Response To Oral Agents in Diabetes (ROAD)- Pilot Study
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Gliclazide MR; Sitagliptin; Pioglitazone; Metformin
Intervention description: 30mg daily increased to 60mg if HbA1c > 7% at 3 months; Sitagliptin 100mg daily for 6 months; Pioglitazone 30mg daily , increased to 45mg daily if HbA1c >7% at 3 months. 6 months duration; Metformin 500 mg od for 1 week, bd for 1 week, 1g mane 500 mg nocte 1 week, 1g bd there after. Total of 6 months treatment
Intervention MeSH terms: Metformin; Pioglitazone; Sitagliptin Phosphate; Gliclazide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 36 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Diabetes therapies; Pharmacogenetics

Summary:

      This proposal is to fund a pilot study to assess feasibility and refine methodology for an
      intended large Scotland wide study on Response to Oral Agents in Diabetes (ROAD). The study
      will collect cohorts of patients who have carefully controlled standardised dose titration
      and monitoring with an assessment of drug response and side effects over a 6 month period.
      The primary aim will be to use these cohorts to investigate phenotypic and genotypic
      (pharmacogenetic) determinants of response.

      Drug naïve patients will be treated with Metformin. Patients who have failed on Metformin or
      are intolerant of Metformin will be randomised to gliclazide, pioglitazone or sitagliptin.
      With the ability to capture patient data beyond 6 months via data linkage we will monitor
      time to treatment failure and therefore compare which of the 3 oral agents is the best
      therapy to use after Metformin in a cost efficient and "real world" RCT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cohort 1 - metformin treatment

               -  Type 2 diabetes diagnosed more than 6 weeks prior to visit 1

               -  GP considers adequate diet and lifestyle advice given

               -  Age >35 and < 80

               -  Age of diabetes diagnosis >35

               -  White European

               -  HbA1c >7% & <=9%

               -  eGFR>=50 ml/min

               -  ALT <= 2.5*ULN

               -  Contactable by telephone

          -  Cohort 2 - 2nd line treatment

               -  Type 2 diabetes

               -  Treated with metformin for more than 3 months; or metformin intolerant

               -  Age >35 and < 80

               -  Age of diabetes diagnosis >35

               -  White European

               -  HbA1c >7% & <=9%

               -  eGFR>=50 ml/min

               -  ALT <= 2.5*ULN

               -  No previous history of heart failure; No patients with documented evidence of
                  left ventricular systolic dysfunction OR with symptoms and signs consistent with
                  a clinical diagnosis of heart failure

               -  No treatment with Gemfibrozil or Rifampicin (CYP2C8 inhibitor or inducer
                  respectively); or with Miconazole or phenylbutazone (increased hypoglycemic
                  effect of gliclazide).

               -  No diagnosis of osteoporosis

               -  Contactable by telephone

        Exclusion Criteria:

          -  Cohort 1

               -  Type 1 diabetes

               -  HbA1c >9% or <=7%

               -  eGFR<50 ml/min

               -  ALT > 2.5*ULN

               -  Alcohol consumption in excess of 50 units per week

               -  Pregnancy, lactation or a female planning to conceive within the study period

               -  Any other significant medical reason for exclusion as determined by the
                  investigator

          -  Cohort 2

               -  Type 1 diabetes

               -  HbA1c >9% or <=7%

               -  eGFR< 50 ml/min

               -  ALT > 2.5*ULN

               -  Previous history of heart failure OR documented evidence of left ventricular
                  systolic dysfunction OR symptoms and signs consistent with a clinical diagnosis
                  of heart failure

               -  Ongoing treatment with Gemfibrozil or Rifampicin (CYP2C8 inhibitor or inducer
                  respectively); or with Miconazole or phenylbutazone (increased hypoglycemic
                  effect of gliclazide).

               -  Previous diagnosis of osteoporosis

               -  Pregnancy, lactation or a female planning to conceive within the study period

               -  Any other significant medical reason for exclusion as determined by the
                  investigator