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dc.contributor.advisorScheneeweiss, Sebastian
dc.contributor.authorShin, HoJin
dc.date.accessioned2021-07-13T04:57:39Z
dash.embargo.terms2023-07-12
dc.date.created2021
dc.date.issued2021-05-13
dc.date.submitted2021-05
dc.identifier.citationShin, HoJin. 2021. Evaluating novel glucose-lowering therapies in first-line treatment for type 2 diabetes. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
dc.identifier.other28496885
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368274*
dc.description.abstractType 2 diabetes (T2D) patients have increased risk of cardiovascular disease (CVD) due to chronic hyperglycemia and prevalent cardiovascular risk factors, such as obesity. CVD affects approximately one-third of the T2D population and accounts for 50%-80% of mortality. The growing burden of cardiovascular disease (CVD) has shifted the paradigm of T2D treatment to include the management of cardiovascular risk in addition to glycemic control. Since 2008, in response to the potential for increased cardiovascular risk with certain existing glucose-lowering drugs, the U.S. Food and Drug Administration (FDA) has mandated cardiovascular outcome trials (CVOTs) to evaluate the safety of new glucose-lowering drugs. The cardiovascular benefits from CVOTs of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have been the catalyst for a preferred second-line treatment for patients with T2D and CVD by treatment guidelines—further raising the question whether SGLT-2i could be used as first-line treatment for T2D patients with CVD in place of metformin, recommended first-line. With no head-to-head randomized controlled trials, well-conducted large non-randomized studies based on real-world data could provide information on the effectiveness for cardiovascular outcomes and safety of first-line SGLT-2i compared with metformin. Therefore, we investigated risk of cardiovascular and safety outcomes among adults with T2D initiating first-line SGLT-2i versus metformin using claims data, along with methodological challenges and potential sources of bias arising in this setting. In Chapter 1, we evaluated utilization trends and predictors of first-line antidiabetic treatment in adult patients with T2D. From 2013 through 2019, metformin was by far the most frequent first-line treatment. Although the use of SGLT-2i and glucagon-like peptide 1 receptor agonists (GLP-1RA) was low, uptake of these drugs increased among patients with CVD. Initiators of antidiabetic drugs with cardiovascular benefits (SGLT-2i and GLP-1RA) were more likely to be younger, and had prevalent CVD or higher socioeconomic status compared with metformin. In Chapter 2, we assessed evolving imbalances in characteristics of patients initiating first-line SGLT-2i versus metformin for T2D treatment. From 2013 through 2019, compared with metformin, characteristics of patients initiating first-line SGLT-2i changed rapidly channeling to those with high cardiovascular risk, perhaps challenging confounding control in observational studies of first-line SGLT-2i. Finally, in Chapter 3, we examined cardiovascular and safety outcomes comparing first-line SGLT-2i versus metformin among adults with T2D. Compared with metformin, SGLT-2i showed a similar risk of a composite of hospitalization for myocardial infarction or stroke, and all-cause mortality, but a lower risk of a composite of hospitalization for heart failure and all-cause mortality, driven by a lower risk of hospitalization for heart failure. SGLT-2i had a comparable safety profile to metformin except for an increased risk of genital infections.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectCardiovascular outcomes
dc.subjectGlucose-lowering drugs
dc.subjectMetformin
dc.subjectSGLT-2i
dc.subjectType 2 diabetes
dc.subjectEpidemiology
dc.titleEvaluating novel glucose-lowering therapies in first-line treatment for type 2 diabetes
dc.typeThesis or Dissertation
dash.depositing.authorShin, HoJin
dash.embargo.until2023-07-12
dc.date.available2021-07-13T04:57:39Z
thesis.degree.date2021
thesis.degree.grantorHarvard University Graduate School of Arts and Sciences
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
dc.contributor.committeeMemberPatorno, Elisabetta
dc.contributor.committeeMemberGlynn, Robert J.
dc.type.materialtext
thesis.degree.departmentPopulation Health Sciences
dc.identifier.orcid0000-0002-2032-6134
dash.author.emailhos739@mail.harvard.edu


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