Acute renoprotective effects of dapagliflozin monotherapy on albuminuria and metabolic derangements in newly diagnosed type 2 diabetes mellitus: a quasi-experimental study

Abstract

Background

Diabetic kidney disease (DKD) is a globally prominent microvascular sequela of Type 2 Diabetes Mellitus (T2DM), making effective early prevention paramount. The well-established cardiorenal benefits of sodium-glucose co-transporter 2 inhibitors (SGLT2i) are largely derived from studies on patients with T2DM. Clear evidence is lacking to support the use of SGLT2i as a first-line monotherapy in newly diagnosed T2DM patients who have not yet initiated other glucose-lowering or protective agents. This study aimed to fill this knowledge gap by assessing the acute impact of Dapagliflozin on reducing albuminuria and correcting metabolic derangements during this critical early disease window to halt disease progression at its onset.

Methods

This quasi-experimental study conducted over a 3-month intervention period, included 133 newly diagnosed T2DM patients (76 males, 57 females) with evidence of micro- or macro-albuminuria. All patients were treated with Dapagliflozin 10 mg/day, primary and secondary endpoints were assessed by cardiorenal markers (albumin-to creatinine ratio (ACR) and calculated glomerular filtration rate (GFR)), metabolic marker (HbA1c), Anthropometric parameters (BMI and blood pressure), were measured at baseline and follow-up, Paired t-tests were used for pre- and post-intervention analysis.

Results

Dapagliflozin significantly improved both metabolic and renal markers within the short follow-up period. The primary outcome, ACR, declined markedly from 108.44 mg/g to 65.79 mg/g (P < 0.001), representing a mean relative reduction of approximately 40%. Glycemic control was rapidly achieved, with a mean HbA1c drop from 9.04% to 7.31% (P < 0.001). While calculated GFR remained stable overall, a significant reduction in systolic blood pressure was also observed (P < 0.001).

Conclusion

Dapagliflozin demonstrates a rapid and multi-organ protective effect when introduced early in T2DM, achieving potent reduction in albuminuria and excellent glycemic control while preserving kidney function stability. These findings strongly support the integration of SGLT2i as a first-line therapy to mitigate cardiorenal risk from the earliest stages of T2DM.

Introduction

Diabetes mellitus (DM) is a critical public health concern with rapidly expanding prevalence, given its chronic, long-lasting effects on patient’s health and quality of life. Statistics reported that approximately 22 million people in the UK and similar geographical areas are currently afflicted. According to the Global Burden of Disease Study 2017, about 476 million people worldwide live with diabetes mellitus. Notably, Type 2 Diabetes Mellitus (T2DM) comprises the overwhelming majority of cases affecting 463 million patients [1].

The prevalence of T2DM in Palestine in 2010 was 15.3% and it’s expected to be 23.4% in 2030 [2], which is too high compared to the global prevalence of diabetes in 2015, which was 8.8%, and is expected to rise to 10.4% by 2040 [3].

T2DM is a multifactorial disorder, marked by high blood sugar due to issues with insulin action at the cellular level or the capacity for insulin secretion, or both [4]. Over time, sustained hyperglycemia in chronic diabetes leads to long term sequelae, include multi-organ morbidity affecting the eyes, nerves, kidney, feet, vasculature, and heart [5]. the duration of diabetes is consistently linked to the onset of microvascular complications which principally include retinopathy, neuropathy, and nephropathy [6]. As a result, glucose-lowering agents which address metabolic abnormalities that fuel disease advancement, are theorized to lower the incidence of such complications. Yet, the effectiveness of these agents in long term glucose homeostasis remains elusive for many patients [7].

The microvascular complications of diabetes particularly affect the kidney and lead to a condition termed as diabetic nephropathy (DN), which is the most prevalent T2DM complication [8]. and it is the leading cause of end-stage renal disease worldwide [6]. The severe consequences of diabetic nephropathy, which increase morbidity and mortality rates, impose a significant financial burden on patients with poorly managed diabetes, with approximated annual healthcare costs ranging from $8,000 to $43,000 [9]. DN develops in approximately 40% of patients with diabetes [10], after 10 years of T2DM were diagnosed [11]. DN is characterized by persistent albuminuria (or albuminuria excretion rate of > 300 mg/d or 200 µg/min) measured at least twice within three to 6 months interval, progressive decreasing in glomerular filtration rate (GFR) [12], which often occur in association with an elevate in blood pressure, ultimately leading to end-stage renal disease [13].

while the pivotal role of glycemic control agent is curving the progression of vascular damage, DN continues to be the foremost cause of end stage kidney disease (ESRD) [14]. Even with progress in glucose management strategies, DN sustained to be heavy toll on patients with T2DM. As a therapeutic necessity, novel pharmacological approaches, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, are expected to reduce the incidence of renal events and delay the progression toward dialysis dependency [15].

SGLT2 inhibitors have been recently introduced as antihyperglycemic agents. Extensive data support their safety in cardiovascular function and, surprisingly, their capacity in large-scale clinical trials to retard the progression of DN. Significantly, the protective effects of SGLT2 inhibitors in cardiorenal function have been shown to be independent of their primary glucose-lowering effect [16]. SGLT2 inhibitors work by lowering the kidney’s glucose threshold and preventing the reuptake of glucose and sodium in the proximal tubules by targeting the sodium-glucose co-transporter 2 located in those kidney structures, therefore, promoting the excretion of excess glucose and sodium in urine. SGLT2 inhibitors also promote sodium delivery to the distal convoluted tubule, which stimulates tubuloglomerular feedback causing afferent arteriolar contraction and decreased glomerular pressure.

Previous therapeutic approaches, while successful in managing glycemic control, did not adequately address the toxic effects of hyperglycemia and hyperlipidemia on local renal hemodynamics [17]. RAAS-blocking agents, like angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) for example don’t reverse the disease and are thought to be inadequate for DN [18, 19]. Treatment combinations, such as dual-RAAS blockade with ACE inhibitors and ARBs, have been considered, but they are associated with adverse events (e.g., hyperkalemia and acute kidney injury); thus, these treatment combinations are not recommended, and are contraindicated in patients with renal impairment [20]. Finally, even with treatment with currently available therapies, many patients with DN nevertheless progress to ESRD, requiring dialysis while kidney transplant is considered [21].

Through hemodynamic and non-hemodynamic mechanisms that include a reduction in inflammation, fibrosis, glomerular hyperfiltration, and oxidative stress, recent studies have confirmed the comprehensive protective role of SGLT2i in protecting against diabetic nephropathy by maintaining the integrity of the glomerular filtration barrier and thus decreasing protein leakage into the urine [22]. Subgroup analyses showed that the use of SGLT2i significantly reduced albuminuria by 40.78% in patients with moderate albuminuria. However, a smaller reduction of 28.40% was observed in patients with lower albuminuria (< 300 mg/g). This reinforces and confirms the therapeutic role of SGLT2i in effectively reducing albuminuria, regardless of differences in baseline levels [23].

Dapagliflozin particular, in addition to its effectiveness in controlling blood sugar levels, promoting weight loss and lowering blood pressure, it has a demonstrated clear benefits in preventing kidney complications of diabetes by reduce the excretion of albumin in kidneys. This is achieved through its positive effect in reducing hyperfiltration and tubular hypertrophy associated with diabetes, thus reducing the progression of long-term nephropathy. However, conclusive evidence is needed through clinical trials focusing on the renal benefits of SGLT2i in reducing and treating proteinuria [24].

Recent large-scale global studies involving more than 65,000 patients with type 2 diabetes compared the effects of SGLT2i and other antidiabetic drugs on preventing and reducing proteinuria and preserving kidney function. SGLT2i users experienced a slower decline of 1.53 ml/min per year (p < 0.0001) in estimated glomerular filtration rate (eGFR) compared to those using other treatments. Advanced cases, such as a fall in eGFR of more than 50% or the development of end-stage renal disease, were significantly lower in SGLT2i users, with 3 cases per 10,000 per year compared to 6.3 cases in the control groups. Slowing the decline in eGFR reduces the leakage of albumin into the urine, thus protecting the kidneys from diabetic complications [25].

This study focuses on newly diagnosed type 2 diabetes patients to better understand the early effects of SGLT2i on kidney function. This population is of particular interest because early intervention may offer the greatest potential to delay or prevent the progression of DN. Despite the growing evidence of the benefits of SGLT2i in managing diabetes-related complications, large long-term clinical trials are still needed to confirm their renal benefits in slowing the development and progression of DN [26]. moreover there is currently a gap in knowledge regarding their effects specifically in newly diagnosed patients. This gap highlights the need for focused studies to elucidate how early intervention with these agents may alter the trajectory of renal function in this demographic. Albuminuria, which can often present in newly diagnosed diabetic patients [24], is a key biomarker used to screen renal function and plays a central role in diagnosing DN and guiding treatment strategies [25]. By measuring proteinuria levels at baseline and again after three months of treatment with SGLT2i, we aim to assess their impact on renal health in newly diagnosed patients.

Conducting this research in Hebron is especially important, as the region faces unique healthcare challenges, including delays in diagnoses that contribute to the prevalence of proteinuria in newly diagnosed diabetic patients, and a growing diabetic population. By investigating the effectiveness of SGLT2i locally, we can generate context-specific data that could lead to improved diabetes management strategies for communities in Hebron and similar settings. This study has the potential to contribute not only to global knowledge but also to addressing critical health issues in our local population.

Methodology

Study design

This research employed a quasi-experimental design and was involved patients with newly diagnosed T2DM who also had proteinuria. SGLT2i were administered to evaluate their effect on proteinuria reduction. Pre-assessment of proteinuria was conducted before treatment, followed by a post-assessment after three months of SGLT2i use.

Study time and setting

The study was conducted at the Issa Medical Center. Data collection took place over a nine-month period, commencing in October 2024 and concluding in June 2025. Analysis and final submission were completed by October 2025.

Population

The population for this study consisted of newly diagnosed T2DM patients from Hebron who had not yet initiated any diabetes treatment and were prescribed SGLT2i for their management. Patients were included if they were over the age of 18 who had a confirmed diagnosis of T2DM and showed evidence of proteinuria at baseline, as measured by the ACR. Additionally, patients must not have previously used SGLT2i or other diabetes-related medications.

Patients with type 1 diabetes mellitus, advanced kidney disease with calculated GFR below 30 mL/min, and those with significant cardiovascular events such as stroke or unstable angina or advance liver disease were excluded from the study. Furthermore, pregnant or breastfeeding women, as well as individuals with any prior use of SGLT2i, and those with BMI < 18 kg/m² were not eligible to participate.

Sample size

Prior to commencement, the statistical power was assessed, which indicated a sample size of 32 participants to achieve the desired 80% power (assuming an effect size of 0.5 and p < 0.05). Additionally, to account for potential dropouts or non-compliance, additional participants was included, Subsequently, 133 participants completed the full three-month study protocol and were This large, successfully enrolled cohort provided substantial statistical strength, confirming the study’s ability to effectively demonstrate the efficacy of SGLT2i and to ensuring the reliability of statical finding of the final analysis.

Data collection and tool

Data were collected via two in-person patient visits over the three-month intervention period: a baseline visit and a follow-up visit. At the baseline visit, a complete medical history was recorded, and initial anthropometric measurements and laboratory tests (including HbA1c, RBS, ACR, and Serum Cr) were performed. The independent variable under study was the initiation of the oral Dapagliflozin 10 mg/day treatment. The data collection was specifically designed to track the dependent variables that assess treatment efficacy: the primary outcome was the change in proteinuria measured by the ACR, while secondary outcomes included changes in metabolic markers (HbA1c, RBS), cardiorenal parameters (calculated GFR, BP), and anthropometric measures (BMI, weight). Additionally, covariates such as age and gender were recorded. All information was maintained electronically using Google Sheets, and patient adherence was concurrently monitored through self-reports and pill counts.

Variables

This research analyzed several key variables. The independent variable was the administration of SGLT2i. The primary dependent variable investigated was the level of proteinuria, measured by the ACR after three months of treatment. Additionally, the study also considered secondary variables such as age, gender, BMI, RBS, HbA1c, BP, calculated GFR.

All laboratory analyses were performed in the same certified laboratory, using the same instruments and assay procedures, both at baseline and after the intervention, to ensure consistency and reliability of results.

Urine albumin-to-creatinine ratio (ACR)

Urinary albumin concentration was measured using an immunoturbidimetric assay on a Humalyzer 4000 (semi-automated chemistry analyzer), REF 18,250, Human, with reagent kits supplied by GIESSE Diagnostics (catalog no. 22135). Urinary creatinine was measured using the Jaffe method on the same analyzer, with reagent kits supplied by Wiener.

The ACR was calculated as:

ACR (mg/g) = urine albumin (mg/L) ÷ urine creatinine (g/L).

If creatinine values were reported in mg/dL, they were converted to g/L by multiplying by 0.01. Results were expressed in mg/g.

patients were categorized according to ADA guidelines [27].

• Normal to mildly increased: <30 mg/g.

• Moderately increased: 30–300 mg/g.

• Severely increased: >300 mg/g.

Serum creatinine

Serum creatinine was measured using the compensated Jaffe method on a Humalyzer 4000 (semi-automated chemistry analyzer) with reagent kits supplied by Wiener (catalog no. 241061209). The assay was traceable to IDMS standards, and results were expressed in mg/dL. Quality control was performed according to manufacturer instructions.

Reference ranges:

• Males: 0.7–1.2 mg/dL.

• Females: 0.6–1.1 mg/dL.

Calculated GFR:

Cockcroft-Gault formula:

Creatinine Clearance (mL/min) = ((140 – Age) × Weight (kg) × [0.85 if female, 1 if male]) ÷ (72 × Serum Creatinine (mg/dL)).

Random blood sugar (RBS)

RBS was measured in serum using the glucose oxidase-peroxidase (GOD-POD) method on a Humalyzer 4000 (semi-automated chemistry analyzer) with reagent kits supplied by Human (catalog no. 10260). Results were expressed in mg/dL. Quality control was performed using manufacturer-provided control sera.

Glycated hemoglobin (HbA1c)

HbA1c was measured in whole blood (EDTA) using the Finecare HbA1c Rapid Quantitative Test (Fluorescence Immunoassay) with the Finecare FIA Meter (Models FS-112/FS-113/FS-114/FS-205). The assay is based on fluorescence immunoassay technology, in which the hemolyzed whole blood sample is mixed with a detection buffer and transferred to a test cartridge. The HbA1c concentration is measured quantitatively by the meter, and results are displayed as percentage (%).

The assay is NGSP-certified and traceable to the IFCC reference method. Results were reported both in percentage (%) and in mmol/mol. Conversion was based on the equation:

IFCC (mmol/mol) = (10.929 × NGSP %) – 23.50.

Quality control was performed using commercial control materials supplied by the manufacturer.

Reference ranges (ADA guidelines) [27]:

• Normal: <5.7% (< 39 mmol/mol).

• Prediabetes: 5.7–6.4% (39–46 mmol/mol).

• Diabetes: ≥6.5% (≥ 48 mmol/mol).

Anthropometric measurements (BMI)

Weight was measured using a calibrated digital scale (accuracy ± 0.1 kg) with participants wearing light clothing and no shoes. Height was measured using a stadiometer (accuracy ± 0.1 cm) with participants standing erect, barefoot, and with the head aligned in the Frankfort horizontal plane. Body mass index (BMI) was calculated as:

BMI (kg/m²) = weight (kg) ÷ [height (m)]².

Participants were categorized according to the WHO BMI classification [28]:

• Underweight: <18.5 kg/m².

• Normal weight: 18.5–24.9 kg/m².

• Overweight: 25.0–29.9 kg/m².

• Obesity class I: 30.0–34.9 kg/m².

• Obesity class II: 35.0–39.9 kg/m².

• Obesity class III: ≥40.0 kg/m².

Blood pressure (BP)

Blood pressure was measured using a validated automated sphygmomanometer with an appropriately sized cuff. Participants rested for at least 5 min in a seated position before measurement, refrained from walking or any strenuous activity for at least 1 h prior, and avoided caffeine consumption for at least 1 h before the test. Two readings were obtained at 1–2 min intervals, and the average was recorded. If the difference between readings exceeded 10 mmHg, a third measurement was taken and the mean of the last two readings was used.

Reference ranges (WHO/AHA classification) [29]:

• Normal: Systolic < 120 mmHg and Diastolic < 80 mmHg.

• Elevated: Systolic 120–129 mmHg and Diastolic < 80 mmHg.

• Hypertension stage 1: Systolic 130–139 mmHg or Diastolic 80–89 mmHg.

• Hypertension stage 2: Systolic ≥ 140 mmHg or Diastolic ≥ 90 mmHg.

• Hypertensive crisis: Systolic ≥ 180 mmHg or Diastolic ≥ 120 mmHg.

1. Baseline evaluation:

At the start of the study, all 133 enrolled patients underwent a comprehensive baseline evaluation this included:

• Demographic Variables: Recording of Age and Gender.

• Medical History: (diabetes diagnosis date, previous medications (if any), comorbidities (e.g., hypertension, dyslipidemia), and lifestyle factors (e.g., smoking, alcohol use).

• Anthropometric Measures and vitals (Secondary Variables): Measurement of height, Weight, BMI, blood pressure (SBP and DBP).

• 2.Baseline Laboratory Tests:

• Proteinuria (Primary Dependent Variable): ACR.

• Glycemic Control (Secondary Variables): HbA1c and RBS.

• Kidney Function (Secondary Variables): Serum Cr and calculated GFR.

Treatment protocol

Following the baseline assessment, All patients were initiated on the study drug: oral dapagliflozin 10 mg once daily, which serves as the Independent Variable. the intervention was maintained for 3 months.

3. Re-Evaluation after 3 months:

* laboratory.

• ACR: To measure changes in proteinuria levels.

• Blood Sugar and HbA1c: To track glycemic control.

• Serum Cr and calculated GFR: To monitor kidney function.

• BP: Monitor for any reductions related to SGLT2 inhibitors.

*Adherence: was monitored through self-reports and pill counts.

4. Outcome Measures:

• Primary Outcome:

◦ Reduction in proteinuria (as measured by changes in the ACR from baseline to 3 months).

• Secondary Outcomes:

Changes in body weight, BP, glycemic control (HbA1c and RBS), kidney function (calculated GFR changes).

Data analysis

the threshold for statistical significance was set at p < 0.05, data were analyzed by SPSS version 20, descriptive statistics were used to summarized the data, paired t-test were used to compare pre- and post-treatment measurements such as age, sex, BMI, and baseline proteinuria levels. Multivariate regression analysis will be conducted to evaluate the effect of SGLT2i on proteinuria, adjusting for relevant covariates.

Results

The study cohort consisted of a total of 133 newly diagnosed Type 2 Diabetes Mellitus patients, comprising 76 males (57.1%) and 57 females (42.9%) (Fig. 1).

Fig. 1.

Male and female distribution

Figure 2 shows the pre-medication BMI Panel A. Majority of patients were overweight (62%), followed by normal weight (29%), with smaller proportions in Obese I (8%) and Obese II (1%). Panel B(post-medication): After treatment, the proportion of normal-weight patients increased to 52%, while overweight decreased to 43%, and Obese I reduced to 5%.

Fig. 2.

BMI distribution before (A) and after (B) medication

Figure 3 Panel A (pre-medication): The majority of participants were in the moderately increased category (75%), followed by normal to mildly increased (18%) and severely increased (7%). Figure Panel B (post-medication): The proportion of participants with normal to mildly increased ACR rose to 30%, while moderately increased ACR decreased to 69%, and severely increased ACR dropped to 1%.

Fig. 3.

Distribution of urinary albumin-to-creatinine ratio (ACR) categories before (A) and after (B) treatment

The pooled data confirmed the overall broad-spectrum therapeutic benefit of the intervention. Mean HbA1c dropped from 9.043 to 7.314 (P < 0.001), reflecting excellent overall glycemic improvement. Significant mean reductions were also confirmed for Weight (from 82.17 to 78.29 kg; P < 0.001), SBP (from 134.53 to 125.41 mmHg; P < 0.001), and DBP (P = 0.001). The primary marker of kidney health, ACR, demonstrated a highly significant reduction from 108.44 to 65.79 (P < 0.001). The change in calculated GFR for the general population, however, was not statistically significant (mean pre: 96.15 to post: 98.64; P = 0.061), reflecting the stabilized response when both sexes were aggregated as seen in Table 1.

Table 1.

Metabolic and cardiorenal markers for the total population in pre and post intervention (N = 133)

Variable	Pre intervention		Post intervention		p-value
	Mean	SD*	Mean	SD*
weight	82.17	11.44	78.29	10.10	< 0.001
BMI	25.97	2.80	24.80	2.45	< 0.001
SBP	134.53	17.05	125.41	13.34	< 0.001
DBP	71.35	9.29	69.34	6.19	0.001
ACR	108.44	92.93	65.79	60.07	< 0.001
HbA1c	9.043	1.64	7.314	0.19	< 0.001
Cr	1.04	0.185	0.97	0.19	< 0.001
calculated GFR	96.15	22.86	98.64	25.16	0.061
RBS	206.37	72.01	162.38	38.49	< 0.001

Analysis of the female cohort revealed highly significant improvements across primary metabolic and cardiorenal markers. Glycemic control improved dramatically, with HbA1c decreasing from a mean of 9.28 to 7.35 (P < 0.001). This was accompanied by a clear reduction in Random Blood Sugar (RBS) (mean pre: 214.04 to post: 165.00; P < 0.001). Anthropometric benefits were also pronounced, as Weight decreased from 81.96 to 78.18 kg (P < 0.001). Crucially, cardiorenal protection was evident: Systolic Blood Pressure (SBP) decreased significantly from 136.3 to 126.07 mmHg (P < 0.001). Furthermore, the ACR showed a highly significant drop from 120.29 to 78.75 (P < 0.001). Notably, the calculated GFR in this group exhibited a statistically significant acute increase from 97.99 to 102.89 (P = 0.022). Diastolic Blood Pressure (DBP) was the only variable that did not reach statistical significance (P = 0.245) as shown in Table 2.

Table 2.

Metabolic and cardiorenal markers for the females in pre and post intervention (N = 57)

		Pre intervention		Post intervention
Variable	N	Mean	SD	Mean post	SD	P value
weight	57	81.96	10.70	78.18	9.45	< 0.001
BMI	57	26.01	2.73	24.74	2.30	< 0.001
SBP	57	136.3	17.85	126.07	13.09	< 0.001
DBP	57	70.53	9.35	69.39	6.70	0.245
ACR	57	120.29	96.21	78.75	72.88	< 0.001
HbA1c	57	9.28	1.67	7.35	0.90	< 0.001
Cr	57	1.02	0.19	0.93	0.18	< 0.001
calculated GFR	57	97.99	21.66	102.89	25.75	0.022
RBS	57	214.04	78.70	165.00	42.28	< 0.001

*Standard Deviation

The male cohort demonstrated a similarly robust therapeutic response across most variables. Glycemic efficacy was confirmed by the highly significant decrease in HbA1c from 8.87 to 7.29 (P < 0.001) and RBS (mean pre: 200.62 to post: 160.42; P < 0.001). Weight loss was significant, with mean weight dropping from 82.32 to 78.37 kg (P < 0.001). Hemodynamic improvements included a highly significant reduction in SBP (mean pre: 133.2 to post: 124.91; P < 0.001) and a statistically significant reduction in DBP (P = 0.001). Renoprotection was particularly strong, with ACR decreasing highly significantly from 99.56 to 56.07 (P < 0.001). However, unlike the female cohort, the change in calculated GFR for the male sub-group was not statistically significant (mean pre: 94.77 to post: 95.46; P = 0.686), indicating a stable but statistically unchanged filtration rate as shown in Table 3.

Table 3.

Metabolic and cardiorenal markers for the males in pre and post intervention (N = 76)

Variable	N	Pre intervention		Post intervention		p-value
		Mean	SD*	Mean	SD*
Weight	76	82.32	12.04	78.37	10.63	< 0.001
BMI	76	25.94	2.88	24.84	2.58	< 0.001
SBP	76	133.2	16.42	124.91	13.59	< 0.001
DBP	76	71.97	9.26	69.3	5.82	0.001
ACR	76	99.56	90.01	56.07	46.482	< 0.001
HbA1c	76	8.87	1.61	7.29	0.69	< 0.001
Cr	76	1.06	0.18	1.00	0.18	0.001
calculated GFR	76	94.77	23.78	95.46	24.39	0.686
RBS	76	200.62	66.52	160.42	35.55	< 0.001

*Standard Deviation

Discussion

The primary aim of this quasi-experimental study was to evaluate the effect of early intervention in newly diagnosed T2DM with dapagliflozin, the central finding of this study is the significant renoprotective effect, The mean reduction approximately 40%, from 108.44 to 65.79 (P < 0.001) in the ACR within a short three-month window. ACR decrease confirm the drug’s immediate impact on microvascular dysfunction, Importantly, this study contributes to the growing body of literature by focusing specifically on medication-naive, newly diagnosed patients, a cohort often underrepresented in large-scale trials where patients are typically receiving various baseline treatments. This observed 40% mean reduction in ACR is highly consistent with findings from comprehensive systematic reviews of the SGLT2i class, where a pivotal meta-analysis reported an average reduction in the urine ACR of 40.78% in patients with moderately increased albuminuria [25].This strong alignment validates the clinical significance of our results and underscores the drug’s mechanism of action: by inhibiting SGLT2, it corrects glomerular hyperfiltration, a crucial initial step in diabetic kidney disease progression. Mechanistically, this effect is primarily mediated by the restoration of tubuloglomerular feedback (TGF), which in turn reduces the elevated intraglomerular pressure characteristic of early diabetic kidney disease [30, 31].

Furthermore, the stability of serum creatinine levels observed in our study is a crucial safety indicator. This finding is consistent with contemporary expert consensus, which confirms that the initial, mild and reversible decline in eGFR (the “initial dip”) represents a therapeutic effect of correcting hyperfiltration rather than actual kidney harm. This dip is typically small and is not associated with a major acute rise in serum creatinine, supporting the continuation of SGLT2i to achieve long-term kidney function preservation [32]. Our data demonstrates that the renal benefit is already pronounced even before chronic complications fully manifest, supporting a shift toward using SGLT2i as a foundational, protective element in initial T2DM management, potentially altering the long-term disease course.

Comprehensive metabolic and hemodynamic benefits

Beyond the significant renoprotection, the study demonstrated substantial control over systemic metabolic risk factors. Glycemic efficacy was high, with the HbA1c falling dramatically (from 9.043% to 7.314%; P < 0.001), reflecting the potent glucose-lowering capability of dapagliflozin through urinary glucose excretion. Furthermore, the therapy yielded a critical secondary gain: significant body weight reduction from 82.17 kg to 78.29 kg (P < 0.001). This loss of mass is valuable because it acts as an auxiliary factor, independent of the direct glucose-lowering pathway, which positively influences the body’s overall metabolic profile. Specifically, reduced adiposity alleviates insulin resistance and lowers the cardiovascular load. These comprehensive benefits are strongly corroborated by both real-world evidence and major cardiovascular outcomes trials. Retrospective cohort studies evaluating dapagliflozin in routine clinical practice demonstrated significant improvements comparable to our findings, reporting an average HbA1c reduction of approximately 0.9% and a weight reduction of around 2.2 kg over a similar treatment period [33]. When this is coupled with favorable hemodynamic changes, observed reduction in SBP (P < 0.001), The landmark DECLARE-TIMI 58 trial confirmed that this agent reduces SBP significantly (average of 2.4 mmHg) [34, 35]. the treatment offers a powerful, holistic approach to mitigating the multifaceted risks associated with T2DM to provide a comprehensive metabolic and cardiorenal shield that exceeds simple glucose lowering.

Gender-specific observations and calculated GFR

While ACR reduction was robustly significant in both male and female cohorts, an interesting difference was observed in the calculated GFR. The female cohort exhibited a statistically significant acute increase in calculated GFR from 97.99 to 102.89 (P = 0.022), whereas the male cohort showed a stable, non-significant change (mean pre: 94.77 to post: 95.46; P = 0.686). The overall non-significant change for the aggregated population (mean pre: 96.15 to post: 98.64; P = 0.061) is generally interpreted positively, reflecting the immediate stabilization of the hyperfiltrating glomerulus. Nevertheless, this sex-based disparity in initial hemodynamic adjustment warrants deeper mechanistic investigation.

Our findings align with the results of large-scale clinical trials and systematic reviews which consistently confirm the ability of SGLT2i to reduce albuminuria. The magnitude of ACR reduction observed is consistent with prior studies that reported similar declines in patients with comparable baseline levels of albuminuria [25]. This study successfully bridged a local gap by confirming that the well-established benefits of SGLT2i seen in global trials are fully transferable to the patient population in Hebron. The high prevalence of early renal compromise is alarming, as 75% of participants were found to have existing proteinuria at the point of their new diabetes diagnosis. This figure signals an urgent need for proactive screening and educational initiatives within the local healthcare system. The successful shift observed, where the proportion of patients with normal to mildly increased ACR rose to 30% post-treatment, provides crucial, context-specific evidence supporting early therapeutic use of SGLT2i to alter the trajectory of diabetic kidney disease in this region.

Strengths and limitations

The present investigation boasts several key methodological strengths that enhance the reliability and clinical significance of its findings. Foremost among these is the study’s novel focus on medication-naive, newly diagnosed T2DM patients with existing proteinuria, a specific cohort that is often underrepresented but critically important for early intervention strategies. This approach yielded exceptional statistical power through a large and consistent sample size N = 133, which far exceeded the calculated minimum requirement, Furthermore, the briefness of the three-month follow-up period is the most significant constraint; while confirming acute efficacy on surrogate markers ACR, Cr, HBA1C, it is insufficient for drawing conclusions regarding the prevention of long-term CKD progression.

Conclusion

The findings conclusively demonstrate that the early implementation of dapagliflozin 10 mg/day provides powerful, multidimensional protection in newly diagnosed T2DM patients exhibiting proteinuria. The intervention yielded a rapid and definitive therapeutic gain, reducing the critical renal marker ACR. This primary victory was complemented by significant advancements in metabolic risk factor control: Glucose Homeostasis, Body weight, Hemodynamics on Cardiovascular strain, Collectively, these substantial gains across renal, metabolic, and hemodynamic domains validate Dapagliflozin as a crucial agent for providing comprehensive protection and should be readily adopted in initial treatment protocols.

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Abbreviations

ACR

Albumin-to-creatinine ratio

SGLT2i

Sodium-glucose co-transporter 2 inhibitors

DKD

Diabetic kidney disease

DN

Diabetic nephropathy

GFR

Glomerular filtration rate

ESRD

End-stage renal disease

T2DM

Type 2 diabetes mellitus

DM

Diabetes mellitus

HbA1c

Glycated hemoglobin

RBS

Random blood sugar

BMI

Body mass index

BP

Blood pressure

SBP

Systolic blood pressure

DBP

Diastolic blood pressure

Cr

Creatinine

ADA

American diabetes association

WHO

World Health Organization

RAAS

Renin-angiotensin-aldosterone system

Author contributions

Mohammad qabaja conceived the study design, supervised data collection, and contributed to data interpretation and manuscript revision. Shahd Ghrayeb, Seya Arafeh, Siham Natsha, Sara Rabieh contributed to data collection, literature review, and drafting of the manuscript. Beesan maraqa contributed to statistical analysis, and data interpretation. All authors reviewed and approved the final manuscript.

Funding 

This study did not receive any specific grant from any external funding agency. The costs for laboratory tests and medication were covered by the patients themselves as part of their standard, routine clinical care, and the study did not impose any additional financial burden on them.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Human ethics and consent to participate

Informed consent was obtained from all participants, with clearly explained to them the purpose of the study, the potential benefits and risks of participation, the right to withdraw. No identifying information will be collected, and participants will be referred to as codes. They were also reassured that all data collected would remain confidential. Approval was secured from College of Medicine in Hebron University institutional review board (IRB). The consent mandated that any serious or unexpected events would be reported immediately to the IRB.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.