Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Greenway, Frank L.; Fujioka, Ken; Plodkowski, Raymond A.; Mudaliar, Sunder; Guttadauria, Maria; Erickson, Janelle; Kim, Dennis Dong Hwan; Dunayevich, Eduardo

doi:10.1016/s0140-6736(10)60888-4

Cited by 830 publications

(614 citation statements)

References 25 publications

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“…The CP represents an anatomically and physiologically parallel region of striatum that has not previously been implicated in partner preference formation. The involvement of the opiate system in the formation of adult social attachments is of particular importance as opioid antagonists, including NTX, are being used increasingly in humans as a treatment for alcoholism, opioid dependence, obesity, and fibromyalgia (Ablin and Buskila, 2010;Anacker and Ryabinin, 2010;Greenway et al, 2010;Lobmaier et al, 2010;Soyka and Rosner, 2010). Furthermore, the role of MOR in this behavior provides a vital link between the pair bonding literature and previous literature on maternal behavior, which further supports the hypothesis that the pair bonding circuitry evolved from the same mechanisms governing maternal behavior that are present in all mammals (Donaldson and Young, 2008).…”

Section: Resultsmentioning

confidence: 99%

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

Burkett

Spiegel

Inoue

et al. 2011

Neuropsychopharmacol

112

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Despite significant evidence that opioids are involved in attachment by mediating social reward and motivation, the role of opioids in the formation of adult social attachments has not been explored. We used the socially monogamous prairie vole (Microtus ochrogaster) to explore the role of endogenous opioids in social bonding by examining partner preference formation in female prairie voles. We hypothesized that m-opioid receptors (MORs) in the striatum have a critical role in partner preference formation. We therefore predicted that peripheral administration of an opioid receptor antagonist would inhibit partner preference formation, and more specifically, that m-opioid selective receptor blockade within the striatum would inhibit partner preference formation. To test our hypotheses, we first administered the non-selective opioid antagonist naltrexone peripherally to females during an 18-h cohabitation with a male and later tested the female with a partner preference test (PPT). Females showed a dose schedule-dependent decrease in partner preference in the PPT, with females in the continuous dose group displaying stranger preferences. Next, we administered microinjections of the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) into either the nucleus accumbens shell (NAS) or the caudate-putamen (CP) immediately before a 24-h cohabitation with a male, and later tested the female with a PPT. Females receiving CTAP into the CP, but not the NAS, showed no preference in the PPT, indicating an inhibition of partner preference formation. We show here for the first time that MORs modulate partner preference formation in female prairie voles by acting in the CP.

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Section: Resultsmentioning

confidence: 99%

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

Burkett

Spiegel

Inoue

et al. 2011

Neuropsychopharmacol

112

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“…However, the expectation for weight loss effects in patients is often higher 11. Although weight‐loss drugs significantly improve cardiovascular risk factors such as insulin sensitivity, glycemic control, dyslipidemia, hypertension and chronic inflammation in patients with overweight or obesity 12, 13, 14, 15, 16, these health benefits may not be immediately obvious to patients. Also, no weight‐loss drug has been demonstrated to decrease cardiovascular morbidity or mortality 6.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States

Zhang

Manne

Jiao

2016

Obesity Science & Practice

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SummaryObjectiveTo describe the characteristics of real‐world patients potentially eligible for adjunctive pharmacotherapy for weight loss.MethodsPatients from the GE Centricity electronic medical record database were selected if they had body mass index (BMI) ≥30 or ≥27 to <30 kg m−2 with ≥1 obesity‐associated comorbidity (hypertension, dyslipidemia, or type 2 diabetes) from 2002–2011; were aged ≥18 years and had ≥12 months of continuous enrollment before and after the date of first eligible BMI recorded (index date). Descriptive statistics and logistic regression were used for analysis.ResultsOf the 1,835,541 patients with overweight or obesity included, comorbidities were common (hypertension [55.4%], dyslipidemia [36.1%] and type 2 diabetes [13.4%]). The percentage of patients who received pharmacotherapy for weight loss was 0.7% within 12 months after the index date. Patients who received pharmacotherapy had higher BMI (median, 33.6 vs. 31.3 kg m−2), were younger (median, 42 vs. 52 years), primarily women (84.3 vs. 58.2%), commercially insured (70.1 vs. 50.4%) and had more frequent use of antidepressants (30.8 vs. 14.1%) and non‐steroidal anti‐inflammatory drugs (21.7 vs. 12.0%) than those who did not at baseline (all P values < 0.0001).ConclusionsFew eligible patients received pharmacotherapy for weight loss. Patients who received pharmacotherapy tended to be heavier, younger, female, commercially insured, and used more antidepressants and non‐steroidal anti‐inflammatory drugs.

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“…Opioid receptor antagonism (naltrexone) plus proopiomelanocortin activation (bupropion) causes greater weight loss than monotherapy with either agent or placebo 95 , an effect confirmed in overweight/obese patients with comorbid T2DM, hypertension or hyperlipidaemia 96,97 . Overall, placebo-subtracted mean weight loss averaged 4.7% (range 3.2-5.2%) with naltrexone/bupropion after 1 year, with a higher proportion of patients achieving ≥5-10% weight loss and improvement of waist circumference, triglycerides, high-density lipoprotein, fasting insulin, and insulin resistance compared with placebo.…”

Section: Naltrexone Sustained Release Plus Bupropion Sustained Releasementioning

confidence: 95%

Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes

Scheen

Gaal

2014

The Lancet Diabetes & Endocrinology

175

131

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New glucose-lowering therapies, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic agents by promoting weight loss while improving glucose control. . The present review will explore the overlapping pathophysiology and also how the various therapies can, alone or in combination, combat the 'dual burden' of obesity and T2DM. Word count: 249

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Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Cited by 830 publications

References 25 publications

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States

Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes

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