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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.

In patients with type 1 diabetes, empagliflozin as adjunct to insulin decreased glucose exposure and variability and increased time in glucose target range.

Background The effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD). Methods The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily reduces risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had: (i) an estimated glomerular filtration rate (eGFR) ≥20, &lt;45 mL/min/1.73m2;  or (ii) an eGFR ≥ 45, &lt;90 mL/min/1.73m2 with a urinary albumin: creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined: extra work for collaborating sites is kept to a minimum, and only essential information is collected. Results Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. Mean age at randomization was 63.8 (SD 13.9) years, 2192 (33%) were female, and 3570 (54%) had no prior history of DM. Mean eGFR was 37.5 (14.8) mL/min/1.73m2, including 5185 (78%) with an eGFR &lt; 45 mL/min/1.73m2. Median (Q1-Q3) uACR was 412 (94–1190) mg/g, with a uACR &lt; 300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease (n = 2057 [31%]), glomerular disease (n = 1669 [25%]), hypertensive/renovascular disease (n = 1445 [22%]), other (n = 808 [12%]), and unknown causes (n = 630 [10%]). Conclusions EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.