Background Globally, diabetic nephropathy (DN) represents a major contributor to chronic kidney disease and end-stage renal failure. Elevated blood pressure in individuals with diabetes plays a key role in the development of diabetes-related vascular complications. This study examined differences in clinical parameters between T2DM patients with and without DN, as well as variations in laboratory findings among these patients in relation to their antihypertensive and antidiabetic therapies. Methods: This retrospective cohort study involved comparing biomarkers across different drug groups in patients with and without diabetic nephropathy. A purposive sampling method was employed. Data analysis was conducted using SPSS, with the Wilcoxon signed-rank test for within-group comparisons and the Mann–Whitney U test for between-group comparisons. Descriptive statistics were generated to summarise patients’ sociodemographic characteristics. A p-value of < 0.05 was considered indicative of statistical significance. Results: A total of 271 patients were included in the study, of whom 88 patients developed DN. Based on differences in clinical biomarkers, glycated haemoglobin (HbA1c) and systolic blood pressure were significantly higher in the DN group, while estimated glomerular filtration rate (eGFR) was significantly lower at the end of the study. No between-group differences were observed in the lipidemic profile of patients. Decline in eGFR was significant in patients on calcium channel blockers, whereas patients in both groups on angiotensin-converting enzyme inhibitors (ACE) had improved eGFR. In both non-DN and DN patients, ACE inhibitors had a dominant effect on reducing systolic and diastolic blood pressure (p = 0.001). At the same time, the improvement in eGFR was greater in patients on ACE inhibitors. Metformin alone decreased HbA1c by 0.4% in non-DN patients, and the difference from baseline was significant. Furthermore, a significant improvement in body mass index was observed in the non-DN group. HbA1c was significantly improved in DN and non-DN patients on insulin therapy. A significant increase in BMI (0.8 kg/m2) was observed in non-DN patients who were taking insulin. Conclusion: Patients with DN demonstrated higher BMI values, reinforcing the link between obesity and diabetic kidney disease. Patients on ARBs and ACEi showed no significant differences in clinical parameters; however, eGFR declined significantly in patients on CCB. Regular monitoring of key biomarkers and timely intervention are crucial to prevent or delay DN progression, particularly in patients with identified risk factors.