Original Article

Volume 000, Number 000, May 2025, pages 000-000

The BRIDGE-DS Study: Improved Glycemic Control and Renal Function in Type 2 Diabetes Mellitus Patients Using the Fixed-Dose Combination of Dapagliflozin and Sitagliptin

CKD is marked by either intermittent or continuous albuminuria and/or a gradual decrease in the glomerular filtration rate (GFR) [1]. Over 40-50% of patients with diabetes may develop CKD, potentially leading to end-stage kidney disease (ESRD), which requires dialysis or transplantation [1]. It is a significant global health challenge, affecting 20-40% of individuals with diabetes [2].

India, China, and the United States are among the top three countries worldwide with the highest burden of CKD [3]. A systematic review investigating CKD prevalence in South Asia revealed a pooled prevalence of 10.2% among Indian adults (ranging from 4.2% to 21%) [4].

Patients with type 2 diabetes mellitus (T2DM) and poor glycemic control are at higher risk of developing CKD [5]. A cross-sectional study investigating the association between glycated hemoglobin (HbA_1c) levels, CKD, and cardiovascular disease (CVD) found that every 1% increase in HbA_1c was associated with a 30-40% higher rate of CKD or CVD [6]. In a prospective observational study, researchers found that every 1% reduction in mean HbA_1c was associated with a 21% reduction in T2DM-related deaths, a 14% reduction in the risk of myocardial infarction, and a 37% reduction in the risk of developing microvascular complications, all with highly significant P-values (P < 0.0001) [7].

CKD is highly prevalent in patients with T2DM for 15 years or more, as well as those with hypertension, hyperlipidemia, and diabetic retinopathy [8]. CKD exacerbates health outcomes, increasing hospitalization risk and deteriorating the quality of life [2]. It exerts a significant economic burden on patients due to the high costs of treatment, including dialysis and transplantation, and the associated healthcare expenditures for managing complications [9]. CKD imposes various restrictions on daily life, affecting patients both physically and mentally, even in the early stages. Patients with CKD have poor health-related quality of life, which worsens as the disease progresses to ESRD [10].

Risk assessment and early identification can help optimize care and prevention strategies for CKD among individuals with diabetes [5, 11]. A comprehensive understanding of available treatments, particularly glucose-lowering medications, is of paramount importance for effectively managing CKD. Metformin can be given to individuals with T2DM and CKD (estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m²) [12]. The ambiguity surrounding the use of metformin in those with advanced CKD is due to the perceived risk of metformin-associated lactic acidosis [13]. In cases where metformin is contraindicated or not tolerated, or in patients with elevated HbA_1c levels unresponsive to metformin, dipeptidyl peptidase-4 inhibitors (DPP4is) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2is) offer promising alternatives [14].

SGLT2is and DPP4is have emerged as promising therapies for CKD without an increased risk of hypoglycemia [15]. Dapagliflozin, an SGLT2i, reduces glucose reabsorption in the kidney’s proximal tubule, showing efficacy in preventing kidney failure and prolonging survival in CKD patients, regardless of diabetes status [16]. The DECLARE-TIMI 58 trial demonstrated that dapagliflozin effectively prevents and slows CKD progression in patients with T2DM [17]. SGLT2is not only reduce the risk of ESRD but also cardiovascular death and/or hospitalization for heart failure independent of their glucose-lowering effects [18]. A systematic review revealed that DPP4is preserve eGFR and reduce the albumin-to-creatinine ratio in patients with T2DM [19]. Sitagliptin, a DPP4i, boosts insulin secretion and reduces glucagon release [20]. However, sitagliptin is eliminated from the body through the kidneys, and it is important to consider dose adjustments for patients with moderate or severe CKD or those with ESRD on dialysis [21, 22].

The notable benefits of combining dapagliflozin and sitagliptin (D/S) for managing T2DM may lead to optimized treatment strategies and improved patient outcomes within the Indian healthcare landscape. Together, they provide synergistic effects, improving glycemic control beyond monotherapy. This dual approach addresses multiple aspects of glucose regulation simultaneously, potentially leading to more comprehensive control, as shown in several clinical trials [23]. A systematic review conducted to compare the renal outcomes associated with pharmacotherapy administered to patients diagnosed with T2DM reported renoprotective effects for medications like SGLT2is and DPP4is, including slowing the decline of GFR and reducing both albuminuria and renal adverse events (AEs) [24]. This fixed-dose combination (FDC) was approved in India in 2022 [25].

The BRIDGE-DS study assessed the effectiveness and safety of FDC D/S in Indian T2DM patients with CKD. The objectives were: 1) to assess the changes in key clinical parameters, such as HbA_1c, fasting plasma glucose (FPG), postprandial glucose (PPG), serum creatinine, and eGFR following the administration of FDC D/S; 2) to determine the safety profile of FDC D/S in T2DM patients with varying stages of CKD; and 3) to assess the impact of FDC D/S on CKD progression in T2DM patients across different CKD stages.

The choice of this specific FDC D/S was supported by its unique combination targeting complementary pathways, established individual effectiveness and safety profiles, and clinical relevance to diabetes patients with CKD. Regulatory approval and availability further endorsed its suitability for evaluation in this study.

A retrospective, multicenter, observational, case-based questionnaire survey was conducted to collect data anonymously from diabetologists and endocrinologists practicing in various locations in India. This multicenter study included data from T2DM patients with CKD from different hospitals and diabetes clinics.

The study included patients with T2DM and CKD who received FDC D/S (dapagliflozin 10 mg/sitagliptin 100 mg). The inclusion and exclusion criteria are listed below.

Inclusion criteria were: 1) both male and female patients, > 18 years of age, diagnosed with T2DM and CKD with eGFR in the range of 15 - 90 mL/min/1.73 m²; and 2) patients who received FDC D/S.

Exclusion criteria were: 1) patients with diabetes below the age of 18 years; 2) individuals who did not have CKD; 3) patients who did not receive an FDC D/S combination; 4) pregnant individuals with T2DM; 5) patients with ESRD; and 6) patients intolerant to either dapagliflozin or sitagliptin.

Data from 510 patients were collected from clinicians using digitalized case report forms (CRFs) over a 7-month period, from September 2023 to April 2024.

Statistical analyses were conducted using the SPSS^® Version 23.0 software. Median and interquartile ranges (IQRs) for variables before and after the use of FDC D/S were calculated.

Approval from the Institutional Review Board (IRB) was obtained from the primary study site. Data were collected anonymously from the study participants. All information was kept confidential using codes and document locking through login details. This study was conducted in compliance with the ethical standards of the responsible institution on human subjects as well as with the Helsinki Declaration.

The study included 510 patients with a median age of 56 years (IQR: 49 - 64 years). Of these, 67.6% (N = 345) were male and 32.4% (N = 165) were female. The medical history of the patients included diuretic use, dyslipidemia, physical inactivity, prior history of CVD, smoking, and use of medications like statins, the details of which are summarized in Table 1.

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Table 1. Medical History of the Patient

The reasons for adding D/S to these patients’ therapeutic regimens are listed in Table 2.

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Table 2. Reasons for the Addition of FDC D/S to the Patients’ Therapeutic Regimen

CKD progression in terms of eGFR is summarized in Table 3 [26], while Table 4 [26] summarizes CKD progression by albuminuria.

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Table 3. CKD Progression by eGFR [26]

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Table 4. CKD Progression by Albuminuria [26]

Table 5 presents a pairwise comparison of variables before and after treatment with FDC D/S for 3 months. The median HbA_1c level significantly decreased from 9.00% to 7.50% after treatment with FDC D/S, indicating improved glycemic control (P < 0.001). All other variables showed significant P-values (< 0.05).

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Table 5. Effect on Various Parameters After Treatment With FDC D/S

AEs that occurred during the treatment are illustrated in Table 6.

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Table 6. AEs During FDC D/S Use

The most common AEs observed were urinary tract infections (UTIs) (24.51% of patients), dehydration (15.88% of patients), hypoglycemia (10.20% of patients), and genital mycotic infection (7.65% of patients). Other AEs included changes in serum uric acid, a decrease in renal creatinine clearance, diabetic ketoacidosis, hypotension, vulvovaginitis, and hypovolemia. Sitagliptin dose adjustments are recommended for individuals with moderate-to-severe CKD or ESRD; however, it was not adjusted in our study. Of note, no specific increase in AEs was observed in these participants (n = 41/510).

CKD secondary to diabetes poses a significant global health challenge, affecting up to 40% of individuals with diabetes, with India bearing a substantial burden of the disease [3].

Previous studies have identified various risk factors associated with CKD in patients with T2DM. A cross-sectional study evaluated the risk factors for CKD, including older age, lower body mass index (BMI), smoking habits, albuminuria, hypertension, CVD, duration of diabetes, HbA_1c, dyslipidemia, and medications (diuretics, antiplatelets, antihypertensives), among others [5]. This study showed that the highest CKD prevalence rates were found in individuals aged over 75 years and those with an HbA_1c of 8% or higher [5]. Another study on patients with stages 3-5 CKD (n = 3,303) showed that varying lipid profiles had an independent association with renal replacement therapy and rapid CKD progression [12]. Individuals with a history of smoking had significantly higher eGFR and hemoglobin levels [27]. While metformin is a common therapy, several therapeutic approaches for CKD, including FDCs, have been explored.

Mechanisms via which SGLT2is and DPP4is lower blood glucose levels are as follows.

SGLT2is have been found to significantly reduce the risk of acute kidney injury (AKI) by 36-60%, despite being associated with higher incidences of AEs related to hypovolemia [28]. A systematic review and meta-analysis consisting 50,820 participants showed that although SGLT2is are associated with a heightened risk of genital infections (risk ratio (RR) of 3.30 (95% confidence interval (CI): 2.74 - 3.99)), there were no significant differences between the SGLT2i group and the control group [29]. These findings highlight the importance of weighing the benefits of renal protection against the risk of AEs when considering SGLT2i therapy in patients with CKD. The DAPA-CKD trial also showed that the use of dapagliflozin (versus a placebo) was associated with minimal kidney and cardiovascular AEs, and that there were no significant differences between groups having participants with and without CVD. The study demonstrated, however, that dapagliflozin usage was associated with a reduced risk of kidney failure (hazard ratio (HR) 0.61, 95% CI: 0.48 - 0.78) [16]. The landmark DECLARE-TIMI 58 trial further supports the renal benefits of SGLT2is. This study followed up on patients with T2DM over a median period of 4.2 years. Those treated with dapagliflozin (46%) experienced a notable decrease in the rate of decline of eGFR to less than 60 mL/min per 1.73 m² (by at least 40%) compared to the placebo group. Moreover, the incidence of severe renal complications such as ERSD/renal death was significantly lower in those receiving dapagliflozin compared to those receiving a placebo (P = 0.012). These results highlight the potential of SGLT2is in improving renal outcomes independent of cardiovascular status [17].

The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease suggests using SGLT2is for individuals with T2DM, CKD, and an eGFR of ≥ 20 mL/min/1.73 m² and continuing when eGFR falls below 20 mL/min/1.73 m², unless not tolerated by the patient [30]. In line with the American Diabetes Association (ADA) Standards of Care in Diabetes 2024, SGLT2is are indicated for reducing CKD progression and cardiovascular events in individuals with T2DM, an eGFR of ≥ 20 mL/min/1.73 m², and urinary albumin of ≥ 200 mg/g creatinine [12, 18]. These recommendations emphasize the growing recognition of SGLT2is as valuable therapeutic agents for CKD management in T2DM patients.

DPP4is represent another class of antidiabetic agents with potential benefits in patients with CKD. In a prospective study, T2DM patients (N = 49) with renal dysfunction switched from other DPP4is (vildagliptin, linagliptin, or alogliptin) to a low dose of sitagliptin based on their renal function. Results showed stable renal function and glycemic control with no AEs [31]. The TECOS study involving individuals with CKD showed that sitagliptin was generally well tolerated by CKD patients (at a median follow-up period of 2.8 years) [32]. These studies suggest that low-dose sitagliptin, adjusted to renal function, is a safe and effective option for treating T2DM patients with CKD.

The combination of SGLT2is and DPP4is offers a synergistic approach to T2DM management, as demonstrated in this study and supported by previous research. At the same time, SGLT2is enhance the effects of DPP4is by improving beta-cell function and insulin sensitivity [33]. This combination decreases glycemic variability, reduces the risk of hypoglycemia, and offers cardiovascular and renal protection in patients with T2DM [34]. Additional benefits include once-daily dosing that improves adherence and accelerates the attainment of target HbA_1c levels, offering enhanced glycemic control with a simplified regimen [14].

Patient profiles considered suitable for FDC D/S include: 1) patients with uncontrolled glycemic parameters; 2) elderly patients; 3) those at high risk of CVD; 4) those with T2DM and heart failure (HF); 5) those with T2DM and atherosclerotic cardiovascular disease (ASCVD); 6) T2DM patients with CKD; and 7) individuals at high risk of hypoglycemia [34].

In the retrospective Real DAPSI study, 358 patients with T2DM were treated with FDC D/S. After 12 weeks, significant reductions in mean HbA_1c levels (from 8.9% to 7.2%), mean fasting blood glucose levels (from 178.8 to 124.0 mg/dL), and PPG levels (from 273.9 to 176.0 mg/dL) were observed. Of note, no serious AEs were reported, thus proving that this combination was effective and safe in managing T2DM [23]. Furthermore, a systemic review by Li et al in patients with T2DM (n = 4,828) revealed that compared to using DPP4is alone, the combination therapy not only improved glycemic control but also led to a significant reduction in body weight (by 2.05 kg) and systolic blood pressure (by 5.90 mm Hg). The combination reduced HbA_1c levels by 0.31%, FPG by 8.94 mg/dL, triglyceride levels by 3.25%, and total cholesterol levels by 1.48% [33]. Interestingly, even low doses of SGLT2is in the combination exhibited comparable or superior efficacy in some aspects compared to high doses of monotherapy [33].

Contraindications of FDC D/S include [34]: 1) individuals with eGFR of < 45 mL/min/1.73 m²; 2) individuals with a history of diabetic ketoacidosis; and 3) individuals with a history of pancreatitis.

A study by Li et al showed that AEs were generally similar between the combination therapy and when each drug was used alone, except for an increased risk of genital infections with the combination as compared to DPP4is alone (RR = 5.31) and a consistent risk of genital infections compared to SGLT2is alone (RR = 0.61) [33]. In individuals receiving SGLT2is, dehydration or orthostatic hypotension resulting from volume reduction due to osmotic diuresis and natriuresis may also be a potential concern, although these AEs have been infrequently documented in randomized controlled trials [35]. In addition, the TECOS study showed that within the CKD cohort, when comparing sitagliptin to placebo groups, the occurrence of severe hypoglycemia was twice as common in CKD versus non-CKD cohorts; however, treatment groups showed no differences despite slightly lower HbA_1c levels in the sitagliptin group [32]. Safety data from 12 randomized, placebo-controlled phase 2b/phase 3 trials were analyzed, revealing that treatment with dapagliflozin at various doses is linked to an elevated risk of vulvovaginitis or balanitis due to glucosuria induction [36]. A systematic review and meta-analysis illustrated that DPP4is may mitigate the risk of patients developing genitourinary tract infections associated with SGLT2is use [37].

The current study supports previous research findings regarding the effectiveness and safety of FDC D/S in T2DM patients with CKD. Notably, the FDC D/S therapy led to significant reductions in HbA_1c levels (P < 0.001) after 3 months of treatment. There were consistently significant reductions in FPG, PPG levels, and serum creatinine levels. A significant improvement in eGFR values was also observed, underscoring its role in preserving renal function. This study provides compelling evidence validating the effectiveness and safety of the combination therapy of SGLT2is and DPP4is in the management of T2DM and CKD. Common AEs included UTIs, dehydration, hypoglycemia, and genital mycotic infections.

The multicenter, observational design of the study facilitated the assessment of real-world outcomes. Comprehensive data collection encompassing patient demographics, medical history, and CKD progression offered an understanding of the study population. Additionally, the utilization of objective outcome measures such as HbA_1c, FPG, PPG, serum creatinine, and eGFR further strengthened the validity of the outcomes.

This retrospective, questionnaire-based study design posed inherent limitations, introducing bias and affecting the reliability of the findings. Dose adjustments for sitagliptin are recommended in those with moderate-to-severe CKD or ESRD [38]; however, the dosage remained unchanged in our study. In addition, there was no control group, which prevented the effectiveness of the treatment under investigation from being compared. Potential confounding variables, such as comorbidities, concomitant medications, and lifestyle factors, might not have been adequately accounted for, potentially influencing treatment outcomes.

This real-world evidence on using FDC D/S in treating T2DM patients with CKD risk showed that it effectively decreases HbA_1c, FPG, and PPG levels and improves eGFR values. This study contributes to the evidence supporting the effectiveness and safety of the combination of SGLT2is and DPP4is in the management of T2DM and CKD. The findings underscore the importance of individualized treatment approaches tailored to renal function and cardiovascular risk profiles. More research is required to elucidate the long-term effects and optimal dosing strategies of combination therapy in diverse patient populations.

Acknowledgments

The authors extend a special thanks to Mr. Animesh Sahoo, Mr. Sumit Kakirde and Ms. Pallavi Vanmali. The authors also thank BioQuest Solutions for the medical writing support.

Financial Disclosure

This research was funded by USV Private Limited.

Conflict of Interest

The present study was initiated and supported by USV Primate Limited. The authors Rohan Narayan Kesarkar, Ashish Prasad and Abhijit Pednekar are employees of USV, and the rest of the authors have indicated that they have no other conflict of interest regarding the content of this article.

Informed Consent

The data collected were from the patient’s past records and as the data collected were anonymous from the patient’s health records, informed consent was not taken.

Author Contributions

Animesh Maiti, Rohan Narayan Kesarkar, Ashish Prasad, and Abhijit Pednekar have contributed to the study design, data support, data analysis, manuscript development, review, and revisions. Rest of the authors have contributed to the data support and manuscript review.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Abbreviations

ADA: American Diabetes Association; AE: adverse event; AKI: acute kidney injury; ASCVD: atherosclerotic cardiovascular disease; CKD: chronic kidney disease; CRF: case report form; CI: confidence interval; CVD: cardiovascular disease; D/S: dapagliflozin and sitagliptin; DPP4i: dipeptidyl peptidase-4 inhibitor; eGFR: estimated glomerular filtration rate; ESRD: end-stage kidney disease; FPG: fasting plasma glucose; FDC: fixed-dose combination; GLP-1: glucagon-like peptide-1; GFR: glomerular filtration rate; HbA_1c: glycated hemoglobin; HR: hazard ratio; IRB: Institutional Review Board; PPG: post-prandial glucose; OAD: oral antidiabetic drug; RR: risk ratio; SGLT2i: sodium-glucose cotransporter-2 inhibitor; T2DM: type 2 diabetes mellitus; UTI: urinary tract infection

1. Xie D, Ma T, Cui H, Li J, Zhang A, Sheng Z, Xie Y. Global burden and influencing factors of chronic kidney disease due to type 2 diabetes in adults aged 20-59 years, 1990-2019. Sci Rep. 2023;13(1):20234.
   doi pubmed
2. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2016;5(1):49-56.
   pubmed
3. Deng Y, Li N, Wu Y, Wang M, Yang S, Zheng Y, Deng X, et al. Global, regional, and national burden of diabetes-related chronic kidney disease from 1990 to 2019. Front Endocrinol (Lausanne). 2021;12:672350.
   doi pubmed
4. Hasan M, Sutradhar I, Gupta RD, Sarker M. Prevalence of chronic kidney disease in South Asia: a systematic review. BMC Nephrol. 2018;19(1):291.
   doi pubmed
5. Jitraknatee J, Ruengorn C, Nochaiwong S. Prevalence and risk factors of chronic kidney disease among type 2 diabetes patients: a cross-sectional study in primary care practice. Sci Rep. 2020;10(1):6205.
   doi pubmed
6. Hernandez D, Espejo-Gil A, Bernal-Lopez MR, Mancera-Romero J, Baca-Osorio AJ, Tinahones FJ, Armas-Padron AM, et al. Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population. BMC Nephrol. 2013;14:151.
   doi pubmed
7. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412.
   doi pubmed
8. Siddiqui K, George TP, Joy SS, Alfadda AA. Risk factors of chronic kidney disease among type 2 diabetic patients with longer duration of diabetes. Front Endocrinol (Lausanne). 2022;13:1079725.
   doi pubmed
9. Satheesh SS, Mourya GVP, SS, Am I, Parimi PD, Dudhagonda SR. EPH161: a scoping review on estimation of economic burden of chronic kidney diseases in India. Value Health. 2022;25(7):S464.
   doi
10. Sharma S, Kalra D, Rashid I, Mehta S, Maity MK, Wazir K, Gupta S, et al. Assessment of health-related quality of life in chronic kidney disease patients: a hospital-based cross-sectional study. Medicina (Kaunas). 2023;59(10):1788.
    doi pubmed
11. Venkatesan V, Lopez-Alvarenga JC, Arya R, Ramu D, Koshy T, Ravichandran U, Ponnala AR, et al. Burden of type 2 diabetes and associated cardiometabolic traits and their heritability estimates in endogamous ethnic groups of India: findings from the INDIGENIUS consortium. Front Endocrinol (Lausanne). 2022;13:847692.
    doi pubmed
12. Chen SC, Hung CC, Kuo MC, Lee JJ, Chiu YW, Chang JM, Hwang SJ, et al. Association of dyslipidemia with renal outcomes in chronic kidney disease. PLoS One. 2013;8(2):e55643.
    doi pubmed
13. Yi Y, Kwon EJ, Yun G, Park S, Jeong JC, Na KY, Chin HJ, et al. Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study. Sci Rep. 2024;14(1):2081.
    doi pubmed
14. Chadha M, Das AK, Deb P, Gangopadhyay KK, Joshi S, Kesavadev J, Kovil R, et al. Expert opinion: optimum clinical approach to combination-Use of SGLT2i + DPP4i in the Indian diabetes setting. Diabetes Ther. 2022;13(5):1097-1114.
    doi pubmed
15. Navaneethan SD, Zoungas S, Caramori ML, Chan JCN, Heerspink HJL, Hurst C, Liew A, et al. Diabetes management in chronic kidney disease: synopsis of the 2020 KDIGO clinical practice guideline. Ann Intern Med. 2021;174(3):385-394.
    doi pubmed
16. McMurray JJV, Wheeler DC, Stefansson BV, Jongs N, Postmus D, Correa-Rotter R, Chertow GM, et al. Effect of dapagliflozin on clinical outcomes in patients with chronic kidney disease, with and without cardiovascular disease. Circulation. 2021;143(5):438-448.
    doi pubmed
17. Mosenzon O, Wiviott SD, Cahn A, Rozenberg A, Yanuv I, Goodrich EL, Murphy SA, et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019;7(8):606-617.
    doi pubmed
18. Triozzi JL, Parker Gregg L, Virani SS, Navaneethan SD. Management of type 2 diabetes in chronic kidney disease. BMJ Open Diabetes Res Care. 2021;9(1):e002300.
    doi pubmed
19. Gong Y, Bai X, Zhang D, Yang X, Qin Z, Yang Y, Zhou Y, et al. Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis. 2024;23(1):157.
    doi pubmed
20. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care. 2003;26(10):2929-2940.
    doi pubmed
21. Tomonaga O, Sakura H, Hashimoto N, Sasamoto K, Ohashi H, Hasumi S, Ujihara N, et al. Renal function during an open-label prospective observational trial of sitagliptin in patients with diabetes: a sub-analysis of the JAMP study. J Clin Med Res. 2018;10(1):32-40.
    doi pubmed
22. Ioannidis I. Diabetes treatment in patients with renal disease: Is the landscape clear enough? World J Diabetes. 2014;5(5):651-658.
    doi pubmed
23. Bhattacharjee R, Rai M, Joshi P, Prasad A, Birla A. The Real DAPSI: A Real-World Retrospective Study on Assessing the Efficacy and Safety of a Fixed-Dose Combination of Dapagliflozin and Sitagliptin in the Indian Population. Cureus. 2023;15(10):e46767.
    doi pubmed
24. Elnaem MH, Mansour NO, Nahas AF, Baraka MA, Elkalmi R, Cheema E. Renal outcomes associated with the use of non-insulin antidiabetic pharmacotherapy: a review of current evidence and recommendations. Int J Gen Med. 2020;13:1395-1409.
    doi pubmed
25. “Fdc01.01.2022 to 25.08.2022.Pdf.” n.d. Accessed May 30, 2024. https://cdsco.gov.in/opencms/resources/UploadCDSCOWeb/2018/UploadApprovalMarketingFDC/fdc01.01.2022%20to%2025.08.2022.pdf.
26. Chapter 1: Definition and classification of CKD. Kidney International Supplements. 2013;3:19-62.
    doi
27. Provenzano M, Serra R, Michael A, Bolignano D, Coppolino G, Ielapi N, Serraino GF, et al. Smoking habit as a risk amplifier in chronic kidney disease patients. Sci Rep. 2021;11(1):14778.
    doi pubmed
28. Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002983.
    doi pubmed
29. Liu J, Li L, Li S, Jia P, Deng K, Chen W, Sun X. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):2824.
    doi pubmed
30. Kidney Disease: Improving Global Outcomes CKDWG. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314.
    doi pubmed
31. Kanozawa K, Noguchi Y, Sugahara S, Nakamura S, Yamamoto H, Kaneko K, Kono R, et al. The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a small dose in type 2 diabetic patients with a renal dysfunction when changed from other DPP-4 inhibitors: REAL trial. Clin Exp Nephrol. 2018;22(4):825-834.
    doi pubmed
32. Engel SS, Suryawanshi S, Stevens SR, Josse RG, Cornel JH, Jakuboniene N, Riefflin A, et al. Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS. Diabetes Obes Metab. 2017;19(11):1587-1593.
    doi pubmed
33. Li D, Shi W, Wang T, Tang H. SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(8):1972-1976.
    doi pubmed
34. Ray S, Ezhilan J, Karnik R, Prasad A, Dhar R. Expert opinion on fixed dose combination of dapagliflozin plus sitagliptin for unmet cardiovascular benefits in type 2 diabetes mellitus. J Diabetol. 2024;15(2):131-141.
    doi
35. Scheen AJ. Efficacy / safety balance of DPP-4 inhibitors versus SGLT2 inhibitors in elderly patients with type 2 diabetes. Diabetes Metab. 2021;47(6):101275.
    doi pubmed
36. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013;27(5):479-484.
    doi pubmed
37. Fadini GP, Bonora BM, Mayur S, Rigato M, Avogaro A. Dipeptidyl peptidase-4 inhibitors moderate the risk of genitourinary tract infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab. 2018;20(3):740-744.
    doi pubmed
38. Bergman AJ, Cote J, Yi B, Marbury T, Swan SK, Smith W, Gottesdiener K, et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care. 2007;30(7):1862-1864.
    doi pubmed

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