Fast Five Quiz: Hyperglycemia Associated With Type 2 Diabetes

Anne L. Peters, MD; Romesh Khardori, MD, PhD


June 28, 2023

In patients with type 2 diabetes who are intensified to insulin therapy, combination therapy with a glucagon-like peptide 1 (GLP-1) receptor agonist has been shown to have greater efficacy and durability of glycemic treatment effect than treatment intensification with insulin alone. In the DUAL VIII randomized controlled trial, patients who received combination GLP-1 receptor agonist–insulin therapy demonstrated longer durability of the treatment effect compared with those receiving basal insulin alone (median, > 2 years vs about 1 year). There were no new or unexpected safety and tolerability issues and no treatment-related deaths.

Other data support initial combination therapy for more quickly attaining glycemic goals as well as later combination therapy for longer durability of glycemic effect. In the 5-year VERIFY trial, participants receiving the initial combination of metformin and the dipeptidyl peptidase 4 inhibitor vildagliptin had a slower decline of glycemic control vs those who received metformin alone and those who received vildagliptin added sequentially to metformin. The median observed time to treatment failure in the metformin group was 36.1 months, whereas the median time to treatment failure for patients receiving early combination therapy could only be estimated to be beyond the study duration at 61.9 months. These results suggest that more intensive early treatment may be beneficial and may reasonably be considered through a shared decision-making process with patients, as appropriate. In patients presenting with A1c levels 1.5%-2% above target, the American Diabetes Association recommends consideration of initial combination therapy.

Learn more about the management of hyperglycemia in type 2 diabetes.


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