Dapagliflozin Treatment in Type 2 Diabetes

Inclusion Criteria: * Provision of signed and dated, written informed consent prior to any study-specific procedures. * Female and/or male aged between 18 years and less than or equal to 80 years. * A diagnosis of T2DM with HbA1c ≥6.5% (≥48 mmol/mol) and =11% (\<97 mmol/mol); and eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2. * Patient specific optimal antihypertensive dose of an ACEi or ARB (as per Investigator's judgement) for at least 6 weeks prior to Visit 4 (Day 1). * A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator. Metformin, sulphonylurea, DPP4 inhibitors or any combinations of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required. * Suitable veins for cannulation or repeated venipuncture. * Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of study drug to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used. * Patient specific optimal antihypertensive dose of an ACEi or ARB (as per Investigator's judgement) for at least 6 weeks prior to Visit 4 (Day 1). * A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator. Metformin, sulphonylurea, DPP4 inhibitors or any combination of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required. Exclusion Criteria: * Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 6 months prior to Screening Visit (Visit 1). * Involvement in the planning and conduct of the study (applies to both UMCG staff and staff at third party vendor or at investigational sites). * Hypersensitivity to dapaglifozin, indocyanine green, sodium iodide, or iodine, or patients who have poorly tolerated indocyanine green in the past. * Pacemaker or other implanted electronic devices. * Pregnancy. * Breastfeeding. * Known clinically significant disease or disorder; or clinically relevant abnormal findings in physical examination, clinical chemistry, haematology and urinalysis; or unstable or rapidly progressing renal disease; other dietary restrictions that would make it difficult for the subject to follow the protocol required diet plan or any other condition or minor medical complaint, which, in the opinion of the investigator, may either put the patient atrisk because of participation in the study, or influence the results, or the patient's ability to participate in the study and comply with study procedures, restrictions and requirements. * Diagnosis of T1DM. * Hyperthyroidism or autonomic thyroid adenomas. * Abnormal vital signs, after 10 minutes supine rest, defined as any opf the following (Visit 1); Systolic blood pressure above 180mmHg; Diastolic blood pressure above 110 mmHg; Pulse less than 50 bpm or greater than 100 bpm. * Any of the following cardiovascular/vascular within 3 months prior to signing the consent at Visit 1, as assessed by the Investigator: myocardial infarction, cardiac surgery or revascularization (coronary artery bypass graft \[CABG\]/ percutaneous transluminal coronary angioplasty \[PTCA\], unstable angina, unstable heart failure, heart failure New York Association Class IV, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia. * Patients with severe hepatic impairment (Child-Pugh C). * Ongoing weight-loss diet (hypocaloric diet) or use of weight-loss agents, unless the diet or treatment has been stopped at least 3 months before Screening Visit, ensuring patients having a stable body weight with no verified body weight variability of greater then 3 kg during the 3 months before Screening Visit. * Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying. * History of bladder cancer. * Non-diabetic kidney disease. * UACR greater than 1000 mg/g per day at the Screening Visit based on spot urine sample (quantitative assessment). * Current chronic use of the following medication: glucagon-like peptide receptor agonists or thiazolidinediones, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. * Receiving immunosuppressive or other immunotherapy for primary or secondary renal disease within 6 months prior to Screening Visit (Visit 1). * Current treatment or treatment within the last 2 weeks prior to Screening Visit (Visit 1) with mineralocorticoid antagonists (loop or thiazide diuretics are allowed as long as they are used in stable dose for at least 4 weeks prior to screening). * A metformin dose which is outside the specified dose range for renal impairment according to local guidelines and/or Investigator's judgement. * Medicinal products and substances that can reduce or increase absorption of indocyanine green; anticonvulsants, bisulphite compounds, haloperidol, heroin, meperidine, metamizol, methadone, morphium, nitrofurantoin, opium alkaloids, phenobarbital, phenylbutazone (reduced absorption), and cyclopropane, probenecid, rifamycin (increased absorption).