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Effectiveness and Safety Outcomes of SGLT2 Inhibitors in Type 2 Diabetes and Use of Drugs with Nephrotoxic Potential

Yang, Lanting (2024) Effectiveness and Safety Outcomes of SGLT2 Inhibitors in Type 2 Diabetes and Use of Drugs with Nephrotoxic Potential. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Sodium Glucose Cotransporter 2 inhibitors (SGLT2is) improve the cardiovascular and renal outcomes in patients with Type 2 diabetes (T2D). However, there has been limited evidence on the usage pattern of drugs with nephrotoxic potential (NxP) and the potential offsetting of SGLT2i's renal benefits by such drugs. This dissertation aims to bridge these gaps by examining the trajectories of the use of drugs with NxP and the comparative cardiovascular, safety, and renal outcomes of SGLT2i versus DPP4 inhibitors (DPP4is) in Medicare beneficiaries with T2D.
Chapter 3 examined the use patterns of drugs with NxP among T2D patients following the initiation of SGLT2i therapy. It identified distinct trajectories of use of drugs with NxP, with 53.9%, 21.8% and 24.3% of patients demonstrating low, high and no use of these drugs. The study also found patient demographics and clinical factors were associated with the drug usage patterns.
In Chapter 4, we compared the cardiovascular and safety outcomes of SGLT2i versus DPP4i in T2D patients. The findings demonstrated that SGLT2is are associated with a decreased risk of hospitalized heart failure, major adverse cardiovascular events, alongside a favorable safety profile compared to DPP4is.
Finally, in Chapter 5, we examined the effects of concurrent use of drug with NxP and SGLT2is on renal outcomes in T2D patients without a history of chronic kidney disease (CKD). We found that SGLT2is were associated with a lower risk of CKD and end-stage renal disease, and these benefits persisted regardless of the use of NxP drugs. Furthermore, a higher number of drugs with NxP used was associated with an increased risk of CKD, underscoring the importance of cautious NxP drug use in T2D patients.
The findings presented in this dissertation fill crucial gaps in the literature, suggesting that SGLT2i therapy not only provides substantial cardiovascular benefits and a favorable safety profile, but also mitigates renal risk, even in the presence of use of drugs with NxP. These insights highlight the importance of SGLT2is in the management of T2D, guiding the development of treatment strategies that effectively reduce renal risk while enhancing overall treatment efficacy.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Yang, LantingLAY26@PITT.EDULAY260000-0003-0597-9062
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKirisci,
Committee ChairHernandez, Inmaculadainhernandez@health.ucsd.edu0000-0002-0118-4986
Committee MemberKane-Gill, SandraKane-Gill@pitt.edu0000-0001-7523-4846
Committee MemberEmpey, Kerrykme33@pitt.edu0000-0001-7531-2541
Committee MemberSuh, KanghoKAS551@pitt.edu0000-0002-7906-9398
Date: 25 April 2024
Date Type: Publication
Defense Date: 15 December 2023
Approval Date: 25 April 2024
Submission Date: 4 April 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 140
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: SGLT2 inhibitors, drugs with nephrotoxic potential, type 2 diabetes, chronic kidney diseases, heart failure
Date Deposited: 25 Apr 2024 15:39
Last Modified: 25 Apr 2024 15:39


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