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

Nov 28, 2017Clinical therapeutics

Choosing DPP-4 or SGLT-2 Inhibitors Alone or Together with Metformin Depends on Patient Starting Characteristics

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Abstract

At HbA levels below 8.5%, DPP-4 inhibitors lower HbA slightly more than SGLT2 inhibitors when added to metformin.

SGLT2 inhibitors are associated with greater HbA improvements than DPP-4 inhibitors at HbA levels above 8.5%.
In patients with HbA levels at or above 8.0%, using both DPP-4 and SGLT2 inhibitors together could help more individuals reach glycemic targets.
The effectiveness of SGLT2 inhibitors declines as renal function worsens, while DPP-4 inhibitors maintain their efficacy.
Older adults may experience reduced efficacy with SGLT2 inhibitors due to declining renal function and potentially higher rates of volume-related side effects.

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PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA) targets. A major proportion of those who have not met HbAgoals have an HbA<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 HbAgoals. 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. 1C1C1C1C

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 HbAon 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. 1C

FINDINGS: At HbA<8.0% to 8.5%, HbAlowering is slightly greater with DPP-4i than with SGLT2i as an add-on to metformin; SGLT2i are associated with larger HbAimprovements than DPP-4i at higher HbAlevels. In cases of HbA≥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. 1C1C1C1C1C

IMPLICATIONS: Although both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA, renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management. 1C

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

Abstract

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