MD Conference Express - ENDO 2015 - (Page 17)
as playing a key role in reproductive regulation, specifically as a modulator of gonadotropin-releasing hormone
secretion [Topaloglu AK et al. Nat Genet. 2009]. The
aim of this study [NCT01872078], presented by Jyothis
T. George, PhD, University of Oxford, Oxford, United
Kingdom, was to assess the effect of the NKB receptor
antagonist, AZD4901, on LH secretion and testosterone
levels in women with PCOS.
A total of 67 women with PCOS were randomized to
receive AZD4901 20, 40, or 80 mg/day, or placebo for 28
days. All of the patients had a clinical diagnosis of PCOS
with polycystic ovarian morphology, free testosterone
(> 0.85 upper limit of normal), and oligomenorrhea. The
patients had intensive LH and testosterone sampling at
baseline (day -1), day 7, and day 28. The primary end point
was the change in 8-hour LH area under the curve (AUC)
between baseline and day 7. The secondary end points
were the change in total testosterone levels from baseline
to days 7 and 28 and in LH pulse frequency at days 7 and 28.
The LH AUC was 67.4 ± 1.6 IU/L*h at baseline and
36 ± 2.3 IU/L*h at day 7 in the AZD4901 80-mg group
compared with 61.1 ± 1.9 IU/L*h at baseline and 69.8 ±
1.7 IU/L*h at day 7 in the placebo group (a 52% reduction
relative to placebo, adjusted for baseline; 95% CI, 30% to
67%; P = .0003). LH pulse frequency was 5.8 ± 2.1 pulses/
8 hours at baseline and 3.7 ± 2.1 pulses/8 hours at
day 7 in the AZD4901 80-mg group compared with
7.2 ± 2.3 pulses/8 hours at baseline and 6.8 ± 2.6 pulses/
8 hours at day 7 in the placebo group, an adjusted mean
change of −3.55 pulses/8 hours vs placebo (P < .0001).
Total testosterone levels were 2.2 ± 1.3 nmol/L at baseline and 1.6 ± 1.5 nmol/L at day 7 in the AZD4901 80-mg
group compared with 1.5 ± 1.7 nmol/L at baseline and
1.6 ± 1.9 nmol/L at day 7 in the placebo group (a 29%
adjusted reduction relative to placebo; 95% CI, 14% to
41%; P = .0006). At day 28, testosterone was reduced by
17% in the AZD4901 80-mg group.
A post hoc analysis in the anovulatory patients, defined
as patients with serum P ≥ 6 ng/mL throughout the study,
showed that LH AUC was reduced in the ADZ4901 80-mg
group by 46% at day 7 (P = .0004) and by 35% at day 28
(P = .0203); LH pulse frequency was -3.9 pulses/8 hours at day
7 (P < .0001) and -1.89 pulses/8 hours at day 28 (P = .0205);
and testosterone was reduced by 27% at day 7 (P = .0005) and
by 20% at day 28 (P = .0111) compared with placebo.
After 7 days of treatment with AZD4901 80 mg, women
with PCOS had significant reductions in LH, LH pulse
frequency, and total testosterone. These effects persisted
for 28 days in nonovulating women. AZD4901 was safe
and well tolerated. Longer-duration studies are needed
to further evaluate its therapeutic potential, including
metabolic responses.
Improvements in Diabetes Control
Similar in Patients Who Undergo
LAGB or Intensive Management
Written by Jill Shuman
Because of advances in both the surgical and nonsurgical treatment of obesity in adults with type 2 diabetes
mellitus (T2DM), there is increasing controversy regarding the best treatment algorithm for patients who are
obese with T2DM.
The SLIMM-T2D study [NCT01073020] was a 1-year
pragmatic randomized trial within a single hospital
setting. The trial was designed to compare clinical outcomes between patients who are obese with T2DM who
underwent laparoscopic adjustable gastric band surgery
(LAGB) or Roux-en-Y gastric bypass (RYGB) and those
who participated in Why WAIT, a nonsurgical intensive
diabetes and weight loss intervention. Why WAIT incorporated intensive diet, exercise, education, and drug
modification using a multidisciplinary approach that
included a dietitian, a psychologist, a diabetes educator,
an exercise physiologist, and a physician who prescribed
medications considered weight neutral. Patients in the
Why WAIT intervention received 2 hours of instruction
per week and individualized exercise training for the first
12 weeks, with monthly one-on-one support visits for the
remainder of the 1-year follow-up.
The primary end point was the number of patients
with fasting blood sugar < 126 mg/dL and HbA1c < 6.5% at
1 year. Secondary end points included measurement of
metabolic and cardiovascular risk factors.
Data from the RYGB arm of the trial were previously published [Halperin F et al. JAMA Surg. 2014] and
showed that, compared with medical management,
RYGB produced sustained and statistically significant
improvements in HbA1c and fasting glucose (P = .03), as
Table 1. Baseline Patient Characteristics
Mean age, y
Mean weight, kg
Body mass index, kg/m2
Duration of type 2 diabetes mellitus, y
HbA1c, %
51 ± 10
109 ± 15
36.5 ± 3.7
9±5
8.2 ± 1.2
Percentage on insulin
40
Official Peer-Reviewed Highlights From ENDO 2015
17
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MD Conference Express - ENDO 2015
MD Conference Express - ENDO 2015 - (Page Cover1)
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