EFFECT MODIFICATION BY MULTIMORBIDITY BURDEN ON THE EFFECTIVENESS AND SAFETY OF SGLT2 INHIBITORS IN OLDER ADULTS WITH T2D: A TARGET TRIAL EMULATION STUDY
Author(s)
Hongjie (Harry) Qian, MS, BScPharm, Kimberly O’Malley, MS, Chintan Dave, PharmD, PhD;
Rutgers University, Rutgers Center for Health Outcomes, Policy, and Economics (HOPE), New Brunswick, NJ, USA
Rutgers University, Rutgers Center for Health Outcomes, Policy, and Economics (HOPE), New Brunswick, NJ, USA
OBJECTIVES: Given the paucity of trial evidence among individuals with high multimorbidity and the biologic plausibility that cumulative chronic disease burden influences treatment response, this study assessed whether the degree of chronic multimorbidity modifies the effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among older adults with type 2 diabetes (T2D).
METHODS: We emulated a target trial using Medicare fee-for-service claims (2013-2021). The new-user, active comparator study was comprised of older beneficiaries aged >65 years with T2D initiating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i). Multimorbidity burden was quantified using the Multimorbidity Weighted Index (MWI), encompassing >80 chronic conditions weighted by their impact on physical quality of life. Patients were classified into MWI terciles, and 1:1 propensity score-matched within each tercile. Primary effectiveness and safety endpoints were heart failure (HHF) and diabetic ketoacidosis (DKA) hospitalizations. Adjusted risk differences (RDs ) per 1,000 person-years were estimated to emphasize patient-relevant absolute risk.
RESULTS: Study cohort included 117,519 matched pairs (mean [SD] age, 73.5 [6.0] years; 52.3% female). Overall, SGLT2i were associated with lower risk of HHF (RD −17.3, 95% CI −19.5, −15.1), but higher DKA risk (RD 1.0, 95% CI 0.5, 1.5). Across MWI tertiles (mild, medium, severe), DKA RDs attenuated from 0.9 (95% CI 0.3, 1.6) to 0.8 (−0.1, 1.7) and 0.7 (−0.5, 2.0) per 1,000 person-years, while HHF benefits increased progressively (RDs −7.5 [95% CI −9.2, −5.8], −16.3 [−19.7, −13.0], and −45.4 [−53.5, −37.3]. Results were consistent across a range of sensitivity and subgroup analyses.
CONCLUSIONS: Among older T2D Medicare beneficiaries, SGLT2i initiation was associated with lower HHF hospitalization and higher DKA risk overall; however, patients with greater multimorbidity experienced larger HHF benefits with attenuated DKA risk. These findings support SGLT2i use in an understudied, multimorbid population largely excluded from clinical trials.
METHODS: We emulated a target trial using Medicare fee-for-service claims (2013-2021). The new-user, active comparator study was comprised of older beneficiaries aged >65 years with T2D initiating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i). Multimorbidity burden was quantified using the Multimorbidity Weighted Index (MWI), encompassing >80 chronic conditions weighted by their impact on physical quality of life. Patients were classified into MWI terciles, and 1:1 propensity score-matched within each tercile. Primary effectiveness and safety endpoints were heart failure (HHF) and diabetic ketoacidosis (DKA) hospitalizations. Adjusted risk differences (RDs ) per 1,000 person-years were estimated to emphasize patient-relevant absolute risk.
RESULTS: Study cohort included 117,519 matched pairs (mean [SD] age, 73.5 [6.0] years; 52.3% female). Overall, SGLT2i were associated with lower risk of HHF (RD −17.3, 95% CI −19.5, −15.1), but higher DKA risk (RD 1.0, 95% CI 0.5, 1.5). Across MWI tertiles (mild, medium, severe), DKA RDs attenuated from 0.9 (95% CI 0.3, 1.6) to 0.8 (−0.1, 1.7) and 0.7 (−0.5, 2.0) per 1,000 person-years, while HHF benefits increased progressively (RDs −7.5 [95% CI −9.2, −5.8], −16.3 [−19.7, −13.0], and −45.4 [−53.5, −37.3]. Results were consistent across a range of sensitivity and subgroup analyses.
CONCLUSIONS: Among older T2D Medicare beneficiaries, SGLT2i initiation was associated with lower HHF hospitalization and higher DKA risk overall; however, patients with greater multimorbidity experienced larger HHF benefits with attenuated DKA risk. These findings support SGLT2i use in an understudied, multimorbid population largely excluded from clinical trials.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO167
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory), SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Geriatrics