Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease
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Yu Deng1, Farhad Ghamsari2, Alice Lu1
1Center for Health Information Partnerships, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Abstract:
Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately-one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparative effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with diagnosed incident CKD, CKD hospitalization, and eGFR < 45 mL/min in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors was significantly associated with lower risk of diagnosed CKD incidence in both primary analysis (hazard ratio, 0.43; 95 % CI, [0.22;0.87]; p-value,0.02) and secondary analysis (hazard ratio, 0.42; 95 % CI, [0.19;0.92]; p-value, 0.03) compared to use of Sulfonylureas (SU) as a second-line ADM. However, significant associations were not observed when using eGFR < 45 mL/min as the endpoint. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower risk of diagnosed incident CKD (hazard ratio, 0.7; 95 % CI, [0.53;0.96]; p-value, 0.03) and lower risk of CKD hospitalization (hazard ratio, 0.6; 95 % CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of glucagon-like peptide 1 receptor agonists (GLP-1RA), Thiazolidinediones (TZD), insulin and diagnosed CKD incidence, hospitalization or eGFR < 45 mL/min compared to use of SU as a second-line ADM.
Insights
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors show potential in reducing chronic kidney disease (CKD) incidence in type 2 diabetes mellitus (T2DM) patients. Further research is needed to confirm these findings in real-world settings.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Chronic kidney disease (CKD) is a prevalent complication of type 2 diabetes mellitus (T2DM), affecting approximately one-third of patients.
- While several anti-diabetic medications (ADMs) demonstrate efficacy in clinical trials for preventing CKD progression, their comparative effectiveness as second-line treatments in real-world practice remains unclear.
Purpose of the Study:
- To investigate the association of second-line ADMs with diagnosed incident CKD, CKD hospitalization, and estimated glomerular filtration rate (eGFR) < 45 mL/min in T2DM patients.
- To compare the effectiveness of SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 receptor agonists (GLP-1RA), thiazolidinediones (TZD), and insulin against sulfonylureas (SU) as second-line ADMs for CKD outcomes.
Main Methods:
- Utilized real-world data from electronic health records of T2DM patients.
- Employed survival analysis to assess the association between different second-line ADMs and CKD-related outcomes, including diagnosed CKD incidence, CKD hospitalization, and eGFR < 45 mL/min.
- Conducted primary and sensitivity analyses to evaluate the robustness of the findings.
Main Results:
- Sodium-glucose cotransporter 2 (SGLT-2) inhibitors were significantly associated with a lower risk of diagnosed CKD incidence compared to sulfonylureas (SU) (HR, 0.43; 95% CI, [0.22;0.87]; p=0.02).
- Dipeptidyl peptidase 4 (DPP-4) inhibitors showed a significant association with lower risk of diagnosed incident CKD (HR, 0.7; 95% CI, [0.53;0.96]; p=0.03) and CKD hospitalization (HR, 0.6; 95% CI, [0.37;0.96]; p=0.04) in primary analysis, but not in sensitivity analysis.
- No significant associations were found for GLP-1RA, TZD, or insulin compared to SU for any CKD outcome.
Conclusions:
- SGLT-2 inhibitors demonstrate a significant protective effect against diagnosed CKD incidence in T2DM patients when used as second-line therapy compared to SUs.
- DPP-4 inhibitors may offer benefits for CKD incidence and hospitalization, though further validation is needed.
- Real-world data suggests differential effects of second-line ADMs on CKD outcomes in T2DM patients, highlighting the importance of medication choice.
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