strong predictor for DN (135). Serum adiponectin was proved as a strong predictor of DN in both type 1 and type 2 diabetic patients according to a recent meta-analysis of 13 studies of more than 5,000 cases (136). CONCLUSION SGLT2Is, GLP1RAs, and DPP4Is represent a new hope in preventing or slowing down the rate of progression of DN. Their favorable effect on body weight and the decreased likelihood of hypoglycemia promote their use even in T1DM. The rapidly accumulating evidence of the significant renal and cardiac protective effects of SGLT2Is and GLP-1RAs has enforced the ADA, EASD, ACE, and AACE to recommend their use as second-line treatment in T2DM patients with cardiovascular disease or CKD (127, 128, 137). However, all the available evidence has supported the impact of these agents in secondary prevention. The lack of similar significant evidence on the impact of these agents in primary prevention is likely due to the relatively short duration of the available trials. United Kingdom Prospective diabetes study (UKPDS) is the most famous primary prevention trial in T2DM patients. The results of this study failed to show any significant impact of the tight sugar control on the cardiovascular endpoints at the end of the study. Ten more years after the end of the study were needed to get significant differences in acute myocardial infarction and overall mortality (138). The planned duration of the CREDENCE trial was 5.5 years. This study was then prematurely terminated when a significant difference in the composite endpoints between the two arms in the whole group became evident (125). This shortened duration could explain why patients with eGFR ≥60 mL/ min/1.73 m2 and patients with UAE ≤1,000 mg/gm creatinine failed to get the expected benefit. The most recent DECLARE-TIMI 58 study has supported this view. This last study continued for 4.2 years and showed the significant impact of dapagliflozin in patients having baseline GFR >90, those with GFR between 60 and 90, and even in normoalbuminuric patients (12). The pronounced effects in patients of DECLARE study are likely due to the relatively longer duration of follow-up. Based on these facts, it seems that more lengthy primary preventive studies are needed. Such studies should recruit newly diagnosed T2DM patients who have laboratory markers suggesting the likelihood to develop DN. The very high cost is main obstacle for these studies as the duration needed to get enough endpoints for adequate statistical analysis is very long. Given the documented safety and superiority of SGLT2Is, GLP1RAs, and DPP4Is, we suggest a more reproducible approach to manage T2DM patients. Routine tests for novel predictors screening for the likelihood to develop DN should be done in all T1DM and T2DM patients. Serum MBL, fibrinogen, or adiponectin can help to select patients prone to develop DN. These patients should be prescribed SGLT2Is aiming at prevention instead of waiting until signs of renal involvement develop. This primary prevention approach will supposedly abort the development of DN instead of the current secondary prevention approach that only postpones ESRD for few months or years. The primary prevention should be extended to involve T1DM patients but with great attention to insulin treatment in order to avoid diabetic ketoacidosis. Although this preventive approach caries some risk especially in T1DM, the benefits obtained will definitely outweigh the drawbacks. Development of ESRD in diabetic patients is a real nightmare for nephrologists. Morbidity and mortality are significantly higher among diabetic patients starting dialysis compared with non-diabetic patients (139, 140). 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