Natalia Wierzbowska, Wiktoria Bosy, Bolesław Banach

Treatment of diabetes mellitus in patients with chronic kidney disease - a review of the latest research
2022-03-25

Diabetes mellitus is a civilization disease of the 21st century. Recently, there has been a significant increase in the incidence of diabetes among representatives of various social groups around the world.

Chronic hyperglycaemia can lead to diabetic complications, including functional and structural damage to the kidneys. Diabetic kidney disease develops depending on the duration of diabetes mellitus, the degree of diabetes control, and the coexistence of other factors of kidney damage. Only the cooperation between the patient with the doctor, adherence to the recommendations and regular monitoring can prevent the development of serious diabetic complications, including death.

Today, there are many modern hypoglycemic drugs with systemic benefits on the pharmaceutical market. Among them, SGLT2 inhibitors or incretin drugs (GLP-1 analogues, DPP-4 inhibitors) deserve special attention.

SGLT2 inhibitors by blocking the sodium-glucose cotransporter 2 increase the excretion of glucose in the urine, thereby lowering glycemia. The beneficial effects of flozins are observed in various tissues, including the cardiovascular system and kidneys. The use of SGLT2 inhibitors promotes nephroprotection mainly by influencing the hemodynamics of the kidneys. Recent reports point to a broad spectrum of the renal benefits of flozins. Depending on the specific drug, a delay in the sustained reduction of eGFR and a decrease in proteinuria are noted.

Incretin drugs by affecting the intestinal hormone system - GLP-1 and GIP - inhibit the increase in postprandial glycemia. The mechanism of action of GLP-1 analogs is based on binding to the receptor for endogenous glucagon-like peptide type 1, mimicking its physiological effects. The nephroprotective effect of GLP-1 analogues is manifested, in particular, by a decrease in the risk of developing or worsening persistent albuminuria. Both studies on the effectiveness of SGLT2 inhibitors and GLP-1 analogues suggest a statistically greater effect on renal parameters in patients with preserved renal function or diabetic kidney disease at an early stage of development. Studies suggest the inclusion of SGLT2 inhibitors and GLP-1 analogues in the treatment regimen of patients with type 2 diabetes as part of the early prevention of cardiovascular diseases and kidney diseases. The subject of consideration are also patients without diagnosed diabetes, for whom flozin can be a therapeutic strategy in the case of heart failure or a nephroprotection method, regardless of the initial state of the kidneys.

The mechanism of action of DPP-4 inhibitors is based on the inhibition of the enzyme dipeptidyl peptidase 4, which under normal conditions leads to a rapid inactivation of incretins. As a result, the duration of GLP-1 and GIP activity is extended, which helps to maintain normal glycemia.

No significant nephro- or cardioprotective effects were observed in studies with DPP-4 inhibitors.

It is necessary to continue research on the renal benefits of these groups of drugs, as the mechanisms of their nephroprotective action are still not fully understood. Many studies also suggest that extending the observation period may have an impact on the noticeable therapeutic effects.

Keywords: diabetes, chronic kidney disease, GLP-1 analogues, SGLT2 inhibitors, DPP-4 inhibitors.

© Farm Pol, 2022, 78 (1): 38–46