Jardiance (empagliflozin) is indicated for type II diabetes inadequately controlled by diet and exercise, either as monotherapy when metformin is not tolerated or in combination with other hypoglycaemic agents (including insulin) when these alone provide inadequate glycaemic control.1
Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that prevents glucose reuptake in the kidney, leading to the excretion of excess glucose in the urine. The mechanism of action is non-insulin-dependent, thus contributing to a low risk of hypoglycaemia.1
The efficacy and safety of empagliflozin for the treatment of type II diabetes were assessed in 10 double-blind, placebo- and active-controlled clinical trials (n=11,250) in the EMPA-REG study programme. Investigators evaluated once-daily empagliflozin at doses of 10mg and 25mg in patients with inadequate glycaemic control. Four studies lasted 24 weeks and patients were treated with empagliflozin for up to 102 weeks in extensions of these and other studies.1
Monotherapy (EMPA-REG MONO study)
Investigators compared empagliflozin monotherapy to placebo and sitagliptin monotherapy (100mg once daily) in 899 patients who had not received oral or injected anti-diabetes treatment in the previous 12 weeks. At week 24, the adjusted mean differences in change from baseline HbA1c compared with placebo were -0.74% for empagliflozin 10mg, -0.85% for empagliflozin 25mg and -0.73% for sitagliptin (p<0.0001 for all).2
Add-on to metformin (EMPA-REG MET and EMPA-REG METSU)
When added to metformin in patients with inadequate glycaemic control on monotherapy (n=637), empagliflozin produced significant decreases in adjusted mean HbA1c change from baseline at week 24 compared with placebo: -0.70% for empagliflozin 10mg and -0.77% for empagliflozin 25mg, versus -0.13% for placebo (p<0.001 for both comparisons).3 Empagliflozin at either dose added to a regimen containing metformin and a sulfonylurea (n=666) also provided significant benefits over placebo at week 24, with similar reductions in HbA1c to those observed in the EMPA-REG MET study.4
Add-on to pioglitazone or pioglitazone plus metformin (EMPA-REG PIO)
Patients (n=498) with inadequate glycaemic control on pioglitazone (at least 30mg daily), with or without concomitant metformin (at least 1.5g daily), had empagliflozin added to their treatment regimen. A significantly greater reduction in baseline HbA1c was observed in the empagliflozin 10mg group (-0.6%) and 25mg group (-0.7%) compared with the placebo group (-0.1%) after 24 weeks of treatment (p<0.001 for both).5
Head to head vs glimepiride (EMPA-REG H2H-SU)
In a direct comparison study (n=1,549), empagliflozin 25mg was non-inferior to glimepiride (1–4mg once daily) when added to metformin in patients with inadequate glycaemic control. The adjusted mean difference in change from baseline HbA1c values with empagliflozin versus glimepiride was -0.11% (p=0.0153 for superiority).6
Add-on to basal insulin (EMPA-REG BASAL)
The EMPA-REG BASAL study included 494 patients taking stable basal insulin glargine or insulin detemir (≥20 units/day) or isophane insulin (≥14 units/day), with or without metformin and/or sulfonylurea. The basal insulin dose remained fixed for the first 18 weeks but was adjusted at investigator discretion during the following 60 weeks if fasting plasma glucose exceeded 110mg/dL.7 At week 18, the adjusted mean change in HbA1c from baseline compared with placebo was -0.6% in patients receiving empagliflozin 10mg and -0.7% in patients receiving empagliflozin 25mg (p<0.001 for both). These reductions were sustained until study end at 78 weeks.7
Add-on to multiple daily injections of insulin (EMPA-REG MDI)
The efficacy and safety of empagliflozin were assessed in obese patients receiving fixed multiple daily injections of insulin (n=563). The adjusted mean change from baseline HbA1c at week 18 was -0.94% and -1.02% for the 10mg and 25mg doses, respectively, against -0.50% for placebo (both p<0.001).8
Secondary endpoint benefits
Empagliflozin produced clinically meaningful reductions in fasting plasma glucose, body weight, and systolic and diastolic blood pressure compared with placebo.1
Hypoglycaemia occurred more commonly when empagliflozin was used in combination with an insulin or a sulfonylurea; prescribers should consider reducing the dose of insulin or sulfonylurea when adding empagliflozin to these agents. As with other SGLT2 inhibitors, there was an increased incidence of genital and urinary tract infections in patients taking empagliflozin, likely to be caused by the induced glycosuria.1
- Jardiance Summary of Product Characteristics, June 2014.
- Roden M et al. Lancet Diabetes Endocrinol 2013; 1: 208–19.
- Haring HU et al. Diabetes Care 2014; 37: 1650–9.
- Haring HU et al. Diabetes Care 2013; 36: 3396–404.
- Kovacs CS et al. Diabetes Obes Metab 2014; 16: 147–58.
- Ridderstrale M et al. Lancet Diabetes Endocrinol 2014; 2: 691–700.
- Rosenstock J et al. Poster presented at EASD, Barcelona, Spain, September 2013; P931.
- Rosenstock J et al. Diabetes Care 2014; 37: 1815–23.
Further information: Boehringer Ingelheim