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The DPP/DPPOS research showed that gastrointestinal symptoms were more common in metformin than placebo participants but declined over time

In cases where SGLT2i or GLP-1RAs are used due to coexisting atherosclerotic cardiovascular disease, heart failure, chronic kidney disease or stroke, and the target HbA1c is unmet, integration of another class of drug with demonstrated clinical benefits for the specified comorbidity is advised

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The American Diabetes Association (ADA) guidelines recognize GLP-1 receptor agonists as preferred agents for patients with type 2 diabetes who require additional glucose-lowering therapy beyond metformin, particularly those with established cardiovascular disease or chronic kidney disease, with preference given to agents with proven cardiovascular benefit