Randomized Clinical Trial to Evaluate the Effect of Dapagliflozin in Patients With Diabetic Macular Edema

Inclusion criteria:

• Type II diabetes mellitus patients, treated with premixed insulin and metformin, anddiagnosed with center-involved diabetic macular edema (CiDME)

• Presence of retinal thickening involving the center of the fovea (CiDME) in thestudy eye on Optical Coherence Tomography (OCT) Heidelberg Spectralis; If both eyesare eligible, the eye with the greater central subfield thickness on OCT is selectedas the study eye.

• Decreased visual acuity primarily attributable to DME

• Clear ocular media and pupillary dilation for adequate retinal imaging

• Ability to understand the study procedures and willingness to provide writteninformed consent

Study participant exclusion criteria:

• Patients below 18 years old and patients above 85 years old

• Patients with type I diabetes mellitus (Insulin dependent diabetes mellitus IDDM)

• Pregnant women and lactating women diagnosed with diabetes or intending to becomepregnant in the next 12 months

• Patients who had myocardial infarction within 3 months prior to screening

• Patients who had transient ischemic attack (TIA), ischemic or hemorrhagic strokewithin 3 months prior to screening

• Patients with poorly controlled diabetes mellitus, defined as patients havingglycosylated hemoglobin (HbA1c) level of ≥12% at screening or patients who werehospitalized for diabetic ketoacidosis or hyperosmolar coma within 4 months prior toscreening

• Patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 atscreening

• Patients with severe hepatic impairment of Child-Turcotte-Pugh class C at screening

• Patients treated with antidiabetic drugs thiazolidinediones (TZD) (rosiglitazone andpioglitazone) prior to screening

• Patients who were receiving SGLT2 inhibitors (e.g., dapagliflozin, canagliflozin, orempagliflozin) within 3 months prior to screening

• Known allergy or hypersensitivity to any component of the study drugs

• Current or previous participation in another clinical study involving the systemicor ocular administration of an investigational drug or device within 6 months ofscreening

Study eye exclusion criteria:

• Macular edema caused by other conditions than diabetic macular edema or coexistingwith DME such as retinal vein occlusion, choroidal neovascularization (CNV), oruveitic cystoid macular edema

• History of postoperative cystoid macular edema (Irvine-Gass syndrome)

• Cataract extraction within 3 months prior to screening

• Patients who had previous macular laser treatment

• Patients who had peripheral panretinal photocoagulation laser (PRP) treatment within 6 months prior to screening

• Patients who have been treated with intravitreal anti-VEGF or intravitrealcorticosteroids within 6 months prior to screening

• The use of corticosteroids or non-steroidal anti-inflammatory eye drops within 1month prior to screening

• Patients on topical prostaglandin analogs (e.g., latanoprost, travoprost, ioprost,or tafluprost) at screening

• History of vitrectomy or scleral buckling

• Presence of diffuse vitreomacular traction or thick epiretinal membrane on OCTcausing significant traction

• Presence of tractional retinal detachment involving the macula and requiringvitrectomy

• Presence of other associated macular pathology (e.g., macular scars or macularholes) on OCT

• Presence of rubeosis iridis

• Signs of hypertensive retinopathy (arterioral spasm or silver wiring of bloodvessels)

• Presence of glaucoma

• Aphakia

• Yttrium aluminum garnet (YAG) laser capsulotomy within 3 months prior to screening

• Patients diagnosed with ocular surface infections until treated prior to receivingthe intravitreal injections

Non-study eye exclusion criteria:

• The non-study eye receiving simultaneous intravitreal anti-VEGF treatment with the study eye