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. 2026 Jul 7;47(8):1357–1365. doi: 10.15537/1658-3175.8828

GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Diabetic Nephropathy: A Comparative Study

Sara Ghadeer Alghadeer a, Sama Sami Kanfar a,*, Zakiah Dheya Algallaf a, Fatimah Mudhar Alfardan a, Rana Alshammrany a, Maha Farhat b, Cyril Cyrus b
PMCID: PMC13360869  PMID: 42445750

Summary

Objective:

To investigate the effects of glucagon-like peptide-1 receptor agonist (GLP-1RAs) on renal function in type 2 diabetes mellitus (T2DM) patients and compared their efficacy to sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in managing diabetic nephropathy.

Methods:

This is a retrospective cohort study conducted at King Fahad University Hospital, including 115 adults (≥18 years) with T2DM and baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2, treated with GLP-1RAs or SGLT-2i for over 1 year. Patients on renal replacement therapy, nephrotoxic drugs, or with incomplete records were excluded. Data were analyzed with Jeffrey's Amazing Statistics Program; the significant value is p < 0.05.

Results:

Participants were treated with either SGLT-2i (67.8%) or GLP-1RAs (32.2%). Both groups showed minimal improvements in glycemic control, hemoglobin A1c decreased from 7.86% to 7.66% (SGLT-2i) and from 8% to 7.76% (GLP-1RAs). Estimated GFR minimally improved by 0.5–1.2 mL/min/1.73m2 (GLP-1RAs) and changed by –1.2 to +10.1 mL/min/1.73m2 (SGLT-2i). Urine albumin/creatinine ratio dropped by 13.35 mg/g with GLP-1RAs but increased by 49.86 mg/g with SGLT-2i.

Conclusions:

Both medications offered comparable glycemic and renal benefits. The GLP-1RAs, however, demonstrated more favorable effects on albuminuria, suggesting potential for superior renal protection in nascent diabetic nephropathy.

Keywords: Diabetic nephropathies, Chronic kidney disease, GLP-1r agonists, SGLT-2 inhibitors

Introduction

A principal cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) is diabetic nephropathy (DN) [1]. It is a major microvascular manifestation type II diabetes mellitus (T2DM), characterized by a gradual deterioration in kidney function, marked by persistent albuminuria and declining estimated glomerular filtration rate (eGFR) [2]. The early stages of DN can present as inconspicuous fatigue, progressing to hypertension and uremic symptoms [3,4]. Risk factors for DN can be modifiable, such as hyperglycemia, hypertension, dyslipidemia, sedentary lifestyle, smoking, and non-modifiable factors such as genetics, ethnicity, early diabetes onset and longer disease duration [5,6]. In Kingdom of Saudi Arabia (KSA), excessive obesity (35.4%) and physical inactivity (58.5%) rates foster the development of DN [7,8]. The current prevalence of DM worldwide is concerning, as 537 million individuals worldwide have diabetes [9]. The incidence of T2DM patients who develop DN is ~10.8% of the global population [10].

Management addresses modifiable risk factors through lifestyle changes to maintain optimal glycemic control and blood pressure, and annual screenings for early detection [11,12]. Pharmacological management includes angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) which are used to reduce microalbuminuria and blood pressure [13,14]. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), complement these therapies by improving glycemic regulation and renal outcomes [15]. The SGLT-2is reduce heart failure risk and preserve eGFR, while GLP-1RAs are effective for weight loss and cardiovascular health [16,17]. Combining these classes provides synergistic benefits [18]. There is a lack of direct comparative trials for renal outcomes between these 2 classes, which limits definitive conclusions about their comparative efficacy in preventing hard renal outcomes [19]. Current guidelines prioritize SGLT2i for eGFR preservation. However, the efficacy of GLP-1RAs in DN remains uncertain and unassessed [20].

This study sought to evaluate the impact of GLP-1RAs on renal-function in patients with T2DM and to compare the benefits of GLP-1RAs versus SGLT2i in the management of DN. The overarching aim was to optimize treatment strategies and enhance patients’ quality of life.

Method

This retrospective cohort study evaluated the effects of GLP-1RAs on renal function markers in patients with T2DM. Data was obtained from the electronic medical records (EMR) of King Fahad University Hospital (KFUH), Al-Khobar, covering the period from May 2023 to February 2025. This study was formulated while adhering to the strengthening the reporting of observational studies in epidemiology (STROBE) guidelines [21]. This study was approved by Institutional Review Board (IRB) at Imam Abdulrahman bin Faisal University, as indicated in the letter numbered IRB-UGS-2024-01-713.

Eligible participants were individuals who had been diagnosed with T2DM, aged ≥18 years, and were being followed up at KFUH. The inclusion criteria were as follows: i) patients who underwent treatment with GLP-1 receptor agonists or SGLT-2 inhibitors for more than 1 year, ii) and had been diagnosed with early-stage DN defined by eGFR ≥60 mL/min/1.73m2. The exclusion criteria included patients who had undergone renal replacement therapy, used nephrotoxic medications, and those with missing data.

A non-probability sampling technique was employed to select patients with T2DM from the KFUH EMR system. A population of 853 patients with T2DM who had been diagnosed with DN was identified. Following the application of predefined exclusion criteria, a final sample of 115 patients was included in the study. Based on the sample size calculator, the minimum required effect size was 76 to detect significant differences in renal biomarkers. The current sample size ensures 89.3% statistical power as per the post-hoc power calculator.

The independent variables were age, sex, nationality, GLP-1 RAs, and SGLT-2i with or without metformin. Other medications included insulin, sitagliptin, atorvastatin, and ACEi. The dependent variables were body mass index (BMI), hemoglobin A1c (HbA1c), fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine, eGFR, urine albumin-creatinine ratio (UACR), urine microalbumin, urine creatinine, liver function tests (LFTs), and lipid profiles.

A predesigned comprehensive data collection sheet and questionnaire to collect relevant data on T2DM patients treated with GLP-1 RA/ SGLT2i for > 1 year. The EMR of KFUH were used to retrieve the baseline characteristics, clinical details, laboratory results, medication, and medical history of the patients with T2DM who had DN.

Laboratory reports for glycemic parameters, renal-function tests, LFTs, and lipid profiles were collected at a minimum of 2 time points, at the beginning of use of medications and after 6 months, to calculate the efficacy of these medications and their effects on the progression of DN. Refinement of the selected patient cohort based on the inclusion/exclusion criteria for improved clarity and relevance to the research objectives. Patients with missing laboratory results were excluded. Stratification of the study cohort based on eGFR calculated using the Chronic kidney disease epidemiology collaboration (CKD-EPI) 2009 and the Modification of diet in renal disease (MDRD) study equations.

Statistical analysis

The Jeffrey's amazing statistics program (JASP) software was used to analyze data. The JASP (version 0.19.0), and a p < 0.05 indicated a statistically significant difference. The descriptive statistics are presented using numbers, percentages, and mean and standard deviation. Statistical normality was measured using the Shapiro-Wilk test, and heterogeneity tests were applied. For between-group comparisons, a Student's t-test was used where appropriate, and the Mann-Whitney U test and Kruskal-Wallis test were applied as non-parametric tests.

Results

The present study compared the effects of GLP-1RAs and SGLT-2i on the progression of DN. A comparison of the sociodemographic parameters between the SGLT-2 and GLP-1 medication groups is presented in (Table 1). Out of 115 participants, (n = 78) 67.8% were on SGLT-2i, and (n = 37) 32.2% were on GLP-1RAs. The mean age of the patients was significantly higher in the SGLT-2 group (62.26±10.83 years) compared to the GLP-1 group (53.32±11.34 years), with a p < 0.001. As regards sex distribution, there was a higher number of males and females in the SGLT-2 group (n = 41, 70.7% and n = 37, 64.9%, respectively) compared to the GLP-1 group (n = 17, 29.3% and n = 20, 35.1%). However, the difference was not statistically significant (p = 0.507). In addition, the mean BMI was slightly higher in the SGLT-2 group (34.65±7.97 kg/m2) than in the GLP-1 group (32.64±5.67kg/m2); however, no statistically significant differences were observed for BMI (p = 0.938) or weight (p = 0.881) between the 2 groups. As regards medication, the most commonly prescribed drug was dapagliflozin (n = 78, 67.8%) and dulaglutide (n = 29, 25.2%), with fewer patients on semaglutide (n = 6, 5.2%) or a combination of semaglutide and dulaglutide (n=2, 1.7%) (Fig. 1A). As regards the additional prescribed medications in the participants overall, metformin was the most common (79.1%), followed by atorvastatin (68.7%) and sitagliptin (50.4%). Insulin was used by 36.5% of the participants, while only 7.8% taking an ACEi (lisinopril). Notably, the SGLT-2 group had a higher percentage of patients using metformin, sitagliptin, atorvastatin, and ACEi than the GLP-1 group (Fig. 1B).

Table 1.

Sociodemographic parameters between the 2 medication groups.

Medication Group
Variables SGLT-2 Mean (SD) GLP-1 Mean (SD) P - Values
Age (Years) 62.26 (10.83) 53.32 (11.34) <0.001
Gender (n, %) 0.507
  Female 37 (64.9%) 20 (35.1%)
  Male 41 (70.7%) 17 (29.3%)
Height (cm) 160.74 (10.97) 163.33 (9.32) 0.321
Weight (kg) 82.31 (22.69) 81.36 (16.98) 0.881
BMI (kg/m2) 34.65 (7.97) 32.64 (5.67) 0.938
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SGLT-2: Sodium-glucose cotransporter 2, GLP-1: Glucagon-like peptide-1, SD: Standard deviation, CM: Centimeter, KG: Kilogram, BMI: Body mass index, N: Total number.

Fig. 1.

Fig. 1.

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Frequencies distribution of medication and types: (A) SGLT-2 and GLP-1 classes and (B) other medications used by participants. SGLT-2: Sodium-glucose cotransporter 2, GLP-1: Glucagon-like peptide-1, n: Total number.

After 6 months, both medication groups demonstrated slight improvements in glycemic control, although neither difference reached statistical significance (Table 2). Numerically, the FBG in the SGLT-2 group decreased by ~4 mg/dL, whereas in the GLP-1 group, it decreased by only ~1 mg/dL. On the other hand, improvements in the HbA1c levels were marginally more pronounced in the GLP-1 group, decreasing by 0.24% compared to a 0.20% decrease in the SGLT-2 group. A comparison of the efficacy of different drug therapies of GLP-1RA and SGLT-2i medication classes on glycemic parameters, HbA1c, and FBG is illustrated in Fig. 2.

Table 2.

Comparison of hyperglycemic, RFTs, UACR, lipid profiles and LFTs parameters of diabetic patients between the 2 medication groups over a period of 6 months.

Labs values, Mean (SD)
Medication Group At baseline After 6 months P - values
Glycemic Index
  182.5ptHbA1c (%) GLP-1 8.00 (1.85) 7.76 (1.74) 0.109
SGLT-2 7.86 (1.54) 7.66 (1.38) 0.089
  FBG (mg/dL) GLP-1 145.03 (46.41) 144.19 (60.14) 0.241
SGLT-2 144.83 (48.14) 144.83 (48.14) 0.468
RFTs
  182.5ptBUN (mg/dL) GLP-1 13.43 (7.55) 13.54 (8.59) 0.861
SGLT-2 15.31 (5.40) 16.03 (6.78) 0.168
  Serum Creatinine (mg/dL) GLP-1 0.88 (0.43) 0.87 (0.40) 0.806
SGLT-2 0.91 (0.30) 0.98 (0.51) 0.125
  eGFR (mL/min/1.73m2) by CKD-EPI equation GLP-1 121.6 (79,6) 122.1 (66.3) 0.44
SGLT-2 113.37 (34.0) 123.48 (71.5) 0.068
  eGFR (mL/min/1.73m2) by MDRD equation GLP-1 86.5 (19.6) 87.7 (22.5) 0.269
SGLT-2 80.1 (20.6) 78.3 (22.8) 0.084
UACR
  UACR (mg/g) GLP-1 53.94 (92.89) 40.59 (66.26) 0.576
SGLT-2 154.36 (337.9) 204.22 (472.4) 0.208
  Urine Creatinine (mg/dL) GLP-1 133.18 (76.60) 114.91 (65.08) 0.141
SGLT-2 97.58 (60.68) 84.72 (47.38) 0.03
  Urine Microalbumin (mg/dL) GLP-1 19.22 (45.92) 13.31 (45.87) 0.242
SGLT-2 13.10 (35.35) 14.35 (30.41) 0.932
Lipid profile
  Cholesterol (mg/dL) GLP-1 179.14(50.55) 163.62(42.82) 0.008
SGLT-2 159.82(45.74) 151.94(38.00) 0.029
  HDL (mg/dL) GLP-1 47.22(12.42) 46.27(12.41) 0.304
SGLT-2 44.97(12.68) 43.79(10.95) 0.209
  LDL (mg/dL) GLP-1 107.35(45.90) 98.46(39.70) 0.152
SGLT-2 93.95(40.61) 86.99(34.68) 0.024
  Triglycerides (mg/dL) GLP-1 147.76(129.86) 124.65(63.42) 0.044
SGLT-2 117.21(65.27) 114.44(59.04) 0.635
LFTs
  Albumin (g/dL) GLP-1 4.29(0.35) 4.45(0.32) <0.001
SGLT-2 4.22(0.39) 4.36(0.42) <0.001
  Total Protein (g/dL) GLP-1 7.15(0.67) 7.22(0.46) 0.42
SGLT-2 7.12(0.50) 7.14(0.49) 0.9
  ALT (U/L) GLP-1 24.73(8.19) 23.49(10.20) 0.385
SGLT-2 20.10(10.70) 22.03(16.41) 0.158
  ALP (U/L) GLP-1 85.41(25.89) 88.27(25.06) 0.683
SGLT-2 82.91(32.19) 88.03(32.61) 0.007
  AST (U/L) GLP-1 21.51(7.79) 26.00(34.29) 0.432
SGLT-2 18.49(7.65) 21.00(11.92) 0.007
  LDH (U/L) GLP-1 175.95(51.40) 162.16(32.34) 0.016
SGLT-2 167.60(48.44) 159.17(35.76) 0.041
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SD: standard deviation, SGLT-2: sodium-glucose cotransporter 2, GLP-1: glucagon-like peptide-1, RFT: renal function test, UACR: urine albumin-to-creatinine ratio, LFT: liver function test, HbA1c: hemoglobin A1c, FBG: fasting blood glucose, BUN: blood urea nitrogen, eGFR: estimated glomerular filtration rate, CKD-EPI: chronic kidney disease epidemiology collaboration, MDRD: modification of diet in renal disease, HDL: high density lipoprotein, LDL: low density lipoprotein, ALT: alanine aminotransferase, ALP: alkaline phosphatase, AST: aspartate aminotransferase, LDH: lactate dehydrogenase, U/L: units per liter, g/dL: grams per deciliter, mg/dL: milligrams per deciliter, mL/min: milliliter per minute.

Fig. 2.

Fig. 2.

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Comparison of FBG (mg/dL) and HbA1c (%) between the 2 groups of patients treated with different drugs. FBG: Fasting blood glucose, HBA1c: Hemoglobin A1c.

The changes in renal function tests (RFTs) and UACR at baseline and after 6 months in the 2 medication groups are presented in Table 3. Both groups exhibited minimal changes in BUN and serum creatinine levels. The MDRD-based eGFR decreased by 1.8 mL/min/1.73m2 in the SGLT-2 group, whereas this improved in the GLP-1 group by 1.2 mL/min/1.73m2, however, both groups exhibited an improvement in eGFR determined using the CKD-EPI equation with 0.5, and 10.1 mL/min/1.73m2 in the GLP-1 (p = 0.440) and SGLT-1 (p = 0.068) groups. Additionally, the UACR increased in the SGLT-2 group by 49.86 mg/g, whereas it decreased by 13.35 mg/g in the GLP-1 group. Urine creatinine levels decreased in both groups, with a significant reduction in the SGLT-2i group (p = 0.03). Fig. 3 illustrates the comparison of renal function parameters—BUN, eGFR, and UACR levels—at baseline and following 6 months of treatment across the individual drug therapies.

Table 3.

Comparison of metabolic, renal, hepatic and lipid profile changes between the 2 medication groups.

Medication group
GLP-1 Mean difference (SD) SGLT-2 Mean difference (SD) P - values
HbA1c (%) –0.2 (1.2) –0.2 (1.3) 0.9
FBG (mg/dL) –0.8 (62.5) –4.3 (53.9) 0.6
RFTs
  BUN (mg/dL) 0.1 (3.7) 0.7 (4.6) 0.6
  Serum Creatinine (mg/dL) –0.0059 (0.1) 0.064 (0.4) 0.1
  eGFR (mL/min/1.73m2) based on CKD-EPI equation 0.5 (18.9) 10.1 (59.1) 0.7
  eGFR (mL/min/1.73m2) based on MDRD equation 1.2 (11.7) –1.8 (11.4) 0.3
  UACR (mg/g) –13.35 (91.4) 49.86 (254.7) 0.2
  Urine Creatinine (mg/dL) –20.3 (63.7) –14.7 (58) 0.9
  Urine Microalbumin (mg/dL) –3.3 (12.1) –0.4 (26.0) 0.4
Lipid profile
  Cholesterol (mg/dL) –15.5 (33.5) –7.9 (31.3) 0.4
  HDL (mg/dL) –0.9 (5.1) –1.2 (8.2) 0.5
  LDL (mg/dL) –8.9 (37) –7 (27.8) 0.8
  Triglycerides (mg/dL) –23.1 (79.9) –2.8 (51.4) 0.3
LFTs
  Albumin (g/dL) 0.2 (0.3) 0.1 (0.3) 0.6
  Total Protein (g/dL) 0.070 (0.5) 0.019 (0.3) 0.7
  ALT (U/L) –1.2 (9.9) 1.9 (11.9) 0.1
  ALP (U/L) 4.5 (34.3) 2.5 (8) 0.4
  AST (U/L) 2.9 (19.6) 5.1 (16.9) 0.5
  LDH (U/L) –13.8 (33.1) –8.4 (42.3) 0.5
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Mean changes, whether positive or negative (expressed with +\–), p - value indicates whether the mean changes were statistically significant between the 2 classes. SGLT-2: sodium-glucose cotransporter 2, GLP-1: glucagon-like peptide-1, RFT: renal function test, UACR: urine albumin-to-creatinine ratio, LFT: liver function test, HbA1c: hemoglobin A1c, FBG: fasting blood glucose, BUN: blood urea nitrogen, eGFR: estimated glomerular filtration rate, CKD-EPI: chronic kidney disease epidemiology collaboration, MDRD: modification of diet in renal disease, HDL: high density lipoprotein, LDL: low density lipoprotein, ALT: alanine aminotransferase, ALP: alkaline phosphatase, AST: aspartate aminotransferase, LDH: lactate dehydrogenase, U/L: units per liter, g/dL: grams per deciliter, mg/dL: milligrams per deciliter, mL/min: milliliter per minute.

Fig. 3.

Fig. 3.

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Comparison of renal parameters between the 2 groups treated with different drugs. (A) BUN (mg/dL), (B) eGFR determined using the CKD-EPI Equation and (C) UACR. BUN: blood urea nitrogen, eGFR: Estimated glomerular filtration rate, CKD-EPI: Chronic kidney disease epidemiology collaboration.

The changes in lipid profiles and LFTs among patients on GLP-1RA or SGLT-2i are presented in Table 2. With regards to lipid profiles, both groups exhibited significantly reduced cholesterol levels (179.14 to 163.62 mg/dL, 159.82 to 151.94 mg/dL) for the GLP-1 (p = 0.008) and SGLT-2 (p = 0.029) groups. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels were reduced with both medications, significantly reducing LDL with SGLT-2i (p = 0.024) and triglycerides with GLP-1RA (p = 0.044). As regards LFTs, albumin was significantly increased in the 2 medication groups (p < 0.001). Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels increased in both groups, although only the difference in the SGLT-2 group reached statistical significance. Additionally, there was a significant decrease in LDH levels by -8.43 U/L in SGLT-2 and -13.79 U/L in the GLP-1 group. Overall, both therapies modestly improved lipid and liver parameters.

When comparing both medication classes across all parameters of metabolic, renal, hepatic and lipid profiles, there were differences in efficacy. However, these differences were not statistically significant. The differences between laboratory value means at baseline and after 6 months, and the respective p - values are presented in Table 3.

Discussion

This study sought to evaluate the impact of GLP-1RAs on renal-function markers in individuals with T2DM and to compare their efficacy with SGLT-2 in the management of DN, by analyzing changes in metabolic, renal, hepatic and lipid profiles over a period of 6 months. The glycemic control profiles of SGLT2i and GLP-1RA demonstrated steady improvements in HbA1c and FBG levels, aligning with established findings from the literature and clinical trials that consistently validate both drug classes as reliable options for the management of glycemia [15,22]. In the present study, however, the observed improvement margins were minimal, likely due to the selected study population. All patients were already undergoing treatment with their respective medications and had controlled HbA1c and FBG levels, as noted in Table 2. Furthermore, the improvement margins between the 2 classes, as detailed in Table 2, were markedly similar, rendering it difficult to conclude the superiority of 1 class over the other. Notably, GLP-1RAs achieved these improvements as monotherapy, whereas SGLT2is were more frequently prescribed alongside other medications, such as metformin, sitagliptin and atorvastatin, as illustrated (Fig. 1A). This distinction underscores the versatility of GLP-1RAs in monotherapy settings, aligning with the findings from the study by Yu et al [23] who highlighted GLP-1RAs as a promising therapeutic option, providing not only effective glycemic control, but also protective cardiorenal benefits.

The analysis of renal-function parameters, as presented in Table 3, revealed minimal improvements in eGFR, BUN and serum creatinine levels for both medication classes. Using the MDRD equation, eGFR exhibited contrasting trends: a slight decline of –1.8 mL/min/1.73m2 in the SGLT2 group, compared to a modest improvement of +1.2 mL/min/1.73m2 in the GLP-1RA group. This aligns with the findings in the systematic review by Chen et al [24]. However, when eGFR was calculated using the CKD-EPI 2009 equation, both groups demonstrated improvements, highlighting discrepancies between the formulas. These findings underscore the limitations of the MDRD equation, which is known to underestimate eGFR at higher values (>60 mL/min/1.73m2), leading to the misclassification of CKD stages and overestimating disease prevalence. Although CKD-EPI and MDRD equations are widely used for calculating eGFR, CKD-EPI has consistently proven to be more accurate, particularly when assessing higher GFR levels in elderly populations and diverse demographic groups. Earlier studies conducted in KSA further support CKD-EPI, and the improvement in eGFR aligns with these findings [25,26].

Noteworthy differences between UACR levels in the 2 medication groups were observed, as shown in Table 3. GLP-1RAs improved the microalbumin-to-creatinine ratio (–13.35 mg/g mg/mmol), whereas SGLT2i led to a deterioration (+49.86 mg/g). This suggests that GLP-1RAs may provide superior protection against albuminuria, consistent with findings from previous trials attributing this benefit to the effects of GLP-1 on macroalbuminuria [27]. However, the worsening microalbumin-to-creatinine ratio observed with the use of SGLT2i contradicts the results of previous trials, such as CREDENCE and EMPA-REG, which demonstrated improvements in microalbuminuria and broader renal benefits, particularly in preserving eGFR [28,29]. It is important to note that not all laboratory results for the microalbumin-to-creatinine ratio were available after 6 months, potentially limiting the ability to capture the maximum therapeutic effects of these medications. Additionally, urine creatinine levels decreased significantly in both groups, with a more pronounced reduction observed in the SGLT-2 group (p = 0.03), highlighting its potential impact on renal function.

The ACEi and ARBs were underutilized, accounting for only 7.8%, as displayed in Fig. 1. This may be attributed to the selection criteria of patients with an eGFR>60 mL/min/1.73m2, which excluded those with more advanced renal impairment who typically benefit the most from these medications. This highlights the potential viability of GLP-1RAs and SGLT2i as monotherapy options for patients intolerant to ACEi or ARBs, this outcome is supported by Zhou et al [30].

When comparing lipid profiles, both GLP-1RAs and SGLT2i depicted general improvements; however, GLP-1RAs exhibited a statistically significant advantage in reducing triglyceride and LDL levels, while both classes exerted significant lowering effects on total cholesterol levels. These findings align with those in the study by Su et al [31], who demonstrated the beneficial impact of GLP-1RAs on lipid profiles. Despite this, both drug classes exhibited overall positive effects on lipid parameters; this differs from the findings of the study by Garcia et al [32], who reported that SGLT2is had a slight triglyceride-lowering effect, but were associated with increased cholesterol levels, suggesting a potentially negative impact of SGLT2is on cholesterol. However, that effect was compensated in the present study cohort due to additional medications.

The GLP-1RAs and SGLT2i both led to modest improvements in liver function parameters. While both classes contributed to improved LDH levels, GLP-1RAs led to statistically significant (0.016) differences in the present study. These results are consistent with previous meta-analysis demonstrating that both drug classes positively affect liver enzyme and metabolic profiles in patients with conditions, such as Non-alcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) [33,34]. Both classes appear to be reasonably safe for patients with early-stage DN in the short term, based on the reported stability in renal function and slight improvements in metabolic parameters. These findings add to the existing body of evidence by demonstrating these results in a real-world setting and highlighting that either class of medication can be used without substantially impairing renal function [35].

The high prevalence of obesity, a characteristic of T2DM, is revealed by the demographic analysis of the present study. Both groups were classified as obese, with mean BMI values of 34.65 ± 17.97 kg/m2 for the SGLT-2 group and 32.64 ± 5.67 kg/m2 for the GLP-1RA group, as shown in Table 1. Recent studies have demonstrated that drugs, such as dual GIP/GLP-1RA (tirzepatide) and GLP-1RA (semaglutide) can effectively manage blood sugar levels and reduce body weight in obese diabetic populations [36,37].

Although the present study provides insightful information about the relative effects of SGLT2i and GLP-1RAs on renal function and metabolic parameters in diabetics, few limitations need to be addressed. As the data were derived from a single medical facility, the findings cannot be applied to the greater Saudi Arabian diabetes population. Furthermore, the statistical power to detect significant differences were likely limited by the relatively small sample size, which was mostly caused by the lack of patients with 2 pertinent laboratory tests separated by at least 6 months. Another drawback is that the follow-up times of participants varied from 6 months to 1 year, which may have had an impact on the precision and consistency of assessments of the treatment outcomes. In order to overcome these drawbacks, future research is required to include larger, more varied patient groups from different Saudi Arabian healthcare facilities, guaranteeing consistent time between laboratory tests and prolonging the follow-up period. The long-term Reno protective effects of GLP-1RAs and SGLT2i also need to be clarified by combining randomized controlled trial (RCT) methodologies and classifying patients according to their baseline renal function. This will provide more accurate information on which patient subgroups benefit the most from each treatment.

In conclusion, the study investigated the impact of GLP-1RA and SGLT-2i on the management of DN. Both therapies resulted in a modest improvement in blood sugar control. Notably, GLP-1RAs were more effective than SGLT-2 inhibitors at lowering albuminuria. Both treatment groups experienced comparable improvements in lipid profiles, eGFR, and liver function. Although nausea and vomiting were more common with the use of SGLT-2is, both medication classes were typically well tolerated. These findings suggest that GLP-1 receptor agonists and SGLT-2 inhibitors are both safe and effective therapeutic options for diabetic kidney impairment in its early phases. However, GLP-1 therapy, particularly when used in combination therapy, may provide improved renal protection, as indicated by increased eGFR and decreased albuminuria.

Disclosure statement

No AI tools were utilized in the writing of the article, creation of images, collection, and analysis of data. We hereby confirm that the article titled has not been previously published in any preprint servers.

Acknowledgement

We would like to thank Spandidos Publications (www.https://www.spandidos-publications.com/languageediting) for the English language editing.

Disclosure

The authors declare no conflict of interest. This research was not supported or funded by any pharmaceutical or medical device company. Imam Abdulrahman bin Faisal University Institutional Review Board (IRB) granted ethical approval, as indicated in the letter numbered IRB-UGS-2024-01-713, dated 10/10/2024.

Contributor Information

Sara Ghadeer Alghadeer, Email: Sgmamk@gmail.com.

Sama Sami Kanfar, Email: Kanfarsama@gmail.com.

Zakiah Dheya Algallaf, Email: Zakiah.dh@gmail.com.

Fatimah Mudhar Alfardan, Email: Fatimahalfardan@gmail.com.

Rana Alshammrany, Email: ranahamoudalshamrani@gmail.com.

Maha Farhat, Email: mFarhat@iau.edu.sa.

Cyril Cyrus, Email: ccyrus@iau.edu.sa.

References

Articles from Saudi Medical Journal are provided here courtesy of Saudi Medical Journal

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