PracticeUpdate: Endocrinology

CONFERENCE COVERAGE

4

52nd annual meeting of the European Association for the Study of Diabetes 12–16 SEPTEMBER 2016 • MUNICH, GERMANY

Myocardial dysfunction in diabetes, pregnancy outcomes of women with

gestational diabetes, keeping HbA1c at goal, and overuse of acetylsalicylic acid in diabetes were just a handful of the many scientific and clinical presentations at the 52nd annual meeting of the European Association for the Study of Diabetes (EASD). The PracticeUpdate Editorial Team reports.

Though liraglutide + insulin is effective in type 1 diabetes, a high hypoglycaemia rate limits its use Liraglutide 1.8 and 1.2 mg, as an adjunct to insulin, has been shown to lead to greater reductions in haemoglobin A1c, body weight, and total insulin dose than placebo. Higher rates of symptomatic hypoglycaemia limit its utility for a broad population of patients with type 1 diabetes, however. T his outcome of ADJUNCT ONETM, a 52-week double-blind, multinational treat-to-target trial in adults with type A1c were significantly larger for liraglutide 1.8 and 1.2 mg than for placebo (estimated treatment differences 95% CI 1.8 mg: –0.20% [–0.32; –0.07], 1.2 mg: –0.15% [–0.27; –0.03], 0.6 mg: –0.09% [–0.21; 0.03]).

1.8 mg: 1.31 [1.07; 1.59], 1.2 mg: 1.27 [1.03; 1.55], 0.6 mg: 1.17 [0.97; 1.43]). No significant differences were observed for severe hypoglycaemic episodes (1.8 mg [45], 1.2 mg [31], 0.6 mg [40], placebo [57]). Sig- nificantly more hyperglycaemic episodes with ketosis >1.5 mmoL/L were seen with 1.8 mg [77] than for placebo [37], but not for 1.2 mg [44] or 0.6 mg [54]. Eight diabetic ketoacido- sis episodes occurred (1.8 mg [3], 1.2 mg [1], 0.6 mg [4], placebo [0]). The most frequently reported adverse events with liraglutide were nausea and vomiting. Dr Mathieu concluded that liraglutide 1.8 and 1.2 mg, as an adjunct to insulin, led to greater reductions in haemoglobin A1c, body weight, and total insulin dose than placebo. Higher rates of symptomatic hypoglycaemia limit its clinical utility for a broad population of patients with type 1 diabetes, however. She added, “There might still be a role for glucagon-like peptide 1 receptor agonists as adjunct therapies in people with type 1 dia- betes. In real life, the benefits on weight and haemoglobin A1c outweigh the risk of hypo- glycaemia. And in real life, doses of insulin can be adapted more rapidly to glycaemia than in a clinical trial.”

At baseline, mean age, type 1 diabetes duration, haemoglobin A1c, and body weight were 44 years, 21 years, 8.2%, and 86.2 kg, respectively. Fifty-two percent of subjects were women, 28% were on continuous subcutane- ous insulin treatment, 7% had severe hypogly- caemia in the past year, 6% had hypoglycaemic unawareness, and 17% had a fasting C-peptide ≥ 0.03 nmoL/L. HaemoglobinA1c was reduced 0.34–0.54% across groups at week 52. Despite the treat- to-target design, reductions in haemoglobin The benefits on weight and haemoglobin A1c outweigh the risk of hypoglycaemia. And in real life, doses of insulin can be adapted more rapidly to glycaemia than in a clinical trial.

1 diabetes in suboptimal glycaemic control (haemoglobinA1c 7–10%) was reported at the EASD 2016 meeting. Chantal Mathieu, MD, of Katholieke Uni- versiteit, Leuven, Belgium, and colleagues set out to determine whether adjunct treatment with liraglutide, a glucagon-like peptide-1 analog, improves glycaemic control and re- duces insulin requirements and body weight in type 1 diabetes. Subjects (n = 1398) were randomised 3:1 to once-daily subcutaneous injections of lira- glutide (1.8, 1.2, or 0.6 mg) or placebo as an adjunct to insulin. Primary endpoints were change in haemoglobin A1c, fasting body weight, and total insulin dose. The secondary endpoint was the incidence of symptomatic hypoglycaemic episodes.

Reductions in body weight were significantly larger for all liraglutide groups than for placebo (estimated treatment differences and 95% CI 1.8 mg: –4.9 kg [–5.7; –4.2], 1.2 mg: –3.6 kg [–4.3; –2.8], 0.6 mg: –2.2 kg [–2.9; –1.5]). Reductions in total insulin dose were sig- nificantly larger for liraglutide 1.8 and 1.2 mg than for placebo (estimated treatment ratios and 95% confidence intervals 1.8 mg: 0.92 [0.88; 0.96], 1.2 mg: 0.95 (0.91; 0.99), 0.6 mg: 1.00 [0.96; 1.04]). Significantly more symptomatic hypogly- cemic episodes (severe or plasma glucose <56 mg/dL and hypoglycaemic symptoms) were seen for liraglutide 1.8 and 1.2 mg than for placebo (estimated rate ratios and 95% CI

PRACTICEUPDATE ENDOCRINOLOGY