The Clinical Impact of Discontinuation of Sodium-Glucose Transport Protein 2 Inhibitors (SGLT2is): A Targeted Literature Review
Author(s)
Alison M. Bjornson, MSc1, Lindsay G. Bengtson, PhD2, Shiraz El Adam, MSc1, Shelagh M. Szabo, MSc1, Bonnie M. Donato, PhD2;
1Broadstreet HEOR, Vancouver, BC, Canada, 2Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA
1Broadstreet HEOR, Vancouver, BC, Canada, 2Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA
OBJECTIVES: Treatment with SGLT2is reduces the risk of cardiorenal events. Changes to reimbursement and formulary positioning could lead to lack of treatment initiation, or temporary or permanent discontinuation, of SGLT2is. As the clinical impacts of SGLT2i discontinuation are unclear, a targeted review was performed to summarize the risk of clinical events following SGLT2i discontinuation.
METHODS: Keyword searching (for outcomes, interventions) in PubMed and Google Scholar was performed to identify manuscripts published before SEP-2024. Articles were screened against review PICOS criteria. The risk (hazard ratios [HR], incidence rate ratios [IRR], 95% confidence intervals [CI]) and time to events following discontinuation were summarized.
RESULTS: Nine studies were included: a post-hoc EMPEROR trial-based analysis, two case reports, three single-center studies, and three database analyses. In the post-hoc analysis, by 30-days post-withdrawal, the HR (95%CI) for hospitalization for heart failure (HF) or cardiovascular (CV) mortality was 1.18 (95%CI 0.78-1.80) for patients discontinuing empagliflozin (SGLT2i) vs. placebo. EMPEROR was underpowered to detect significant differences in events post-discontinuation. In one case report, HF symptoms in a patient with type 2 diabetes (T2D) one month following empagliflozin discontinuation was described; in the other, a patient experienced HF-related mortality 20 days following empagliflozin discontinuation. The six additional studies highlighted the risk of cardiorenal events, readmissions, and mortality following SGLT2i discontinuation. For example, compared to SGLT2i discontinuation, continued use was associated with reduced risk of CV (HR 0.80, 95%CI 0.72-0.88) and renal (HR 0.72, 95%CI 0.63-0.82) events in one database analysis; and in another, was associated with a 48% reduction in all-cause mortality among patients with chronic kidney disease (HR 0.52, 95%CI 0.47-0.56) and T2D (IRR 0.55 [95%CI 0.42-0.73]).
CONCLUSIONS: Evidence is emerging characterizing the clinical risks following SGLT2i discontinuation. Interruptions in patient access, including due to formulary decisions, must be weighed against the potential for severe complications.
METHODS: Keyword searching (for outcomes, interventions) in PubMed and Google Scholar was performed to identify manuscripts published before SEP-2024. Articles were screened against review PICOS criteria. The risk (hazard ratios [HR], incidence rate ratios [IRR], 95% confidence intervals [CI]) and time to events following discontinuation were summarized.
RESULTS: Nine studies were included: a post-hoc EMPEROR trial-based analysis, two case reports, three single-center studies, and three database analyses. In the post-hoc analysis, by 30-days post-withdrawal, the HR (95%CI) for hospitalization for heart failure (HF) or cardiovascular (CV) mortality was 1.18 (95%CI 0.78-1.80) for patients discontinuing empagliflozin (SGLT2i) vs. placebo. EMPEROR was underpowered to detect significant differences in events post-discontinuation. In one case report, HF symptoms in a patient with type 2 diabetes (T2D) one month following empagliflozin discontinuation was described; in the other, a patient experienced HF-related mortality 20 days following empagliflozin discontinuation. The six additional studies highlighted the risk of cardiorenal events, readmissions, and mortality following SGLT2i discontinuation. For example, compared to SGLT2i discontinuation, continued use was associated with reduced risk of CV (HR 0.80, 95%CI 0.72-0.88) and renal (HR 0.72, 95%CI 0.63-0.82) events in one database analysis; and in another, was associated with a 48% reduction in all-cause mortality among patients with chronic kidney disease (HR 0.52, 95%CI 0.47-0.56) and T2D (IRR 0.55 [95%CI 0.42-0.73]).
CONCLUSIONS: Evidence is emerging characterizing the clinical risks following SGLT2i discontinuation. Interruptions in patient access, including due to formulary decisions, must be weighed against the potential for severe complications.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO109
Topic
Clinical Outcomes
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory), SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Urinary/Kidney Disorders