Choosing Dipeptidyl Peptidase-4 Inhibitors, Sodium-glucose Cotransporter-2 Inhibitors, or Both, as Add-ons to Metformin: Patient Baseline Characteristics Are Crucial.

PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA1C ) targets. A major proportion of those who have not met HbA1C goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these individuals meet their HbA1C goals. This commentary reviews and provides guidance on how baseline factors can assist in the decision between the 2 classes or using both as add-ons to metformin.

METHODS: The important clinical studies comparing the glycemic efficacy of DPP-4i versus SGLT2i or their combination as add-ons to metformin with a focus on the influence of baseline HbA1C on glycemic efficacy will be discussed and interpreted. The impact of estimated glomerular filtration rate and age on the glycemic efficacy of DPP-4i and SGLT2i will also be put into perspective.

FINDINGS: At HbA1C <8.0% to 8.5%, HbA1C lowering is slightly greater with DPP-4i than with SGLT2i as an add-on to metformin; SGLT2i are associated with larger HbA1C improvements than DPP-4i at higher HbA1C levels. In cases of HbA1C ≥8.0%, dual DPP-4i-SGLT2i add-on therapy to metformin should be considered to help more patients achieve glycemic targets. The glycemic efficacy of SGLT2i, but not DPP-4i, declines with progressive renal insufficiency. In older adults, DPP-4i maintain their tolerability and efficacy, while SGLT2i may become less efficacious due to reduced renal function, and may be associated with higher rates of volume-related adverse effects.

IMPLICATIONS: Although both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA1C , renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management.