Effect of engineered mesoporous silica particles with tailored pore size on glycaemic control in individuals with prediabetes or type 2 diabetes: a randomised, double-blind, placebo-controlled SHINE trial

Background Prediabetes is a major global health concern due to its high prevalence and strong association with obesity and increased cardiovascular risk. Most individuals with prediabetes progress to type 2 diabetes, and although lifestyle modification is recommended early, long-term adherence and scalability remain challenging. SiPore21 offers a promising solution. SiPore21 is an oral gel containing engineered mesoporous silica particles that act locally in the gut by entrapping digestive enzymes and modulating macronutrient uptake. Methods This 12-week, randomised, double-blind, placebo-controlled, multicentre trial was conducted at 27 centres across three European countries (ClinicalTrials.gov: NCT06087822). During Oct 5, 2023 and Jul 30, 2024, 318 participants were enrolled and assessed, and 312 completed the intervention (SiPore21 n=155; placebo n=157). Adults aged 18–70 years with overweight or obesity (BMI > 25 to ≤40 kg/m 2 ) and elevated HbA1c (≥42 and ≤58 mmol/mol [≥6 and ≤ 7.5%]) were eligible. Participants were randomly assigned 1:1 to SiPore21 or placebo using a web-based interactive randomisation system. SiPore21 was administered three times daily with meals for 12 weeks. The primary outcome was change in HbA1c from baseline to Week 12. Secondary outcomes included changes in body weight, lipid profiles, and other metabolic parameters. Safety and tolerability were assessed throughout. The primary analysis was performed on all participants who received at least one dose and at least one post-baseline HbA1c measurement; the safety analysis included all participants who received at least one dose. Findings SiPore21 significantly reduced HbA1c from baseline (p = 0.0036), indicating a favourable glycaemic effect, whereas no significant reduction was observed with placebo (p = 0.0872). In a post hoc sex-stratified analysis, the HbA1c reduction vs. placebo was statistically significant in women (p = 0.019), whereas a marked placebo response in men attenuated the overall between-group difference. SiPore21 also improved body weight (p = 0.0374), fat mass (p = 0.05), and lipid measures (LDL-C; p=0.035, total cholesterol; p=0.0496) compared to placebo, and was associated with reduced progression from prediabetes to diabetes (p = 0.0233) and increased reversion to earlier glycaemic states (p = 0.0044). SiPore21 was safe and well tolerated, with only mild, transient gastrointestinal events and no serious adverse device effects. Interpretation SiPore21 improved glycaemic control, body composition, and lipid metabolism while stabilising glycaemic status, whereas corresponding improvements were not observed in the placebo group. SiPore21 was well tolerated, with no clinically meaningful safety concerns identified. These findings support its potential as a safe and effective non-pharmacological option for prediabetes or early type 2 diabetes. Funding Sigrid Therapeutics AB.