Diabetes Metab J.  2019 Apr;43(2):158-173. 10.4093/dmj.2018.0057.

Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors

• Lee JY
• Cho Y
• Lee M
• Kim YJ
• Lee YH
• Lee BW
• Cha BS
• Kang ES

• KMID: 2442769
• DOI: http://doi.org/10.4093/dmj.2018.0057

Abstract

BACKGROUND
We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM).
METHODS
A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications.
RESULTS
After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome.
CONCLUSION
A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

Keyword

Blood glucose; Diabetes mellitus, type 2; Glycated hemoglobin A; Sodium-glucose transporter 2 inhibitors

MeSH Terms

Blood Glucose
Body Mass Index
Diabetes Mellitus, Type 2
Dipeptidyl Peptidase 4
Glomerular Filtration Rate
Hemoglobin A, Glycosylated
Humans
Metformin
Multivariate Analysis
Blood Glucose
Dipeptidyl Peptidase 4
Metformin

Figure

• 

  Fig. 1 Efficacy parameters according to baseline glycosylated hemoglobin (HbA1c) and body mass index (BMI). (A) Change from baseline HbA1c, (B) changes in body weight according to baseline HbA1c and BMI categories. Data are expressed as median (interquartile range). aP<0.01, bP<0.001.

• 

  Fig. 2 Efficacy parameters according to baseline anti-diabetic drug use. (A) Change from baseline glycosylated hemoglobin (HbA1c), (B) subjects with baseline HbA1c ≥7% who achieved HbA1c <7%, (C) changes in body weight. Data are expressed as median (interquartile range) or number (%). DPP4i, dipeptidyl peptidase 4 inhibitor; TZD, thiazolidinedione. aP<0.05.

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