Pre-emptive Insulin to Prevent High Glucose After a Knee Steroid Injection in Adults With Type 2 Diabetes

Intra-articular corticosteroid injections can produce clinically important but transient hyperglycaemia in people with type 2 diabetes. Published studies have largely characterised this glucose response rather than testing a standardised strategy to prevent it.

PREVENT-SIH is a phase 2, randomised, parallel-group trial in adults with type 2 diabetes managed without insulin or insulin secretagogues. All participants will receive a clinically indicated, standardised intra-articular injection of triamcinolone acetonide crystalline suspension 40 mg into one index knee for symptomatic knee osteoarthritis.

Participants will be randomly assigned 1:1 to a pre-emptive NPH insulin pathway or usual reactive diabetes management. The pre-emptive pathway comprises three weight-based NPH doses starting immediately after the corticosteroid injection, with prespecified glucose-based dose modification, withholding and discontinuation rules. Both groups will continue stable background diabetes medication and will receive identical blinded continuous glucose monitoring, capillary glucose monitoring, safety instructions, scheduled contacts and rescue thresholds.

Continuous glucose monitoring data will be collected for a 72-hour baseline period and for at least 96 hours after injection. The primary analysis will compare the percentage of valid readings above 180 mg/dL during the first 72 hours after injection, adjusted for baseline continuous glucose monitoring time above 180 mg/dL, site and HbA1c stratum. Rescue treatment and other post-randomisation diabetes treatment changes will be retained in the primary treatment-policy analysis.

Inclusion criteria

• Age 40 to 80 years at consent.
• Documented diagnosis of type 2 diabetes for at least 6 months.
• HbA1c from 6.5% through 9.0% measured within 30 days before randomisation.
• Symptomatic osteoarthritis of one knee for which the treating clinician has independently determined that an intra-articular corticosteroid injection is clinically indicated.
• Planned administration of one intra-articular injection of triamcinolone acetonide crystalline suspension 40 mg into the index knee.
• Diabetes managed without insulin, sulfonylureas or meglitinides.
• Permitted glucose-lowering medications at stable doses for at least 30 days before randomisation.
• Estimated glomerular filtration rate at least 45 mL/min/1.73 m² within 60 days before randomisation.
• Capillary glucose from 90 through 250 mg/dL immediately before the injection.
• Ability and willingness to perform scheduled capillary glucose testing, administer or receive subcutaneous insulin if assigned, follow hypoglycaemia instructions and remain contactable through day 7.
• Ability to wear the study continuous glucose monitoring device and provide informed consent.

Exclusion criteria

• Type 1 diabetes, latent autoimmune diabetes in adults, pancreatogenic diabetes or another specific diabetes type requiring insulin.
• Current basal, prandial, premixed or pump insulin treatment.
• Current sulfonylurea or meglitinide treatment.
• HbA1c below 6.5% or above 9.0%.
• Capillary glucose below 90 mg/dL or above 250 mg/dL immediately before injection.
• Fasting glucose above 250 mg/dL, random glucose above 300 mg/dL, clinically significant ketonaemia or hyperglycaemia requiring immediate treatment during screening.
• Estimated glomerular filtration rate below 45 mL/min/1.73 m².
• Severe hepatic impairment or another condition expected to materially alter insulin clearance or hypoglycaemia risk.
• Level 3 hypoglycaemia requiring third-party assistance during the previous 6 months.
• Documented impaired awareness of hypoglycaemia.
• Pregnancy, planned pregnancy during study participation or breastfeeding.
• Oral, intravenous or intramuscular corticosteroid use within 30 days before the study injection.
• Any intra-articular, epidural, periarticular or soft-tissue corticosteroid injection within 30 days before the study injection.
• Planned additional systemic or injected corticosteroid exposure before the day-7 assessment.
• Acute febrile illness, active systemic infection or acute deterioration in health at screening or injection.
• Suspected septic arthritis, infection over the injection site, prosthetic index knee, uncontrolled bleeding disorder or another contraindication to knee injection.
• Known allergy or clinically significant hypersensitivity to triamcinolone acetonide, human NPH insulin, insulin aspart, protamine, lidocaine or required excipients.
• Known allergy to continuous glucose monitoring adhesive or a skin condition preventing sensor use.
• Cognitive, visual, physical or social limitation that would prevent safe glucose testing, insulin administration, hypoglycaemia treatment or study contact.
• Participation in another interventional study likely to affect glucose or corticosteroid response.
• Any condition that, in the investigator's documented judgement, makes participation unsafe for a reason not otherwise captured above.