The role of dipeptidyl peptidase 4 inhibitors in fat metabolism in patients with type 2 diabetes and obesity

Objective. 

To evaluate the influence of combined therapy of sitagliptin and metformin on fat metabolism in patients with type 2 diabetes mellitus.

Methods. 

The study included 82 patients (age, 55.3±9.1 years) with obesity and lipid metabolism disorders. None of the patients had reached their target glycated haemoglobin levels after metformin and diet therapy. Patients in group 1 (n=42) received 1.5–2-g metformin daily before the study and were switched to a formulation of 100-mg sitagliptin and 2-g metformin once a day. Patients in group 2 (n=40) were on a diet therapy before inclusion and were started on 2-g metformin/day. The following were evaluated at baseline and after 6 months of therapy: fasting glucose levels, postprandial glucose levels, glycated haemoglobin, weight, body mass index, waist circumference and lipid profile; insulin, proinsulin, leptin and adiponectin levels; insulin resistance using the homeostatic model assessment (HOMA) of β-cell function (HOMA-β) and insulin resistance (HOMA-IR). In addition, magnetic resonance imaging was performed to assess the amount of visceral fat for the total cohort.

Results. 

After 6 months, glycated haemoglobin decreased by 18.52% (p <0.001) in group 1 and by 8.17% (p <0.001) in group 2. Fasting plasma glucose and postprandial glucose levels in group 1 were reduced by 21% (p <0.001) and 26.35% (p <0.001), respectively; the corresponding reductions in group 2 were 1.45% (p >0.05) and 5.31% (p <0.05), respectively. HOMA-β increased by 33% in group 1 (p <0.001) and by 11% in group 2 (p >0.05). Adiponectin levels increased by 27.06% (p <0.001) in group 1 and by 7.16% in group 2 (p <0.001). Leptin levels were reduced by 30.47% (p <0.001) in group 1 and by 5.41% in group 2 (p <0.001). Magnetic resonance imaging showed a 7.52% reduction in visceral fat for group 1 (p <0.001) and a 1.76% reduction for group 2 (p <0.01). The comparison of subcutaneous fat dynamics did not show statistically significant differences between the groups.

Conclusion. 

Compared with metformin monotherapy, sitagliptin and metformin combination therapy had a prominent effect on non-glycaemic parameters, with more marked decreases in visceral fat and leptin and increases in adiponectin levels.

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