correlations observed between LF and fasting insulin (r = 0.54,
p < 0.0001). Fasting glucose correlated positively with both
VLDL1-TG production rate (r = 0.41, p = 0.002) and pool size
(r = 0.33, p = 0.013).
Conclusions: Weight loss achieved by simple means in routine
primary care brought about a striking decrease in liver fat content,
with decreased VLDL1-TG production rate and pool size. The
associated three-fold decrease in plasma insulin reﬂects a re-
establishment of normal hepatic insulin sensitivity.
Severe hypoglycaemia, cardiovascular
outcomes and death: Experience from the
‘Liraglutide Effect and Action in Diabetes:
Evaluation of Cardiovascular Outcome
Results’ (LEADER) trial
, B Zinman
, SP Marso
, E Christiansen
, S Calanna
and JB Buse
School of Medicine, University of Swansea, Swansea, UK,
Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto,
Research Medical Center, Kansas City, Missouri, USA,
Novo Nordisk A/S, Søborg, Denmark,
University of North Carolina School of
Medicine, Chapel Hill, North Carolina, USA
Aims: In the LEADER cardiovascular (CV) outcomes trial
(N = 9,340; NCT01179048), the risk of both CV events and
hypoglycaemia was reduced with liraglutide treatment vs placebo,
when added to standard of care, in patients with Type 2 diabetes and
high risk for CV disease. This post hoc analysis examines potential
associationsbetweensevere hypoglycaemiaand CV eventsanddeath.
Methods: We analysed time to ﬁrst major adverse cardiovascular
event ([MACE] CV death, non-fatal myocardial infarction or non-
fatal stroke), CV death and all-cause death, comparing patients
with/without severe hypoglycaemia, and adjusted for different
periods of follow-up and randomised treatment (time-dependent
covariate Cox regression).
Results: A total of 267 patients experienced severe hypoglycaemia
(liraglutide n = 114, placebo n = 153; rate ratio 0.69; 95%
conﬁdence interval [CI] 0.51 to 0.93) and were more likely than
those without severe hypoglycaemia to experience MACE (hazard
ratio [HR] 2.2; 95% CI 1.6 to 3.0; p < 0.0001), CV death (HR
3.7; 95% CI 2.6 to 5.4; p < 0.0001), and all-cause death (HR 3.6;
95% CI 2.7 to 4.9; p < 0.0001), with a higher risk up to 60 days
after the hypoglycaemic episode, irrespective of treatment group.
The protective effect of liraglutide on risk of MACE was
unchanged when patients with severe hypoglycaemia were
excluded from the analysis (patients with severe hypoglycaemia
accounted for 5% of all MACE in the trial).
Conclusions: Patients experiencing severe hypoglycaemia were at
greater risk of CV events and death, particularly early after the
hypoglycaemic episode. Reducing severe hypoglycaemia remains a
cornerstone of diabetes management.
Does baseline HbA1c or change in HbA1c
predict the reduction in cardiovascular
death with empagliﬂozin? Results from
, D Fitchett
, C Wanner
, M Mattheus
, HJ Woerle
and B Zinman
Section of Endocrinology, Yale University School of Medicine, New Haven,
Division of Cardiology, St Michael’s Hospital, University of Toronto,
Department of Medicine, W
urzburg University Clinic,
Therapeutic Area Metabolism, Boehringer Ingelheim
Pharma GmbH & Co. KG, Ingelheim, Germany,
Research Institute, Mount Sinai Hospital, Toronto, Canada
Aims: In the EMPA-REG OUTCOME trial, empagliﬂozin
reduced cardiovascular (CV) death by 38% vs placebo (hazard
ratio, HR, 0.62; 95% conﬁdence interval, CI, 0.49, 0.77) in
patients with Type 2 diabetes and established CV disease. We
investigated whether baseline HbA1c or change in HbA1c inﬂu-
enced the reduction in CV death.
Methods: Patients were randomised to empagliﬂozin 10mg,
empagliﬂozin 25mg or placebo in addition to standard of care.
Background glucose-lowering therapy was to remain unchanged
for 12 weeks and then be adjusted to achieve glycaemic control
according to local guidelines. CV death was analysed in the pooled
empagliﬂozin group vs placebo in subgroups by baseline HbA1c
and reduction from baseline in HbA1c at week 12 using a Cox
proportional hazards model.
Results: In total, 7,020 patients were treated. Median observation
time was 3.1 years. In subgroups by baseline HbA1c <7.0%, 7.0 to
<8.0%, 8.0 to <9.0%, and ≥9.0%, HRs (95% CI) for CV death with
empagliﬂozin vs placebo were 0.30 (0.12, 0.80), 0.59 (0.42, 0.83),
0.67 (0.45, 0.99), and 0.76 (0.44, 1.31), respectively (p = 0.4104 for
treatment by subgroup interaction). In subgroups by change from
baseline in HbA1c at week 12, HRs (95% CI) for CV death after
week 12 with empagliﬂozin vs placebo were 0.57 (0.37, 0.88) in
patients with a reduction of ≥0.5% and 0.75 (0.75, 1.00) in patients
with a reduction of <0.5% (p = 0.2853 for interaction).
Conclusion: In the EMPA-REG OUTCOME trial, the reduction
in CV death with empagliﬂozin appeared to occur irrespective of
baseline HbA1c or the early glycaemic response.
Abstracts of the Diabetes UK Professional Conference, 14–16 March 2018 DIABETICMedicine
ª 2018 The Authors, presented at the Diabetes UK Professional Conference ª 2018 Diabetes UK. 35 (Suppl. 1), 5–35