MASTERMIND - Understanding Individual Variation in Treatment Response in Type 2 Diabetes

Participants will withdraw sulphonylurea therapy for up to 2 weeks (part 1) followed by an optional cross-over extension (part 2)where they are randomized to 4 weeks of treatment with Gliclazide (DPP-IV thera) or Sitagliptin (sulphonylurea), followed by 4 weeks of the second treatment with a 2 week wash-out period in between.

Part 1 will allow assessment of response rates to long standing sulphonylurea treatment in clinical practice and potential predictors of this, as well as whether a very brief period (1 week) of treatment withdrawal is a valid assessment of an individual's response to therapy. Part 2 will allow comparison of the approach in part one with response to the same treatment in a trial setting and will allow assessment on whether response is consistent across therapies with different mechanisms of action.

Inclusion criteria

• Age >18 and <80
• Clinical diagnosis of Type 2 Diabetes
• Currently treated with sulphonylurea tablets
• No change in diabetes treatment (new treatments or dose change) within last 3 months
• Last HbA1c (taken within last 12 months) of ≥42 mmol/mol and ≤75 mmol/mol (6-9%)
• Able and willing to monitor home blood glucose
• Able and willing to give informed consent

Exclusion criteria

• Current treatment includes: insulin, GLP-1 agonists, DPP-IV inhibitors, glinides
• Renal impairment (eGFR <30 ml/min/1.73m2)
• Active infection (any infection requiring antibiotics at present)
• Recent (within 3 months) surgery or planned surgery
• Cardiovascular disease (angina, myocardial infarction, stroke, transient ischemic episode) occurring within the previous 3 months
• Previous history of pancreatitis
• Pregnant, breastfeeding or planning a pregnancy over the study period
• Unable/unwilling to monitor home blood glucose