Evaluating risks and benefits of Newer Diabetes medications when Used in Routine care (ENDURe)

Abstract

Introduction: Sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 analogues (GLP1a) improve clinical outcomes (e.g., myocardial infarction, stroke, death from CV causes) for adults with type 2 diabetes mellitus. The majority of available data from clinical trials and observational studies are from outpatients. Data on their effectiveness among hospitalized patients, however, are lacking. Methods: We conducted a multicentre, retrospective, cohort study of adults aged 65 years and older with type 2 diabetes mellitus hospitalized between 2017 and 2023 in Ontario. We compared adults newly prescribed an SGLT2i or GLP1a in hospital to adults newly prescribed a DPP4i in hospital. In a sensitivity analysis, new use of sulfonylurea was the comparator. Our primary outcome was the 1-year risk of a composite of all-cause mortality, hospitalization with myocardial infarction, stroke, heart failure, or renal failure. Secondary outcomes included components of the composite, short-term (i.e., 30 day) risk of hypoglycemia, and the 1-year risk of DKA. Results: We identified 6,713 older adults with diabetes who were newly prescribed one of the following medications during an inpatient hospitalization: SGLT2i (N=1520), GLP1 (N=90), DPP4i (N=3726), sulfonylurea (N=1377). Because new use of GLP1 was rare in hospital, we updated our exposure group to SGLT2i alone. Adults who received an SGLT2i were typically younger, and more likely to have heart failure or coronary artery disease compared to adults who received a DPP4i or sulfonylurea. Among adults who received an SGLT2i, at 1-year the primary outcome occurred in 26% compared to 31% who newly received a DPP4i (adjusted hazard ratio [HR] 0.82 95% Confidence Interval [CI] 0.69,0.97). In our sensitivity analysis using sulfonylurea as the comparator group, the hazard ratio for the primary outcome was 0.97 (95% CI 0.80, 1.18). We did not identify an increased risk of DKA or hypoglycemia for SGLT2i compared to DPP4i, though patients receiving an SGLT2i did have a lower rate of 30-day readmission (HR 0.73, 95%CI 0.58-0.92). Conclusion: Among older adults with type 2 diabetes mellitus, newly prescribing an SGLT2i or GLP1 during a hospitalization was uncommon. New use of an SGLT2i was associated with improved outcomes compared to DPP4i but this finding was not robust when new use of a sulfonylurea was the comparator. Future larger studies are needed to provide more definitive results.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by PSI.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Research Ethics Board approval was obtained from St Michaels Hospital on behalf of all participating hospitals with a waiver of patient consent for this retrospective study using routinely collected health data

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon submission of a project proposal to ICES in Ontario, Canada.

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