Current Recommendations for Using SGLT2 Inhibitors in Patients with Renal or Cardiovascular Risk
Type 2 diabetes mellitus (DM2) is a serious chronic metabolic disease whose prevalence has been increasing in recent years. Currently, diabetics make up approximately 8−10% of the population. The therapy is traditionally focused primarily on suppressing the development and progression of diabetic complications, but modern antidiabetics have also brought other unprecedented benefits. The following text summarizes the role of gliflozins in the pharmacotherapy of DM2 in light of current recommendations.
The Role of Gliflozins in the Pharmacotherapy of DM2
In treating DM2, it is desirable to reduce blood glucose levels, decrease body weight, and prevent microvascular and macrovascular complications. At the same time, it is necessary to minimize the risk of hypoglycemia. The first-line drug is metformin, mainly due to its ease of use and cost-effectiveness. However, metformin in monotherapy may not maintain the desired compensation of glucose levels in the long term, and therefore, its combination with other antidiabetics may be necessary. For some patients, the use of metformin may also be contraindicated or intolerable. In such situations, newer groups of drugs that have entered diabetes treatment can be used according to recommendations. The newest class of antidiabetics is the sodium-glucose co-transporter type 2 (SGLT2) inhibitors, or gliflozins.
Gliflozins block SGLT2 glucose transporters, preventing the reabsorption of glucose in the proximal renal tubules. The result is glycosuria, which leads to a reduction in blood glucose levels and an energy deficit. The higher the blood glucose level, the greater the antidiabetic effect of gliflozins. The risk of hypoglycemia is therefore very low with the use of these drugs. Due to their mechanism of action, gliflozins can be advantageously combined with all other antidiabetics. They have a complex metabolic effect and reduce the risk of heart failure. A decrease in blood pressure is also often recorded. In addition, empagliflozin has been shown to reduce overall and cardiovascular mortality.
New Recommendations for Gliflozin Treatment
Based on the results of large randomized studies and data from real clinical practice, representatives of Czech professional societies have formulated applicable recommendations in clinical practice, aiming to define groups of patients who will benefit the most from the use of gliflozins in the early stages of diabetes treatment. The first-line drug remains metformin for practical reasons if the patient tolerates it and it is not contraindicated. The second-line therapy, according to the recommendations, regardless of the values of glycated hemoglobin (HbA1c), includes the following drugs:
- For patients at high cardiovascular risk (defined according to the 2019 ESC guidelines): SGLT2 inhibitors or glucagon-like peptide 1 (GLP-1) agonists.
- For patients with existing heart failure (defined according to the 2016 ESC guidelines): SGLT2 inhibitors.
- For patients with impaired renal function:
- eGFR < 1.5 ml/s or albuminuria (> 30 mg/24 hours or albumin/creatinine ratio > 3 mg/mmol): SGLT2 inhibitors.
- eGFR < 1.5 ml/s along with macroalbuminuria (> 300 mg/24 hours or albumin/creatinine ratio > 30 mg/mmol) even with adequate diabetes control with metformin in combination with another antidiabetic: it is advisable to replace this second drug with a preparation containing an SGLT2 inhibitor.
If eGFR drops below 0.5 ml/s, SGLT2 inhibitor treatment should be discontinued due to a lack of data on their safety and efficacy. Additionally, their effect cannot fully develop in reduced glomerular filtration. Possible side effects of gliflozins include polyuria, orthostatic hypotension, and genital yeast infections (more common in women).
Conclusion
New recommendations from professional societies provide physicians with clarified information on the use of new drug groups in the treatment of type 2 diabetes. The success of treatment also depends on patient cooperation in maintaining a healthy lifestyle and therapeutic plan. Every patient must be carefully educated on the important principles of treatment, complication prevention, the need for regular check-ups, and self-monitoring of blood glucose levels. Without adhering to these conditions, the therapy may not be successful despite the best efforts of the attending physician.
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Sources:
1. Škrha J., Prázný M., Haluzík M. et al. Recommendations for the use of SGLT2 inhibitors in patients with cardiovascular and renal risk. Acta Medicinae 2020; 9 (1−2): 35.
2. Švihovec J., Bultas J. Pharmacology. Grada, Prague, 2018.
3. Karen I., Svačina Š. Diabetes mellitus. Novelization 2020. Recommended diagnostic and therapeutic procedures for general practitioners. Society of General Medicine CLS JEP, 2020. Available at: www.svl.cz/files/files/Doporucene-postupy/2020/DIABETES-MELLITUS-2020.pdf
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