Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Controlled Trial for People With Established Type 2 Diabetes During Ramadan: Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen: The 'Can Do Ramadan' Study
Brief Summary: This study aims to determine if the addition of Canagliflozin (Invokana™) therapy to monotherapy of metformin is more effective at achieving the double composite endpoint of a reduction in HbA1c (≥ 0.3%) and weight loss (≥1kg) 3-4 weeks post-Ramadan. The study will also include patients currently on dual therapy, specifically metformin plus a sulphonylurea, pioglitazone or repaglinide to determine whether switching to metformin plus Canagliflozin (Invokana™) is more effective at achieving the composite endpoint compared to those remaining on previous dual therapy. There are a number of secondary outcomes including weight loss, rates of hypoglycaemia, blood pressure and a number of biochemical endpoints.


Options:
A: Inclusion Criteria:

* Muslim men and women with type 2 diabetes
* Participants who intend to fast during the month of Ramadan
* Participants who have been on a stable dose of sulfonylurea for at least three months

Exclusion Criteria:

* Participants with type 1 diabetes mellitus
* Pregnant or breast feeding women
* Participants with hypersensitivity or contraindication to dipeptidyl peptidase (DPP-4) treatment
* Participants on insulin
* Participants on any class of oral diabetic therapy other than sulfonylurea or metformin
B: Inclusion Criteria:

* Type 2 diabetes diagnosed by a physician at least six months prior to study enrollment. This will be determined via self-report with verification (medical records, current treatment, or test results meeting the 2009 Malaysian Clinical Practice Guideline for Management of Type 2 Diabetes Mellitus (4th edition) criteria of fasting blood glucose \> 7.0 mmol/L , symptoms of hyperglycaemia with casual plasma glucose \>11.1mmol/L or two-hour plasma glucose \>11.1mmol/L after a 75gram oral glucose load)
* HbA1c of \> 7.5% but less than 11.0% within the most recent 3 months. Individuals with HbA1c exceeding this level may require more urgent care and as such will be asked to seek treatment
* Aged 18 - 75 years are eligible. Participants older than 75 years of age are excluded due to the increased risk of competing mortality and potential safety concerns related to hypoglycaemia
* Willing or has an intention to fast for at least 15 days during Ramadan
* Access to internet and an e-mail address , or access to a smartphone with 3G services in the intervention group
* Not pregnant or history of heart diseases, serious illness, cancer diagnosis or any other conditions that can impede participation

Exclusion Criteria:

* Unable or unwilling to give informed consent or communicate with local study staff
* Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder
* Hospitalization for depression in past six months
* Plans to relocate to an area or travel plans that do not permit full participation in the study
* Lack of support from primary health care provider or family members
* History of bariatric surgery, small bowel resection, or extensive bowel resection
* Currently pregnant or nursing
* Cancer: requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured or in the opinion of the investigator carry an excellent prognosis (e.g., Stage 1 cervical cancer)
* Cardiovascular disease (heart attack or procedure within the past three months or participation in a cardiac rehabilitation program within last three months, stroke or history/treatment for transient ischemic attacks in the past three months, or documented history of pulmonary embolus in past six months)
* Other medical, psychiatric, or behavioral factors that in the judgment of the Principal Investigator may interfere with study participation or the ability to follow the intervention protocol
C: Inclusion Criteria

1. Able, in the opinion of the Investigator, and willing to give informed consent
2. Age ≥ 25 years old
3. Established T2DM (≥ 3 months) on stable dose monotherapy (metformin only for ≥ 8 weeks prior to enrolment) OR stable dose dual therapy (metformin plus either repaglinide, a sulphonylurea or pioglitazone or DPP-4 inhibitor for ≥ 8 weeks prior to enrolment)
4. HbA1c between 6.6 - 11% (49mmol/mol - 97mmol/mol) at the screening visit
5. Individuals intending to fast during the holy month of Ramadan

Exclusion Criteria

1. Unable, in the opinion of the Investigator, and unwilling to provide informed consent
2. Aged \< 25 years old
3. Established T2DM (≤ 3 months) on medication for fewer than 8 weeks prior to enrolment
4. HbA1c ≤6.5 and ≥11.1%
5. Individuals not intending to fast during the holy month of Ramadan
6. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. The latter includes avoiding sex, hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or not heterosexually active. Furthermore, subjects who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at baseline.
7. Suffer from terminal illness
8. Have renal disease that requires immunosuppressive therapy, dialysis or transplant
9. Have nephrotic syndrome or inflammatory renal disease
10. Have an estimated glomerular filtration rate (eGFR) \<60ml/min/1.73m2 at screening
11. Have serum creatinine levels \>132.6μmol/L for men or \>123.8μmol/L for women
12. Impaired liver function (ALAT ≥ 2.5 times upper limit of normal)
13. Known Hepatitis B antigen or Hepatitis C antibody positive
14. Clinically significant active cardiovascular disease (including history of myocardial infarction, unstable angina, previous revascularization procedure or cerebrovascular accident) within the past 6 months before screening
15. Have uncontrolled hypertension (defined as systolic blood pressure ≥180mm/Hg and diastolic ≥100mm/Hg in the supine position after \>5minutes rest with confirmed compliance to antihypertensive medication)
16. Heart failure (NYHA class III and IV) at the discretion of the investigator
17. Previous history of recurrent major hypoglycaemia as judged by the study clinician
18. Known or suspected allergy to the study product
19. Receipt of any investigational drug within four weeks prior to this study
20. Has had previous treatment with a GLP-1 receptor agonist, insulin, or another SGLT2 inhibitor within 12 weeks of screening
21. Have severe and enduring mental health problems
22. Are not primarily responsible for their own care
23. Are receiving insulin therapy
24. Type 1 diabetes
25. Any contraindication to sulphonylureas, repaglinide, pioglitazone and/or DPP-4 inhibitors
26. Have severe irritable bowel disorder
27. Have hereditary glucose-galactose malabsorption
28. Have primary renal glycosuria
29. Patients who have participated in another study of an investigational medicinal product in the last 3 months
30. High risk of bone fracture (undiagnosed osteoporosis) as determined by the WHO FRAX tool
31. Evidence of excessive and compulsive drinking of alcohol i.e. alcohol abuse as determined by the Fast Alcohol Screening Test (FAST)
32. Individuals on a severe calorie restricted diet \<800cals/day
33. Has a surgical procedure booked in the next 12 months
34. Has a history of chronic pancreatitis
35. Has latent autoimmune diabetes in adults (LADA)
36. Individuals on loop diuretics
37. Any contraindication to the IMP
D: Inclusion Criteria:

* Muslim, with type 2 diabetes mellitus
* Intends to fast during the month of Ramadan
* Hemoglobin A1c (HbA1c) ≤10% at screening
* On a stable dose of a SU drug (glibenclamide, glimepiride, or gliclazide), for at least three months, with or without metformin therapy at a stable dose

Exclusion Criteria:

* Type 1 diabetes mellitus
* Pregnant or breast feeding or with gestational diabetes
* Hypersensitivity or contraindication to dipeptidyl peptidase-4 (DPP-4) treatment
* Serum creatinine ≥1.5 mg/dL (males), ≥1.4 mg/dL (females)
* History of severe hypoglycemia (defined as a hypoglycemic event requiring the assistance of another individual, and/or resulting in a emergency department admission, physician office visit and/or hospitalization)
* Any use of insulin (prior to or during Ramadan)
* Use of any class of oral antidiabetic therapy other than an SU or metformin
* Current participation in another interventional study

Answer: C