Use of Second-line Diabetes Mellitus Medications and Adverse Events Among Older Adults After the Introduction of Glucagon-like Peptide-1 Receptor Agonists in Ontario, Canada: A Retrospective Cohort Study

Dec 19, 2025Canadian journal of diabetes

Use of second-choice diabetes medicines by older adults after new diabetes drugs became available in Ontario, Canada

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Abstract

In 2022, the use of SGLT2 inhibitors surpassed DPP-4 inhibitors, marking a significant shift in diabetes medication trends among older adults.

Metformin was the most dispensed diabetes medication until 2019, when second-line medications became more prevalent.
DPP-4 inhibitors had the highest usage among second-line drugs until 2022, when SGLT2 inhibitors overtook them.
Insulin users experienced the highest rate of hypoglycemia at an average of 0.13% per month.
Gastrointestinal events were more common among users of GLP-1 receptor agonists, with an average incidence of 0.23% for diverticular disease.
The introduction of GLP-1 receptor agonists did not correlate with any significant changes in medication trends according to joinpoint models.

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OBJECTIVE: Describe incident-use of second-line diabetes medications and serious adverse events among older adults before and after the introduction of GLP-1 receptor agonists (RAs) METHODS: We conducted a population-based cohort study from June 2011 to March 2023 using administrative data from Ontario, Canada. We identified individuals aged 66+ with a new prescription for a second-line diabetes medication and recent history of metformin use. We calculated the number and proportion of individuals using medications monthly with hypoglycemia and gastrointestinal events, stratified by drug class. Joinpoint models were used to determine if any significant changes aligned with the introduction of GLP-1 RAs.

RESULTS: Metformin was initially the most dispensed diabetes drug (peak 105,245 individuals treated in 2016), but its use was overtaken by second-line medications in 2019. Among second-line drugs, DPP-4 inhibitors were dominant (peak 77,477 individuals in 2020). Use of SGLT2 inhibitors surpassed DPP-4 inhibitor use in 2022. Adverse events of interest were rare, however insulin had the highest percentage of individuals affected with hypoglycemia (average 0.13% per month), while more individuals using second-line medications were affected with gastrointestinal outcomes (average 0.23% for diverticular disease in those using GLP-1 RA). Joinpoint models did not reveal any breaks in trend during the time of GLP-1 introduction.

CONCLUSIONS: Metformin was the most common drug class used, however the use of second-line medications such as SGLT2-i, DPP-4-i, and GLP-1 RAs exceeded the number of individuals using metformin in recent years - a major shift from historical trends.

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Use of Second-line Diabetes Mellitus Medications and Adverse Events Among Older Adults After the Introduction of Glucagon-like Peptide-1 Receptor Agonists in Ontario, Canada: A Retrospective Cohort Study

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