Empagliflozin is an oral selective SGLT-2 inhibitor that acts by blocking the reabsorption of glucose in the proximal tubules in the kidneys, and promotes excretion of excess glucose in the urine.
A submission for a marketing authorisation for Empagliflozin was made to the European Medicines Agency ( EMA ) in March 2013. The proposed licensed indication is for adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control. This is for use as monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom use of Metformin is considered inappropriate due to intolerance; or as add-on therapy with other glucose-lowering medicinal products including Insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. It is administered as an oral tablet once daily.
This evidence summary is based on 2 randomised controlled trials ( RCTs ) that provided published evidence evaluating Empagliflozin as combination therapy in people with type 2 diabetes.
In these 24-week trials, Empagliflozin was added to treatment with Metformin plus a sulfonylurea ( Haring et al 2013; EMPA-REG METSU trial ) or to Pioglitazone with or without Metformin ( Kovacs et al 2013; EMPA-REG PIO trial ).
A third trial has evaluated Empagliflozin as monotherapy compared with placebo or Sitagliptin for 24 weeks in people previously untreated for type 2 diabetes ( Roden et al 2013; EMPA-REG MONO trial ).
In the 2 RCTs of combination therapy, use of Empagliflozin ( 10 mg or 25 mg daily ) as add-on therapy led to additional reductions in glycated hemoglobin ( HbA1c ) levels of about 6 mmol/mol ( 0.5-0.6 percentage points ) compared with placebo.
Empagliflozin was also associated with statistically significantly greater weight loss and reductions in waist circumference ( secondary outcomes ) compared with placebo add-on therapy. Placebo-subtracted values for bodyweight reductions in the range of 1.76-1.99 kg ( p less than 0.001 ) and waist circumference decreases of 0.92-1.67 cm ( p less than or equal to 0.05 ) were reported in both trials.
Adverse events experienced by patients treated with Empagliflozin add-on therapy were mild to moderate in severity. The proportion of patients experiencing serious adverse events or adverse events leading to study drug discontinuation was low across all groups.
In the EMPA-REG METSU trial ( Haring et al 2013 ), which has compared Empagliflozin with placebo in addition to Metformin plus a sulfonylurea, there were more hypoglycaemic events in patients receiving Empagliflozin add-on treatment than in those receiving add-on placebo.
In the second RCT ( EMPA-REG PIO; Kovacs et al 2013 ), which has evaluated Empagliflozin as add-on treatment to Pioglitazone with or without Metformin, the incidence of hypoglycaemic events was similar across treatment groups. Urinary tract infections were a common adverse event; their incidence was similar in patients receiving add-on placebo ( 9-15% ) and those receiving add-on Empagliflozin ( 7-11% for both 10mg and 25mg dose ).
Currently, there are no long-term safety data and no data on the effect on Empagliflozin on the long-term complications of type 2 diabetes mellitus.
In this evidence summary, Empagliflozin was evaluated as dual therapy with Pioglitazone or triple therapy with Pioglitazone plus Metformin or Metformin plus a sulfonylurea. ( Xagena )
Fonte: NICE, 2014