Page 470 - fbkCardioDiabetes_2017

446 Obesity- Pharmacotherapy

ER topiramate treatment arms (15 mg and 7.5 mg) −1.2%). More NB32-treated participants (P < 0.001)
and one placebo arm were initiated in conjunction experienced ≥5% weight loss versus placebo at week
with a 500 kcal/day dietary deficit (74). After 1 year 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%).
of treatment, a reduction in body weight of 12.4% with The most frequent adverse effect reported include
phentermine 15.0 mg plus topiramate 92.0 mg and nausea, headache, constipation, dizziness,

9.6% with phentermine 7.5 mg plus topiramate 46.0 vomiting, insomnia and dry mouth, and the drug
mg, compared with 1.6% in the placebo group was is contraindicated in patients with seizure history.
reported. Cardiovascular improvements were also A Multicentre, Randomized, Double-Blind, Placebo-
observed.
Controlled Study Assessing the Occurrence of
EQUIP trial similarly designed comprised two Major Adverse Cardiovascular Events (MACE) in
phentermine/ER topiramate treatment arms (15 mg Overweight and Obese Subjects With Cardiovascular
and 3.75 mg) and a placebo arm (14). From a mean Risk Factors Receiving Naltrexone SR/Bupropion SR
baseline body weight of 115.2–118.5 kg, the majority [LIGHT study] to address long term cardiovascular
of subjects (67%) in the 15 mg group lost at least 5% risk, which was due to reach completion in 2017.
of baseline body weight and 47% lost at least 10% of An interim analysis of 25% of the enrolled patients
body weight from baseline. In the 3.75 mg group, the showing a reduction in the number of cardiovascular
corresponding proportions of patients achieving 5% events in the naltrexone/bupropion arm. Based on
and 10% body weight loss from baseline were 45% this the FDA approved naltrexone/bupropion in
and 19%, respectively. Minimal improvements were September 2014, with the requirement for ongoing
reported in cardiovascular markers such as blood post-marketing studies.
pressure and lipid profiles.
Liraglutide
SEQUEL study, a 2-year extension trial of CONQUER,
has been performed, which confirmed the consistency Liraglutide, an analogue of human glucagon-like
and durability of the CONQUER findings. Moreover, peptide (GLP)-1, has a half- life of 13 h, which greatly
a 76% reduction in new-onset T2D in the maximum extends its activation of the GLP-1 receptor (the half-
dose group was observed. life of native GLP-1 is ~1.5 min), thereby increasing
stimulation of glucose-dependent insulin secretion
Pregnancy is a contraindication due to the topiramate- and glucagon suppression. Liraglutide Effect and
related increased risk of orofacial clefts; It is also Action in Diabetes (LEAD) trial demonstrated
contraindicated in hyperthyroidism glaucoma, most consistent efficacy in reducing HbA and fasting
1c
common adverse effect to phentermine/topiramate in plasma glucose, leading to its approval (at doses up
these trials were paraesthesia dizziness, dysgeusia, to 1.8 mg daily) for management of glycaemic control
insomnia, constipation and dry mouth, with no in adults with T2D FDA in 2010.
increased risk of severe cardiovascular events.
Native GLP-1 has regulates appetite and feeding
Naltrexone/Bupropion centers in the brain; and it has, potential to impact
upon energy intake, most likely mediated by reducing
Bupropion is a relative weak inhibitor of norepinephrine appetite and decreasing food intake, as measured by
and dopamine uptake, it stimulates hypothalamic appetite scores and post-prandial satiety and fullness
proopiomelanocortin (POMC) neurons, leading ratings, and did not increase energy expenditure.
to melanocortin receptor activation [MCR4] and
induction of weight loss via appetite suppression and Liraglutide (3.0 mg daily), in higher doses was tested
increased energy expenditure. Naltrexone is opioid in phase III clinical trials (the SCALE programme) to
receptor antagonist that would normally induce a investigate the safety and efficacy of liraglutide 3.0
negative feedback-mediated repression of POMC mg in weight management in obese patients both
activation, and thus acts synergistically to prolong with and without T2D.
the action of bupropion on metabolism. Phase III trials SCALE study, the Obesity and Prediabetes trial,
have been completed in diabetic and nondiabetic investigated the effects of liraglutide 3.0mg in 3731
patients (Contrave Obesity Research [COR]-I, COR-II, individuals with BMI ≥ 30 kg/m 2 or 27 kg/m 2 with
COR-Intensive Behaviour Modification [BMOD] and additional comorbidities, with or without prediabetes,
COR-Diabetes trials). In COR-II Significant (P < 0.001) over 56 weeks (97). At week 56, individuals on
greater weight loss was observed with NB32 (32 mg liraglutide 3.0 mg had lost 8.0% (8.4 kg) of body weight
naltrexone and 360 mg bupropion) versus placebo compared with 2.6% (2.8 kg) on placebo [estimated
at week 28 (−6.5% vs. −1.9%) and week 56 (−6.4% vs.
treatment difference 5.4%, (5.6 kg), p < 0.001]. A

GCDC 2017