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obesity

obesity and weight management

obesity risks

  • cardiovascular disease:
    • in white Causasians, cardiovascular risk increases by 13% for every 5.2 kg/m2 increase in women and 4.3 kg/m2 in men above an optimum level of 22-23 kg/m2 and, compared to women and men with waist circumferences of 74 and 83 cm respectively, the CVD risk increased by 16% in women and 10% in men for every 12.6 cm and 11.4 cm increase in waist circumference for women and men respectively.1)
  • diabetes
  • insulin resistance
  • high sugar or fructose diet
    • small intakes of sucrose or fructose are converted to glucose by enterocytes in the small bowel which is then metabolised by the whole body as needed
    • excessive intakes of sucrose or fructose results in fructose being absorbed into the circulation and then it must be metabolised into fat primarily within the liver
  • mental health issues
  • medical iatrogenic risks

pharmacologic options

lipase inhibitors

  • orlistat

5-HT2C selective agonists

  • lorcaserin is a selective 5-HT2C agonist with 15x more activity than on 5-HT2A receptors, and 100x more activity than on 5-HT2B receptors
    • under trial for obesity management in 20102) - appears to reduce weight by ~6kg in 1 year compared with 2kg for a placebo with almost 50% of patients losing at least 5% body weight compared with only 20% of those on placebo.

other drugs which have been tried but adverse effects generally outweigh benefits

non-selective serotonin agonists

  • fenfluramine and dexfenfluramine was approved for Mx of obesity in the USA by FDA in 1973 and 1996 respectively
  • both were withdrawn in 1997 after they were found to cause serotonin associated cardiac valvulopathy which is thought to be due to agonism of 5-HT2B receptors, and is similar to that seen in carcinoid heart disease and ergot-alkaloid induced heart disease.

cannabinoid-receptor antagonists

  • rimonabant was withdrawn from the market in Europe because of an increased risk of depression, anxiety and suicidal ideation.

reuptake inhibitors

  • the serotonin and noradrenaline reuptake inhibitor, sibutramine, was removed from the European market after a 100,000 patient, 6-year SCOUT study showed an increased risk of serious nonfatal cardiovascular events such as stroke or heart attack.

surgical options

gastric laparoscopic banding (lap banding)

obesity.txt · Last modified: 2018/08/05 12:26 by gary1