Gliflozins in the Treatment of Type 2 Diabetes According to Current Recommendations SVL
Gliflozins are a relatively new group of antidiabetics with a specific mechanism of action. In addition to glycemic control, they have shown favorable effects on body weight and blood pressure, minimal risk of hypoglycemia, reduced risk of heart failure, and also renal protection and cardiovascular safety. Their position in the therapeutic algorithm for type 2 diabetes is clearly defined in the 2020 recommendations of the Society of General Medicine ČLS JEP.
Mechanism of Action of Gliflozins
Gliflozins have been part of the arsenal of Czech doctors since 2014. This group of antidiabetics includes SGLT2 inhibitors (empagliflozin, dapagliflozin, and ertugliflozin) and an SGLT1 and SGLT2 inhibitor (canagliflozin). SGLT is a sodium-glucose co-transporter, which ensures the reabsorption of glucose and sodium from the primary urine (SGLT2 about 90%, SGLT1 about 10%). In patients with type 2 diabetes, glucose reabsorption from the primary urine is increased, and they do not experience glycosuria even after exceeding the declared renal threshold for glucose. During treatment with gliflozins, the daily loss of glucose in the urine is about 70 g, which leads not only to a decrease in glycemia but also to energy losses (about 300 kcal).
Safety of Administration
The concern when administering gliflozins is the occurrence of urinary tract infections. However, in clinical studies, it was comparable to placebo. Increased mycotic infections of the external genitalia were observed, especially in women, which can be treated with antifungals without discontinuation of gliflozins. Since the efficacy of gliflozins depends on kidney function, their administration in patients with reduced renal function is guided by glomerular filtration.
Use in Clinical Practice
The mechanism of action of gliflozins is not dependent on insulin. They thus complement the effect of other antidiabetics. In addition to monotherapy, gliflozins can be administered in the following combinations in clinical practice:
- with metformin in patients inadequately compensated at the maximum tolerated dose in monotherapy;
- with sulfonylurea derivatives especially in patients inadequately compensated at the maximum dose in monotherapy, where metformin is unsuitable due to contraindication or intolerance;
- with thiazolidinediones in patients inadequately compensated;
- with gliptins;
- with GLP-1 analogues;
- with insulin or insulin analogues.
According to the current recommendations from 2020, SGLT2 inhibitors are preferred in patients treated with metformin with the presence of cardiovascular (CV) disease or a high risk of such disease, especially if heart failure or chronic kidney disease predominates, regardless of HbA1c levels. In patients without CV disease or a high risk of CV disease, gliflozins should be preferred in the event of inadequate HbA1c compensation under metformin treatment if it is necessary to minimize the risk of hypoglycemia or to limit/increase body weight.
Summary and Conclusion
In summary, the use of gliflozins in patients with DM2 is advantageous for several reasons:
- They act through a new mechanism independent of insulin, complementing the effect of other antidiabetics.
- They can be combined with practically all antidiabetics.
- They have a comprehensive metabolic effect.
- They reduce the risk of new-onset heart failure and its worsening, including hospitalizations for heart failure.
- They have significant renal protective effects.
- Empagliflozin, unlike other representatives of this drug group, has been proven to reduce overall and CV mortality in a high-risk diabetic population.
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Source: Karen I., Svačina Š. Diabetes mellitus. Novelizace 2020. Recommended Diagnostic and Therapeutic Procedures for General Practitioners. Society of General Medicine ČLS JEP, 2020. Available at: www.svl.cz/files/files/Doporucene-postupy/2020/DIABETES-MELLITUS-2020.pdf
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