Combination therapy for obesity

2017 ◽  
Vol 31 (11) ◽  
pp. 1503-1508 ◽  
Author(s):  
John PH Wilding
Keyword(s):  
Bariatric Surgery ◽  
Combination Therapy ◽  
Low Dose ◽  
Lifestyle Modification ◽  
Gut Hormones ◽  
First Line ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
High Doses

Obesity is a chronic disease with serious consequences and although lifestyle modification is considered first line treatment, it is often ineffective, especially in the long term. Relatively few people with obesity will undergo the most effective currently available treatment of bariatric surgery. Pharmacotherapy can bridge the gap between lifestyle modification and surgery, but many monotherapies have only modest efficacy or require high doses with unacceptable side effects. As with many other areas of medicine, combination therapy is now becoming accepted as a way of optimising efficacy for weight management, whilst minimising adverse effects. Combinations may use different medications with complementary modes of action. Currently available combination therapies are low-dose phentermine and sustained release topiramate and naltrexone/bupropion. Many other possibilities exist and promising options include combination of phentermine with a sodium glucose co-transporter 2 inhibitor or combination of a glucagon-like peptide 1 agonist with other gut hormones or with a sodium glucose co-transporter 2 inhibitor. The ultimate aim is to match the efficacy of bariatric surgery with a combination of medicines, but this remains an elusive goal.

GLP-1: A Mediator of the Beneficial Metabolic Effects of Bariatric Surgery?

Physiology ◽  
2015 ◽  
Vol 30 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Sean Manning ◽  
Andrea Pucci ◽  
Rachel L. Batterham
Keyword(s):  
Bariatric Surgery ◽  
Gastric Bypass ◽  
Sleeve Gastrectomy ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Physiological Changes ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

There has been increasing interest in the role that gut hormones may play in contributing to the physiological changes produced by certain bariatric procedures, such as Roux-en-Y gastric bypass and sleeve gastrectomy. Here, we review the evidence implicating one such gut hormone, glucagon-like peptide-1, as a mediator of the metabolic benefits of these two procedures.

scholarly journals The Gut Hormones in Appetite Regulation

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Keisuke Suzuki ◽  
Channa N. Jayasena ◽  
Stephen R. Bloom
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Food Intake ◽  
Peptide Yy ◽  
Critical Role ◽  
Gut Hormones ◽  
Energy Status ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight.

Effect of bariatric surgery on serum glucagon like peptide-1 concentration and metabolic parameters among obese type 2 diabetics

2013 ◽  
Author(s):  
Salah El Din Shelbaya ◽  
Alaa Abbas Mostafa ◽  
Salwa Seddik ◽  
Manal M. Abu Shady ◽  
Meram M. Bekhet ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Metabolic Parameters ◽  
Type 2 Diabetics ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Efficacy of dapagliflozin in combination therapy with the glucagon-like peptide-1 analog in obese patients with type 2 diabetes

2015 ◽  
Vol 2 (e1) ◽  
pp. 008-008
Author(s):  
Momoko Isono ◽  
Kazuya Fujihara ◽  
Shoko Furukawa ◽  
Ryo Kumagai ◽  
Hiroaki Yagyu
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Obese Patients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

2007 ◽  
Vol 292 (5) ◽  
pp. G1359-G1365 ◽  
Author(s):  
Christopher N. Andrews ◽  
Adil E. Bharucha ◽  
Michael Camilleri ◽  
Phillip A. Low ◽  
Barbara Seide ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
High Dose ◽  
Double Blind Study ◽  
Vagal Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor NG-monomethyl-l-arginine acetate (l-NMMA; 4 mg·kg−1·h−1) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of l-NMMA (10 mg/kg bolus plus 8 mg·kg−1·h−1 infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by 99mTc-single-photon-emission computed tomography imaging. GLP-1 increased ( P = 0.04) fasting gastric volume by 83 ± 16 ml (vs. 17 ± 11 ml for placebo) and augmented ( P ≤ 0.01) postprandial accommodation by 688 ± 165 ml (vs. 542 ± 29 ml for placebo). l-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. l-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, l-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 ± 37 ml, P ≤ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

scholarly journals Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term insulin resistance

2015 ◽  
Vol 593 (9) ◽  
pp. 2185-2198 ◽  
Author(s):  
Kim A. Sjøberg ◽  
Stephen Rattigan ◽  
Jacob F. Jeppesen ◽  
Anne-Marie Lundsgaard ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Differential Effects ◽  
Short And Long Term ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Microvascular Recruitment

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

1995 ◽  
Vol 73 (9) ◽  
pp. 1609-1619 ◽  
Author(s):  
S. L. Monfort ◽  
J. L. Brown ◽  
T. C. Wood ◽  
M. Bush ◽  
L. R. Williamson ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Fertile Period ◽  
Nonbreeding Season ◽  
Testosterone Secretion ◽  
High Doses ◽  
Seasonal Decline ◽  
Seasonally Breeding

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

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