Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78‐week randomized, double‐blind, placebo‐controlled trial

Abstract

Aims:To investigate the efficacy and tolerability of empagliflozin added to basal insulin-treated type 2 diabetes. Methods: Patients inadequately controlled [glycated haemoglobin (HbA1c) >7 to ≤10% (>53 to ≤86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n = 169), empagliflozin 25 mg (n = 155) or placebo (n = 170) for 78 weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m 2 ]. The basal insulin dose was to remain constant for 18 weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78.Results: At week 18, the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1% (−0.1 ± 0.8 mmol/mol) for placebo, compared with −0.6 ± 0.1% (−6.2 ± 0.8 mmol/mol) and −0.7 ± 0.1% (−7.8 ± 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p < 0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p < 0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p = 0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35-36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively. Conclusions:Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

“…110 However, in the EMPA-REG BASAL (Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin) study, which enrolled patients with type 2 diabetes with BMI ≤ 45 kg/m 2 , inadequately controlled (HbA 1c > 7% to ≤ 10%), despite treatment with basal glargine or detemir insulin (≥ 20 IU/day) or NPH insulin (≥ 14 IU/day), with or without metformin and/or sulfonylurea use, Rosenstock et al 111 observed that both UTIs as well as GTIs were more frequent in the empagliflozin groups than with the placebo group.…”

Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials

“…1), totalling 15,309 unique participants [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated.…”

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.…”