Skill Checkup: A 55-Year-Old Man With Type 2 Diabetes and High A1C Level Despite Previous Treatments

Romesh Khardori, MD, PhD


April 27, 2023

Of the treatment this patient currently is using, metformin has the highest efficacy in terms of reducing hyperglycemia. DPP-4 inhibitors and SGLT2 inhibitors are considered moderately effective in reducing hyperglycemia, associated with HbA1C reductions of about 0.5%-1.0% as monotherapy and additional reductions of 0.8% and 1.2%, respectively, when added to metformin. Additionally, SGLT2 inhibitors have cardiovascular, renal, and weight reduction benefits compared with DPP-4 inhibitors.

GLP-1 RAs are highly potent treatments and would provide more robust reduction in HbA1C, along with cardiovascular and weight reduction benefits. Long-acting GLP-1 RAs (liraglutide and the once-weekly options) are associated with additional HbA1C reductions of about 1.5%-2%. Given the overlapping mechanisms of action of combined incretin therapy with a DPP-4 inhibitor and GLP-1 RA, the DPP-4 agent would be discontinued as the GLP-1 RA was initiated.

A once-daily oral GLP-1 RA (semaglutide) is more effective than the DPP-4 inhibitors or SGLT2 inhibitors in clinical trials and has demonstrated cardiovascular safety. However, this would not reduce the patient's bothersome daily pill count. With adequate discussion and education, he likely would benefit from an injected GLP-1 RA, with once-daily or once-weekly options available.

Basal insulin remains as a potent treatment for reducing hyperglycemia. However, it is associated with concerns about weight gain and hypoglycemia. For patients with T2D, the ADA recommends a GLP-1 RA before considering basal insulin.


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