Chronic kidney disease is associated with progressive renal dysfunction, cardiovascular complications and premature mortality. Diabetes is a leading cause of CKD, and the coexistence of these disorders complicates pharmacotherapy because declining kidney function affects drug selection and susceptibility to treatment-related adverse events [1,2]. Diabetic kidney disease reflects intertwined metabolic, hemodynamic and inflammatory mechanisms. Hyperglycemia, elevated intraglomerular pressure, oxidative stress and fibrosis contribute to albuminuria and declining eGFR. Glycemic control, blood pressure treatment and renin–angiotensin system blockade remain important, but substantial residual kidney risk persists. SGLT2 inhibitors reduce proximal tubular glucose and sodium reabsorption, increase distal sodium delivery and restore tubuloglomerular feedback. The DAPA-CKD and EMPA-KIDNEY trials showed substantial reductions in kidney disease progression and related outcomes with dapagliflozin and empagliflozin [3,4]. GLP-1 receptor agonists improve glucose-dependent insulin secretion and satiety, and the FLOW trial demonstrated kidney outcome benefits with semaglutide in T2DM and CKD [5]. Different mechanisms may yield different short-term effects on HbA1c, body weight, albuminuria and adverse events. This study compared three contemporary antidiabetic treatments among patients with T2DM and CKD in a tertiary-care teaching hospital in Telangana. 2. Aim and Objectives To compare the short-term effectiveness and safety of dapagliflozin, empagliflozin and semaglutide in patients with T2DM and CKD. The primary outcome was change in HbA1c at 12 weeks; secondary outcomes included fasting glucose, eGFR, UACR, weight, blood pressure, adverse events and treatment discontinuation.

Study design and setting A hospital-based comparative observational study was undertaken in association with the Department of Pharmacology, Maheshwara Medical College, Isnapur, Sangareddy, Telangana, from August 2025 to January 2026. Participants Seventy-five adults with T2DM and CKD were categorized according to treatment: dapagliflozin (n=25), empagliflozin (n=25), or semaglutide (n=25). Treatments were prescribed according to clinical considerations rather than random allocation. Eligibility Adults aged 30–75 years with T2DM and established CKD stages G2–G4 were eligible. CKD required markers of kidney damage or reduction in kidney function persisting for at least three months. Exclusions included type 1 diabetes, dialysis, renal transplantation, acute kidney injury, pregnancy and contraindications to the study drugs. Treatment exposure Common reference regimens were dapagliflozin 10 mg or empagliflozin 10 mg orally once daily and weekly subcutaneous semaglutide initiated at 0.25 mg with subsequent titration. Concomitant antidiabetic and antihypertensive therapy was documented. Clinical assessment HbA1c, fasting and postprandial glucose, serum creatinine, eGFR, UACR, body weight and blood pressure were assessed at baseline and follow-up, with an endpoint at week 12. Adverse drug reactions were recorded through patient interviews and clinical evaluation. Statistical analysis Means ± SD or medians summarized continuous measurements and counts (%) categorical outcomes. Analysis of variance or Kruskal–Wallis tests were used for between-group comparisons, and categorical events were evaluated using chi-square or Fisher exact tests as appropriate. Two-sided p<0.05 was considered significant. Observational contrasts were not interpreted as causal treatment effects.

The study cohort included 75 participants (44 men, 58.7%; 31 women, 41.3%). The overall mean age was 57.8 ± 9.4 years. Baseline characteristics were broadly comparable across the three treatment groups. Table 1. Baseline demographic and clinical characteristics Parameter Dapagliflozin (n=25) Empagliflozin (n=25) Semaglutide (n=25) p-value Age (years) 57.2 ± 9.1 58.4 ± 9.8 57.8 ± 9.5 0.906 Male, n (%) 15 (60%) 14 (56%) 15 (60%) 0.948 Female, n (%) 10 (40%) 11 (44%) 10 (40%) 0.948 Diabetes duration (years) 10.2 ± 4.1 10.8 ± 4.5 11.1 ± 4.3 0.755 BMI (kg/m²) 28.1 ± 3.6 28.5 ± 3.9 29.2 ± 4.0 0.589 HbA1c (%) 8.5 ± 0.9 8.6 ± 1.0 8.7 ± 0.9 0.752 FBG (mg/dL) 174.2 ± 26.5 178.4 ± 28.1 181.6 ± 29.3 0.639 eGFR 48.6 ± 12.4 47.9 ± 13.1 49.2 ± 12.7 0.936 Systolic BP (mmHg) 138.2 ± 13.4 139.1 ± 14.0 137.6 ± 13.8 0.928 CKD stage G3a represented the largest category (29/75, 38.7%), followed by G3b (23/75, 30.7%). Table 2. Distribution of CKD G stages CKD stage Dapagliflozin Empagliflozin Semaglutide Total n (%) G2 (eGFR 60–89) 4 3 4 11 (14.7%) G3a (45–59) 10 10 9 29 (38.7%) G3b (30–44) 7 8 8 23 (30.7%) G4 (15–29) 4 4 4 12 (16.0%) Total 25 25 25 75 (100%) The greatest HbA1c reduction occurred in the semaglutide group (1.3 ± 0.5 percentage points), compared with 0.8 ± 0.4 and 0.9 ± 0.4 in the dapagliflozin and empagliflozin groups (p<0.001). Table 3. Glycemic outcome measures at 12 weeks Parameter Dapagliflozin Empagliflozin Semaglutide p-value Baseline HbA1c (%) 8.5 ± 0.9 8.6 ± 1.0 8.7 ± 0.9 0.752 Week 12 HbA1c (%) 7.7 ± 0.8 7.7 ± 0.8 7.4 ± 0.7 0.285 HbA1c reduction (points) 0.8 ± 0.4 0.9 ± 0.4 1.3 ± 0.5 <0.001 Baseline FBG (mg/dL) 174.2 ± 26.5 178.4 ± 28.1 181.6 ± 29.3 0.639 Week 12 FBG (mg/dL) 143.6 ± 23.8 142.1 ± 24.6 131.2 ± 22.5 0.139 FBG reduction (mg/dL) 30.6 ± 15.2 36.3 ± 16.1 50.4 ± 18.6 <0.001 PPG reduction (mg/dL) 42.5 ± 20.3 46.8 ± 21.1 61.2 ± 22.6 0.005 Albuminuria declined in each group, with median percentage decreases of 22.4%, 25.8% and 18.6%. Changes in eGFR were modest over 12 weeks. Table 4. Kidney function and albuminuria outcomes Parameter Dapagliflozin Empagliflozin Semaglutide p-value Baseline eGFR 48.6 ± 12.4 47.9 ± 13.1 49.2 ± 12.7 0.936 Week 12 eGFR 47.3 ± 12.1 46.9 ± 12.8 49.0 ± 12.5 0.829 eGFR change −1.3 ± 3.8 −1.0 ± 3.5 −0.2 ± 3.2 0.520 Median baseline UACR (mg/g) 342 358 336 — Median week 12 UACR (mg/g) 265 266 273 — Median UACR reduction (%) 22.4 25.8 18.6 0.041 Body-weight reductions were 2.3 ± 1.3 kg, 2.5 ± 1.4 kg and 4.5 ± 2.0 kg for dapagliflozin, empagliflozin and semaglutide, respectively (p<0.001). Table 5. Weight and blood pressure outcomes Parameter Dapagliflozin Empagliflozin Semaglutide p-value Baseline weight (kg) 76.4 ± 10.3 77.1 ± 11.0 79.5 ± 11.6 0.579 Week 12 weight (kg) 74.1 ± 10.1 74.6 ± 10.8 75.0 ± 11.1 0.960 Weight reduction (kg) 2.3 ± 1.3 2.5 ± 1.4 4.5 ± 2.0 <0.001 Baseline systolic BP 138.2 ± 13.4 139.1 ± 14.0 137.6 ± 13.8 0.928 Week 12 systolic BP 132.8 ± 12.6 133.4 ± 12.8 134.1 ± 13.1 0.937 Systolic BP reduction 5.4 ± 6.2 5.7 ± 6.5 3.5 ± 5.8 0.365 At least one adverse event was reported in 24 patients (32.0%). Genitourinary events predominated in SGLT2 inhibitor groups, while gastrointestinal symptoms occurred more frequently with semaglutide. No severe hypoglycemia or diabetic ketoacidosis was recorded. Table 6. Treatment-emergent adverse events Adverse event Dapagliflozin n (%) Empagliflozin n (%) Semaglutide n (%) Genital mycotic infection 3 (12%) 2 (8%) 0 (0%) Urinary tract infection 2 (8%) 2 (8%) 0 (0%) Polyuria 3 (12%) 3 (12%) 0 (0%) Volume depletion symptoms 1 (4%) 2 (8%) 0 (0%) Nausea 1 (4%) 1 (4%) 6 (24%) Vomiting 0 (0%) 0 (0%) 3 (12%) Constipation 0 (0%) 0 (0%) 2 (8%) Mild hypoglycemia 1 (4%) 1 (4%) 1 (4%) Serious adverse events 0 (0%) 0 (0%) 0 (0%) A participant could report more than one adverse event. Table 7. Treatment completion Outcome Dapagliflozin Empagliflozin Semaglutide Completed treatment 23 (92%) 24 (96%) 22 (88%) Discontinued treatment 2 (8%) 1 (4%) 3 (12%) Discontinued due to adverse events 1 (4%) 1 (4%) 2 (8%) Other discontinuation 1 (4%) 0 (0%) 1 (4%)

Glycemic effectiveness All three drug groups showed improvements in glycemic indices over 12 weeks. Semaglutide demonstrated the greatest mean decline in HbA1c, consistent with its effects on glucose-dependent insulin secretion, glucagon suppression, satiety and weight loss. The glucose-lowering effect of SGLT2 inhibitors depends partly on filtration of glucose and may diminish with lower eGFR, even where their kidney and cardiovascular benefits persist. Albuminuria and kidney function UACR declined across treatment groups, with numerically greater reductions in the two SGLT2 inhibitor groups. SGLT2 inhibition modifies tubuloglomerular feedback and intraglomerular pressure, consistent with organ-protective mechanisms demonstrated in the DAPA-CKD and EMPA-KIDNEY trials [3,4]. Modest early eGFR decreases with SGLT2 inhibition can reflect reversible hemodynamic effects rather than sustained kidney injury. Twelve-week eGFR changes do not establish long-term renal protection. Weight and blood pressure Semaglutide was associated with the greatest weight reduction, which is mechanistically consistent with increased satiety and reduced energy intake. SGLT2 inhibitors also produced weight loss and numerically greater decreases in systolic blood pressure through urinary glucose and sodium excretion. Between-group blood pressure differences were not statistically significant. Safety and tolerability The pattern of adverse events aligned with known class effects: genital mycotic infections, polyuria and volume depletion with SGLT2 inhibitors, and nausea, vomiting and constipation with semaglutide. Although severe hypoglycemia was absent, associated insulin or sulfonylurea treatment can alter hypoglycemia risk. Patient selection and monitoring should account for volume status, eGFR, gastrointestinal tolerability and background medication. Implications and limitations KDIGO guidance supports SGLT2 inhibitors in eligible people with T2DM and CKD and long-acting GLP-1 receptor agonists when individualized glycemic targets remain unmet or use of preferred agents is unsuitable [1,2]. The small group sizes, nonrandomized treatment selection, potential baseline confounding, and short observation period constrain comparative inference. Kidney failure, cardiovascular outcomes and long-term eGFR slope cannot be estimated from these data.

Dapagliflozin, empagliflozin and semaglutide were associated with improvements in short-term metabolic outcomes in patients with T2DM and CKD. Semaglutide showed the greatest mean HbA1c and body-weight reductions, whereas SGLT2 inhibitor groups showed numerically larger albuminuria decreases. Adverse-event patterns differed according to pharmacological class. Individualized selection and monitoring remain essential, and longer controlled follow-up is needed to compare durable kidney and cardiovascular outcomes.

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