6 Possible Benefits of Adding Empagliflozin to Metformin
Currently, there is intense discussion about the advantages of sodium-glucose co-transporter 2 inhibitors (SGLT2i, also known as gliflozins) in terms of their cardio and nephroprotective properties. Below, we summarize the proven beneficial effects specifically associated with adding empagliflozin to metformin and mention the indications for empagliflozin, which are reimbursed.
Introduction
The cornerstone of pharmacotherapy for type 2 diabetes (DM2) remains metformin, but adding gliflozin, in an approved indication, can significantly benefit the patient. The use of an available fixed combination of metformin with gliflozin demonstrably increases adherence to treatment. Empagliflozin currently has reimbursement established for indications of DM2 (specializations in diabetology, endocrinology, and internal medicine) and heart failure with reduced ejection fraction (EF) ≤ 40% (specializations in cardiology, internal medicine, angiography). Details on the reimbursement conditions are available in the SÚKL database, with recommended dosages, including the necessary estimated glomerular filtration rate (eGFR) values for initiation and discontinuation, provided in the SPC.
6 Possible Benefits...
The effectiveness of adding empagliflozin to metformin was demonstrated in the randomized double-blind placebo-controlled EMPA-REG MET study, which included diabetics with glycated hemoglobin (HbA1c) levels ranging from ≥ 7 to ≤ 10% who were already on metformin. At week 24, it was found that the combination of metformin with empagliflozin (in doses of 10 or 25 mg) led to a greater reduction in HbA1c concentration compared to metformin with placebo (mean change from baseline 7.9% was -0.7%, or -0.77% vs. -0.13%), blood pressure and body weight (mean change from baseline 81.2 kg was -2.1 kg, or -2.46 vs. -0.45 kg).
Cardioprotective and nephroprotective effects of empagliflozin were also demonstrated in the well-known randomized double-blind placebo-controlled EMPA-REG OUTCOME study. Here, empagliflozin or placebo was added to standard therapy in type 2 diabetics with cardiovascular (CV) disease (74% were using metformin, 48% insulin, 43% sulfonylurea derivatives). In the empagliflozin arm, CV mortality risk was reduced by 38% compared to placebo (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.49–0.77; p < 0.001) and development or worsening of nephropathy (significant risk reduction of 39% compared to placebo); all-cause mortality was lower in the empagliflozin arm by 32% (HR 0.68; 95% CI 0.57–0.82; p < 0.001).
... and Very Good Tolerance
Patients in both studies tolerated the addition of empagliflozin very well, and the overall incidence of adverse events (AEs) was similar to that of placebo. Hypoglycemia was most commonly observed with combined treatment with sulfonylurea or insulin, but the frequency was similar in patients on empagliflozin compared to the placebo arm. The incidence of urinary tract and genital infections was slightly higher in the EMPA-REG MET study in patients on empagliflozin.
„2 in 1“ to Increase Adherence
Earlier studies have shown that fixed combinations of antidiabetics can improve patient adherence to treatment (e.g., Melikian et al., 2002), thereby increasing efficacy. Poor adherence leads to increased costs (Frois et al., EASD 2014) and is associated with higher mortality and hospitalization rates (Ho et al., 2006), whereas improved adherence is accompanied by higher therapy efficacy. For example, another previously published study (Rozenfeld et al., 2008) demonstrated that improving adherence to oral antidiabetic medication by 10% could lead to a further reduction in HbA1c level by 0.1% compared to non-adherent patients. A combination of empagliflozin with metformin (“2 in 1“) is also available in one tablet.
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Sources:
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2. Zinman B., Wanner C., Lachin J. et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes and mortality in type 2 diabetes. N Engl J Med 2015; 373 (22): 2117–2128, doi: 10.1056/NEJMoa1504720.
3. Wanner C., Inzucchi S. E., Lachin J. M. et al.; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375 (4): 323–334, doi: 10.1056/NEJMoa1515920.
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5. Frois C., Dea K., Ling D. et al. The burden of “serial non-adherence“ in patients with type 2 diabetes. Poster. 50th EASD Annual Meeting, Vienna, 2014 Sep 15–19.
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8. SPC Jardiance. Available at: www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_cs.pdf
9. Jardiance, reimbursement conditions. Available at: www.sukl.cz/modules/medication/detail.php?code=0210023&tab=prices and www.sukl.cz/modules/medication/detail.php?code=0210022&tab=prices
10. SPC Synjardy. Available at: www.ema.europa.eu/en/documents/product-information/synjardy-epar-product-information_cs.pdf
11. Synjardy, reimbursement conditions. Available at: www.sukl.cz/modules/medication/detail.php?code=0210437&tab=prices
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