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

SiPore21 is an oral gel containing engineered mesoporous silica particles. These particles are micron-sized and tailored to have pores with a specific diameter, which are slightly larger than the size of digestive enzymes but smaller than undigested food. Owing to this unique physical structure and the consequent diffusion of enzymes into the pores, SiPore21 functions as a molecular sieve that physically separates digestive enzymes from undigested or partially digested food in the gastrointestinal tract. This physical separation reduces the enzymatic breakdown of carbohydrates and fats, thereby lowering nutrient absorption.1,2 Consistent with this mode of action, mesoporous silica particles with precisely engineered pore sizes have demonstrated selective enzyme sequestration in vitro, ex vivo, and in vivo settings, resulting in reduced carbohydrate and lipid digestion. These positive effects were pore size-dependent and were not observed in particles with pores smaller than the enzymes, supporting a size-selective mode of action rather than non-specific adsorption.2 The downstream biological effects of this mode of action have been demonstrated in several preclinical and clinical studies using SiPore21 prototypes. In diet-induced obese mice, SiPore21 prototype treatment significantly reduced body weight and fat composition, suppressed further weight gain, and improved glucose tolerance.3,4 In the first-in-human trial, 12 weeks of treatment was safe and significantly lowered HbA1c and low-density lipoprotein cholesterol in individuals with obesity.2,5 A subsequent proof-of-concept study confirmed these findings in individuals with prediabetes and early type 2 diabetes (T2D), showing clinically meaningful HbA1c reductions and improvements in several metabolic parameters with minimal adverse effects.6

These findings demonstrate the safety and metabolic benefits of SiPore21 prototypes and underscore the potential of SiPore21 as a novel, non-pharmacological approach to address one of today’s most pressing metabolic health challenges, the prevention and early management of T2D. Prediabetes, or intermediate hyperglycaemia, is characterised by blood glucose above normal but below the diagnostic threshold for T2D. It represents a major global health concern due to its high prevalence and strong association with obesity, insulin resistance, and increased cardiovascular risk.7 Approximately 25% of individuals with prediabetes progress to T2D within three to five years, and up to 70% will do so over their lifetime.8 Despite its clinical importance, management options remain limited.

Current guidelines for prediabetes primarily recommend lifestyle interventions, such as dietary modification and increased physical activity. Similarly, for early T2D, promoting lifestyle change remains the foundation of disease management before pharmacological therapy is initiated.7,9 However, these strategies are resource-intensive, challenging to implement in real-world settings, and often associated with poor long-term adherence.10,11 Pharmacological options are also limited: while metformin is sometimes prescribed to individuals at high risk of developing T2D, its broader use in prediabetes is constrained by tolerability issues and the absence of a formal indication.12,13

Given these challenges, there is a pressing need for safe, effective, and scalable non-pharmacological strategies to prevent disease progression and support metabolic health. In this context, SiPore21 represents a novel, locally acting intervention that acts within the gastrointestinal tract without systemic exposure, offering a potential adjunct or complementary approach to existing lifestyle-based strategies. The present clinical study, SHINE (SiPore Halts Intermediate Hyperglycaemia), was therefore designed to evaluate the safety and efficacy of SiPore21 in individuals with overweight or obesity, diagnosed with prediabetes or early T2D.