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

Abstract

AimsTo investigate the pharmacodynamics, efficacy and safety of empagliflozin as adjunct to insulin in patients with type 1 diabetes.MethodsA total of 75 patients with glycated haemoglobin (HbA1c) concentrations of ≥7.5 to ≤10.5% (≥58 to ≤91 mmol/mol) were randomized to receive once‐daily empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo as adjunct to insulin for 28 days. Insulin dose was to be kept as stable as possible for 7 days then adjusted, at the investigator's discretion, to achieve optimum glycaemic control. The primary exploratory endpoint was change from baseline in 24‐h urinary glucose excretion (UGE) on day 7.ResultsEmpagliflozin significantly increased 24‐h UGE versus placebo on days 7 and 28. On day 28, adjusted mean differences with empagliflozin versus placebo in changes from baseline in: HbA1c were −0.35 to −0.49% (−3.8 to −5.4 mmol/mol; all p < 0.05 vs. placebo); total daily insulin dose −0.07 to −0.09 U/kg (all p<0.05 vs placebo); and weight were −1.5 to −1.9 kg (all p < 0.001 vs. placebo). In the placebo, empagliflozin 2.5, 10 and 25 mg groups, respectively, adverse events were reported in 94.7, 89.5, 78.9 and 100.0% of patients, and the rate of symptomatic hypoglycaemic episodes with glucose ≤3.0 mmol/l not requiring assistance was 1.0, 0.4, 0.5 and 0.8 episodes per 30 days.ConclusionsIn patients with type 1 diabetes, empagliflozin for 28 days as adjunct to insulin increased UGE, improved HbA1c and reduced weight with lower insulin doses compared with placebo and without increasing hypoglycaemia.

Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism

“…The mechanism by which SGLT2 inhibition raises LDL-C levels remains unclear. It has been suggested that the increase in LDL-C may be partly due to hemoconcentration, as SGLT2 inhibitors induce volume contraction subsequent to increased urinary volume (4,5). However, the transient diuretic effect of SGLT2 inhibitors may not completely contribute to the observed LDL-C increase.…”

Diabetic Ketoacidosis in a Patient with Type 1 Diabetes on Sodium-glucose Co-transporter-2 Inhibitors—a Case Report

“…[5][6][7][8][9][10] Use of SGLT2 inhibitors was associated with improvements in average glucose control, reduced postprandial hyperglycemia and glycemic variability, reduced body weight, and reduced insulin dose requirements. [11][12][13] Dual SGLT1/2 inhibitor, sotagliflozin, has also demonstrated significant reductions in HbA1c, postprandial glucose, weight, and insulin doses.…”

Sodium-glucose Co-transporter-2 Inhibitors in Type 1 Diabetes—a Dangerous Ally

“…The rate of symptomatic hypoglycemia or hypoglycemia requiring assistance was not increased. 17 The 24-hour mean glucose area under curve was significantly reduced, compared to placebo: adjusted mean difference was -30.2 mg/dl/h (95% confidence interval [CI] -42.2 to -18.2) with empagliflozin 10 mg and -33.0 mg/dl/h (95% CI -44.8 to -21.1) with empagliflozin 25 mg. Glucose variability was significantly decreased, time spent in target glucose range was increased and there was no increase in time spent in hypoglycemia. 18 In an 18-week, phase 2 study including 351 patients on multiple daily injections or CSII, canagliflozin was associated with decreases in HbA1c, insulin dose and body weight.…”

“…The prevalence of overweight and obesity among newly diagnosed T1D subjects was 21-22% in the [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] year age group in the Pediatric Diabetes Consortium and the SEARCH for Diabetes in Youth study. 1,2 This has been attributed to a general worldwide increase in prevalence of obesity and similar risk factors such as family history, ethnicity, and sedentary lifestyle may be contributory.…”