Effect of Add-On Therapy of Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors on Adipokines in Type 2 Diabetes Mellitus

Abid Shaheer, Ashok Kumar, Palat Menon, Mahir Jallo, Shaikh Basha


Background: Excess adiposity is associated with an increased risk of cardiovascular disease due to metabolic changes in the body. Visceral obesity increases the risk of diabetes mellitus through adipocytokines and hence the effective targeting therapies are essential to control obesity in high-risk individuals. The study’s main objective was to evaluate the effect of add-on therapy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors on visceral fat-associated serum adipokines.

Methods: The study included 90 subjects diagnosed with type 2 diabetes mellitus. The blood samples were taken before starting first-line therapy with metformin, 12 weeks after starting metformin therapy and 12 weeks after starting add-on therapy. Serum adipokines were analyzed with enzyme-linked immunosorbent assay (ELISA). Hemoglobin A1c (HbA1c) level was estimated with high-performance liquid chromatography (HPLC). The biochemical variables were measured using Cobas® 6000 analyzer.

Results: The mean adiponectin level was significantly elevated with add-on therapy using SGLT2 inhibitors and DPP4 inhibitors (P < 0.001). The mean retinol binding protein 4 (RBP4), fatty acid binding protein 4 (FABP4) and visfatin levels were reduced considerably (P < 0.001). The SGLT2 inhibitors are more effective on serum FABP4 in patients with type 2 diabetes (P = 0.038). The mean fasting plasma glucose (FPG), postprandial blood glucose (PPBG) and HbA1c levels were reduced significantly with add-on therapy (P < 0.001). Lipid profile was also altered significantly with this add-on therapy (P < 0.001).

Conclusions: The results indicate that add-on therapy exerts a beneficial effect in type 2 diabetic patients insufficiently controlled with metformin only by altering the visceral fat-associated adipokine levels and controlling the metabolic activities.

J Clin Med Res. 2021;13(6):355-362
doi: https://doi.org/10.14740/jocmr4510


Adipokines; Visceral fat; Metformin; SGLT2 inhibitors; DPP4 inhibitors

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