix that rapidly absorbs water and occupies the volume of the stomach and small intestine when administered orally with water before a meal, subsequently producing satiety.
The researchers explain that “each capsule contains no less than 10,000 highly absorbent cellulose-based hydrogel particles, with each capsule weighing 5.6 g. It is recommended that people living with overweight and obesity individuals are recommended to take four capsules orally with 500ml water 30 min before lunch and dinner. After the capsule shell dissolves in the acidic fluid of the stomach, the food-grade hydrogel shows an osmotic gradient that drives water to fill the gaps between the polymer chains and expands to 200 ml, occupying approximately one-quarter of the average stomach volume; thus, daily food consumption is reduced. The expended gel particles are sensitive to pH, which enables them to degrade in the colon, releasing water to be reabsorbed; the hydrogel is then expelled through defecation.”
This phase 3, randomised, double-blind, placebo-controlled, multi-centre superiority study was designed to evaluate the efficacy and safety of 2.24g oral intragastric expandable capsules twice daily versus placebo for body weight management. Conducted at six hospitals in China, eligible participants were 18-60 years old and had a body mass index of at least 24kg/m2. Participants were randomly allocated to the 2.24g intragastric expandable capsule group or placebo (1:1) group.
Body weight, height, waist circumference and vital signs (systolic and diastolic blood pressure and heart rate) were measured at baseline and were repeated at weeks 4, 12 and 24 (within 14 days on either side of the scheduled visit day) except for height. Physical examinations were conducted at baseline and week 24, including assessments of general appearance, the thyroid gland, and the respiratory, cardiovascular, abdomen and nervous systems. The EuroQol five-dimensional questionnaire (EQ-5D) for the assessment of quality of life was completed, and adverse events were recorded at each visit.
Primary outcomes were the percentage of weight loss of at least 5% of baseline body weight, which was referred to as the weight loss response rate, and the percentage change in body weight from baseline to week 24 (2.24 g intragastric expandable capsules vs. placebo). Secondary outcomes (2.24 g intragastric expandable capsules vs. placebo) included the percentage change in body weight from baseline to week 12, the change in waist circumference from baseline to week 12 or week 24, the lipid profile (triglyceride, total cholesterol, low-density lipoprotein cholesterol), fasting plasma glucose levels, fasting insulin levels, glycated haemoglobin levels and EQ-5D score.
Outcomes
In total, 280 were enrolled and randomised to the intragastric expandable capsule (n=142) and placebo groups (n=138) with demographics and baseline characteristics comparable between the two groups. The mean age was 33 years and 58.8% were female. The mean body weight was 81.8kg, mean body mass index was 29.4kg/m2 and mean waist circumference was 95.8 cm.
The mean body weight change at week 24 was −4.9% ± 5.4% (SE 0.4) with intragastric expandable capsules versus −1.9% ± 4.0% (SE 0.4) with placebo (coprimary endpoint; estimated treatment difference −3.0%, 95% CI −4.1 to −1.9, p<0.001) using the full analysis set. The mean body weight change at week 24 was −6.1% ± 5.4% (SE 0.4) with intragastric expandable capsules versus −2.5% ± 4.5% (SE 0.4) with placebo (estimated treatment difference −3.6%, 95% CI −5.0 to −2.3, p<0.001) using the per protocol set.
Body weight decreased without statistical significance in the intragastric expandable capsule group compared with the placebo group at week 12 (−3.5% vs. −2.8%, p=0.141), but the weight reduction superiority became significant at week 24. In the per protocol set, body weight loss was significantly lower in the intragastric expandable capsule group than in the placebo group at week 12 (−3.8% vs. −2.6%, p=0.020), and the superiority remained significant at week 24. No weight loss plateau was observed during the 24-week follow-up period and weight loss was sustained in the per protocol set during the trial.
The weight loss response rate (weight reduction exceeding 5% of baseline weight) was 45.0% with intragastric expandable capsules versus 19.7% with placebo (coprimary endpoint; estimated treatment difference 25.3%, 95% CI 14.7% to 35.9%, p<0.001) using the full analysis set and 55.9% versus 26.2%, respectively, using the per protocol set (estimated treatment difference 29.6%, 95% CI 17.1% to 42.2%, p<0.001), indicating superiority of the capsules to placebo for weight loss.
Additional outcomes showed that:
Mean body weight change at week 12 was −3.8% ± 3.7% with intragastric expandable capsules versus −2.6% ± 3.3% with placebo (p=0.020)
Benefits significantly favouring intragastric expandable capsules versus placebo were discovered for waist circumference (intragastric expandable capsules vs. placebo, −5.6 ± 8.3 cm vs. −2.9 ± 4.8 cm, p = .003) and BMI (intragastric expandable capsules vs. placebo, −1.7 ± 1.6 kg/m2 vs. −0.7 ± 1.3 kg/m2, p ≤ .001) at week 24
The proportion of patients with a weight reduction exceeding 10% of the baseline weight was 17.1% with intragastric expandable capsules versus 4.4% with placebo (estimated treatment difference 12.8%, 95% CI 5.6%-16.9%, p=0.001) using the full analysis set and 21.6% versus 5.8%, respectively, using the per protocol set (estimated treatment difference 15.8%, 95% CI 0.7%-24.7%, p=0.001)
Fasting insulin levels at week 24 decreased significantly in the intragastric expandable capsule group compared with the placebo group (intragastric expandable capsules vs. placebo, −3.25 ± 15.38 μIU/ml vs. 0.24 ± 7.87 μIU/ml, p=0.008)
Blood pressure at week 24 significantly decreased in the intragastric expandable capsule group compared with the placebo group (114.8/77.7 mmHg vs. 118.7/79.9 mmHg, p=0.017), but the significance was reduced when the change from baseline to week 24 was compared between the two groups (p=0.611). The improvements in the lipid profile, fasting plasma glucose levels, heart rate and EQ-5D scores were not significantly different between the active product and placebo groups.
The proportion of participants reporting adverse events was 117 (83.6%) of 140 participants in the intragastric expandable capsule group and 118 (86.1%) of 137 participants in the placebo group, with no significant difference between the two groups (p=0.617). The most frequently reported adverse events possibly associated with the product were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), including diarrhoea, abdominal pain and abdominal distention, which were mostly transient and mild in severity.
The findings were reported in the paper, ‘Efficacy and safety of intragastric expandable oral capsules in adults with overweight or obesity: A randomized, double-blind, placebo-controlled trial’, published in Diabetes, Obesity and Metabolism. To access this paper, please click here