Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

OBJECTIVETo investigate the efficacy and tolerability of empagliflozin as an add-on to metformin therapy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODSPatients with HbA 1c levels of ‡7% to £ 10% ( ‡53 to £86 mmol/mol) while receiving metformin ( ‡1,500 mg/day) were randomized and treated with once-daily treatment with empagliflozin 10 mg (n = 217), empagliflozin 25 mg (n = 213), or placebo (n = 207) for 24 weeks. The primary end point was the change in HbA 1c level from baseline at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24. with empagliflozin 25 mg (both P < 0.001). Empagliflozin significantly reduced MDG level and systolic and diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from baseline in weight were 20.45 kg (0.17 kg) with placebo, 22.08 kg (0.17 kg) with empagliflozin 10 mg, and 22.46 kg (0.17 kg) with empagliflozin 25 mg (both P < 0.001). Adverse events (AEs) were similar across groups (placebo 58.7%; empagliflozin 49.5-57.1%). Confirmed hypoglycemic AEs were reported in 0.5%, 1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Events consistent with urinary tract infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events consistent with genital infections were reported in 0%, 3.7%, and 4.7% of patients, respectively. CONCLUSIONSEmpagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.

Empagliflozin as adjunct to insulin in patients with type 1 diabetes: a 4‐week, randomized, placebo‐controlled trial (EASE‐1)

“…Empagliflozin has consistently been shown to lead to sustained weight loss in patients with type 2 diabetes 13, 14, 15, 16, 17, 18, including those treated with a regimen of multiple daily injections of insulin, likely due to loss of calories in the urine. The majority of weight loss in patients with type 2 diabetes is attributable to a reduction in fat mass, including reductions in both trunk fat and limb fat and in both abdominal visceral and abdominal subcutaneous adipose tissue 23.…”

“…In patients with type 2 diabetes, empagliflozin given as monotherapy or as add‐on therapy (including as add‐on to basal insulin or multiple daily injections of insulin) has consistently been shown to improve glycaemic control and reduce blood pressure and weight, with a low risk of hypoglycaemia 13, 14, 15, 16, 17, 18.…”

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes

“…Study design and entry criteria for all five trials have been published [7][8][9][10]15] (see electronic supplementary material [ESM] Methods). In four studies, patients with eGFR ≥ 30 ml min −1 1.73 m −2 were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily for 24 weeks as monotherapy or add-on therapy to background glucose-lowering medication.…”

“…In patients with type 2 diabetes, empagliflozin is consistently associated with declines in HbA 1c , systolic BP (SBP) and weight [7][8][9][10]. Empagliflozin has been shown to decrease renal hyperfiltration in patients with type 1 diabetes [11].…”

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

“…Patients underwent 24-h ABPM ≤7 days before randomization and at week 12 [27]. During the treatment period, patients continued their background BP-lowering therapy at an unchanged dose, but changes in BP-lowering medication could be initiated if a patient had a mean SBP ≥160 mmHg and/or a mean DBP ≥100 mmHg at a clinic visit.Cohort 2 comprised patients from the four pivotal trials of empagliflozin required for regulatory submissions: EMPA-REG MONO ™ [23], EMPA-REG MET ™ [24], EMPA-REG METSU ™ [25] and EMPA-REG PIO ™ [26]. Patients in these trials had T2DM, HbA1c ≥7 and ≤10% (≥53 and ≤86 mmol/mol) and a body mass index ≤45 kg/m 2 .…”