Large-scale multinational trends in the use of cardioprotective antihyperglycemic agents as first-line therapy in patients with type 2 diabetes and cardiovascular disease: a LEGEND-T2DM study
Abstract Body (Do not enter title and authors here): Background: US guidelines for type 2 diabetes (T2DM) recommend metformin as first-line anti-hyperglycemic therapy (AHT), but prioritizing the use of AHTs that reduce cardiovascular disease (CVD) risk – GLP1-RAs and SGLT2is – is increasingly suggested for people with CVD. We examine the multinational use patterns of GLP1-RAs, SGLT2is, DPP4is, and sulfonylureas (SUs) as first-line therapies for patients with CVD.
Methods: In 10 US and 6 non-US databases between 2016 and 2021 mapped to a common data model [A], we measured yearly initiation of GLP1-RAs, SGLT2is, DPP4is, and SUs as first-line AHTs in patients with T2DM with and without CVD [B]. We also compared the initiation of the drug classes as second-line after metformin. We calculated the annual rate of change in proportional initiation of each drug class as first-line AHT and assessed differences in trends as group x time interactions in linear mixed models.
Results: Across all data sources, 3.3 million patients with T2DM used GLP1-RAs, SGLT2is, DPP4is, or SUs as first-line AHTs, and 3.9m initiated these drug classes as second-line AHT after metformin. Within the first-line cohort, 1.4m (41%) had established CVD compared with 1.2m (31%) in the second-line cohort. For GLP1-RAs and SGLT2is, the annual rate of their relative use as first-line agents increased among patients with T2DM with CVD (GLP1RAs: ranging 1.3-5.4% in US [C] and 0.3-0.8% in non-US [D], SGLT2is: 2.1-12.9% in US [E] and 8.1-10.6% in non-US databases [F]). There was a larger relative increase in the use of SGLT2i and a smaller increase in GLP1RA use in CVD vs non-CVD cohorts (Pinteraction <.001). While there was a larger increase in GLP1RAs uptake in the US cohorts, SGLT2i use increased more in non-US cohorts ([C-F], Pinteraction <.001 for all, except .01 for SGLT2i). Of note, across cohorts, the uptake of GLP1RA and SGLT2i as first-line was higher than second-line use among those with CVD (Pinteraction <.001). In contrast, DPP4i and SU use as first-line was lower than GLP1RA and SGLT2is and decreased over time (P<.001).
Conclusions: In a large-scale multinational, federated cohort of patients with T2DM, the use of cardioprotective agents increased as first-line AHT, with variation in SGLT2i and GLP1RAs uptake across study cohorts.
Thangaraj, Phyllis
( Yale University
, New Haven
, Connecticut
, United States
)
Dorr, David
( OHSU
, Portland
, Oregon
, United States
)
Duarte-salles, Talita
( IDIAPJGol
, Barcelona
, Spain
)
Lau, Wallis
( UCL
, London
, United Kingdom
)
Liu, Yuntian
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Lu, Yuan
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Man, Kenneth
( UCL
, London
, United Kingdom
)
Minty, Evan
( University of Calgary
, Calgary
, Alberta
, Canada
)
Richter, Lauren
( Columbia University Irving Medical Center
, New York
, New York
, United States
)
Ross, Joseph
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Shah, Nigam
( Stanford University
, Palo Alto
, California
, United States
)
Aminorroaya, Arya
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Ryan, Patrick
( Janssen Research and Development
, Chesapeake
, Virginia
, United States
)
Schuemie, Martijn
( Janssen Research and Development
, Chesapeake
, Virginia
, United States
)
Hripcsak, George
( Columbia University Irving Medical Center
, New York
, New York
, United States
)
Krumholz, Harlan
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Suchard, Marc
( UCLA
, Los Angeles
, California
, United States
)
Khera, Rohan
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Dhingra, Lovedeep
( Yale School Of Medicine
, New Haven
, Connecticut
, United States
)
Pedroso, Aline
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Zhou, Jin
( UCLA
, Los Angeles
, California
, United States
)
Blacketer, Clair
( Janssen Research and Development
, Chesapeake
, Virginia
, United States
)
Bu, Fan
( UCLA
, Los Angeles
, California
, United States
)
Chai, Yi
( University of Hong Kong
, Pokfulam
, Hong Kong
)
Chattopadhyay, Shounak
( UCLA
, Los Angeles
, California
, United States
)
Author Disclosures:
Phyllis Thangaraj:DO NOT have relevant financial relationships
| David Dorr:DO NOT have relevant financial relationships
| Talita Duarte-Salles:No Answer
| Wallis Lau:DO NOT have relevant financial relationships
| Yuntian Liu:DO NOT have relevant financial relationships
| Yuan Lu:No Answer
| Kenneth Man:No Answer
| Evan Minty:DO have relevant financial relationships
;
Consultant:Janssen Research and Development:Past (completed)
; Consultant:Orpyx Medical Technologies:Active (exists now)
| Lauren Richter:No Answer
| Joseph Ross:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Johnson and Johnson:Active (exists now)
| Nigam Shah:DO NOT have relevant financial relationships
| Arya Aminorroaya:DO NOT have relevant financial relationships
| Patrick Ryan:No Answer
| Martijn Schuemie:No Answer
| George Hripcsak:No Answer
| Harlan Krumholz:DO have relevant financial relationships
;
Individual Stocks/Stock Options:Element Science:Active (exists now)
; Research Funding (PI or named investigator):Pfizer:Active (exists now)
; Research Funding (PI or named investigator):Kenvue:Active (exists now)
; Research Funding (PI or named investigator):Janssen:Active (exists now)
; Ownership Interest:Ensight-AI:Active (exists now)
; Ownership Interest:Refactor Health:Active (exists now)
; Ownership Interest:Hugo Health:Active (exists now)
; Advisor:F-Prime:Active (exists now)
; Individual Stocks/Stock Options:Identifeye:Active (exists now)
| Marc Suchard:DO have relevant financial relationships
;
Research Funding (PI or named investigator):National Institutes of Health:Active (exists now)
; Consultant:Johnson & Johnson:Active (exists now)
; Research Funding (PI or named investigator):Department of Veterans Affairs:Active (exists now)
; Research Funding (PI or named investigator):Food & Drug Administration:Active (exists now)
| Rohan Khera:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Bristol-Myers Squibb:Active (exists now)
; Ownership Interest:Ensight-AI, Inc:Active (exists now)
; Ownership Interest:Evidence2Health LLC:Active (exists now)
; Research Funding (PI or named investigator):BridgeBio:Active (exists now)
; Research Funding (PI or named investigator):Novo Nordisk:Active (exists now)
| Lovedeep Dhingra:DO NOT have relevant financial relationships
| Aline Pedroso:DO NOT have relevant financial relationships
| Jin Zhou:No Answer
| Clair Blacketer:DO have relevant financial relationships
;
Employee:Janssen Research & Development:Active (exists now)
| Fan Bu:No Answer
| Yi Chai:DO NOT have relevant financial relationships
| Shounak Chattopadhyay:DO NOT have relevant financial relationships
