The fixed-dose combination of alogliptin and pioglitazone in the treatment of type 2 diabetes mellitus: a natural path to triumph

Diabetes mellitus is a progressive disease, so the choice of therapy determines the long-term prognosis of patients’ quality of life. According to real-world clinical practice, only approximately 50% of patients achieve the target HbA1c level of less than 7.0%. Treatment algorithms for type 2 diabetes mellitus (DM2) suggest the early administration of a rational combination of hypoglycemic agents. Pioglitazone (PIO), a thiazolidinedione, reduces insulin resistance and potentiates insulin-mediated glucose uptake in peripheral tissues, while alogliptin (ALO), a dipeptidyl peptidase-4 inhibitor, enhances glucose-stimulated insulin secretion from pancreatic β-cells by increasing serum incretin levels. Thus, the fixed-dose, complementary combination of these two drugs, which have proven glucose-lowering efficacy and safety, appears to be a promising approach for stabilizing glucose homeostasis, improving glycemic control and addressing other pathogenic factors in DM2 patients, while offering a convenient dosing regimen. The introduction of the fixed-dose combination of PIO and ALO into clinical practice provides new impetus for the treatment of patients with both newly diagnosed and untreated long-standing diabetes. The superiority of combination therapy with these drugs over either drug alone has been confirmed, while simultaneously mitigating side effects. Numerous studies have confirmed and laid the foundation for the clinical implementation of the Russian drug Incresync, a fixed-dose combination of ALO and PIO. The Prosperity trial, conducted at 52 centers across the Russian Federation over a three-year period, enrolled 1,999 patients with newly diagnosed DM2 or those who had inadequate glycemic control with previous therapy. The results demonstrated the pleiotropic effect of the ALO and PIO combination, which improved not only glycemic control but also lipid metabolism, reducing total cholesterol, triglycerides, low-density lipoproteins, and blood pressure, confirming the drug’s cardiovascular safety. Incresync also resulted in reduced body weight and waist circumference, body mass index, and insulin resistance. The study confirmed the safety of this medication in terms of renal function: a decrease in albuminuria was recorded while the glomerular filtration rate remained intact, indicating the nephroprotective properties of the combination. Incresync demonstrated not only high efficacy and safety but also high patient compliance and satisfaction with treatment. Although belonging to different classes of hypoglycemic agents, both components exhibit additive effects on various pathogenetic mechanisms of diabetes, have a low risk of hypoglycemia, and can be recommended for various groups of DM2 patients.