Background: Promising results of clinical trials involving SGLT2 inhibitors urge every clinician managing diabetes to use them. However, upcoming real-world data still show increased incidence of adverse events, but efficacy is comparable to clinical trials. Objectives: Genitourinary infection is the most commonly reported adverse effect with SGLT2 inhibitors. We evaluated effectiveness of patient screening protocol and advice of hygiene and hydration to avoid adverse effects of SGLT2 inhibitors in real-world setting. Method: This was a prospective observational longitudinal study which included consecutive subjects with uncontrolled T2DM recommended with SGLT2i after a simple screening protocol from December 2017 to November 2018. The adverse effects and metabolic parameters were evaluated at 1st, 3rd, 6th, and 12th months for each patient. Results: Of 413 patients recommended for SGLT2 inhibitors, 335 patients started the medication. At baseline, average age, glycosylated haemoglobin (HbA1c), and weight were 53 years, 9.5%, and 82 kg, respectively. Data of 332, 299, 270, and 231 patients were available at the 1st, 3rd, 6th, and 12th months for safety follow-up, respectively. Genitourinary tract infection was the most common adverse effect (8%) followed by ketosis (4%). Two patients needed to stop the drug permanently due to recurrent transient ischaemic attack and emphysematous pyelonephritis. Significant reduction in mean weight and HbA1c was observed at 6 months ( n = 270): 2.9 kg and 1.1%, respectively, and at 12 months ( n = 231): 3.8 kg and 1.6%, respectively. Conclusion: Simple screening protocol for patients considered for SGLT2i significantly reduced incidence of genitourinary adverse events.