The study aims to investigate effects of inhibiting glucocorticoid activation on skin function and wound healing in patients with type 2 diabetes. Half of patients will be given a drug to inhibit glucocorticoid activation and the other half will be given a placebo.

Glucocorticoids are known to impair skin function and wound healing which are also compromised in patients with type 2 diabetes. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates glucocorticoids in target tissues including skin. Pre-clinical data demonstrate that 11β-HSD1 inhibition improves skin function and wound healing but this has not been investigated in man.

Using the 11β-HSD1 inhibitor AZD4017, we will investigate if

1. Oral AZD4017 inhibits 11β-HSD1 activity in skin
2. AZD4017 is safe and well-tolerated in patient with T2DM
3. Oral AZD4017 regulates skin function
4. Systemic glucocorticoid levels and skin 11β-HSD1 activity, independently or in combination correlate with measures of skin function

Study feasibility will also be assessed; if successful, data from this pilot study will inform power calculations for a future trial to investigate the ability of 11β-HSD1 inhibition to promote foot ulcer healing in type 2 diabetes.

Inclusion Criteria:

1. Able and willing to consent
2. Type 2 diabetes with HbA1c ≤11% (≤97 mmol/mol) at screening while taking standard therapy at a stable dose for ≥10 weeks

Exclusion Criteria:

1. Women of child-bearing potential
2. Active leg/foot ulceration
3. Clinically relevant acute electrocardiogram anomalies
4. Uncontrolled hypertension
5. Endocrine disorder (other than type 2 diabetes ), including type 1 or secondary diabetes (except treated hypothyroidism)
6. Gilbert's disease
7. Alanine aminotransferase and/or aspartate aminotransferase and/or alkaline phosphatase >1.5x upper limit of normal (ULN)
8. Bilirubin >1.5x ULN
9. Estimated glomerular filtration rate <45 ml/min/m2
10. Creatine kinase >2x ULN
11. Drug abuse within the last year
12. Any glucocorticoid treatment within 3 months of screening
13. Anti-coagulant medication
14. Probenecid therapy
15. Medical/surgical procedure or trauma during drug administration or one week after drug cessation (excluding skin biopsies)
16. Involvement in trial planning and/or conduct
17. Participation in other clinical study within 1 month
18. Deemed inappropriate to participate by the trial team

Treatment groups will be allocated in a double-blind manner. Participants will be blinded to the treatment they receive (placebo or drug) throughout all stages of the study. Investigators will also be blinded to the treatment until all samples have been collected and processed. Blinding will be generated by a dedicated trials pharmacy representative who is not otherwise associated with this study.