CHUBBY OR FAT??

Hello Bloggers & Friends!
I am Back!!
After a small break here i start again with my blog posts.. When i was trying to decide on the topic to blog about there were various options. But, i wanted this blog post to be special as its coming after a break.. 
Finally decided on two special topics
1- Obesity drugs
2- Artificial pancreas.
Guess who won??
Go on reading!
Hope you find it useful!





India, once known for its indigenous food went through some major changes in the past decade. The entry of processed foods, ready to eat varieties, snacks dominated the Indian kitchen. Current situation is such that mostly in the next 10 years homes will be built without kitchens!  Add on to this was the improvements in technology like mobile phones and internet. Our people who were once active slowly started getting more and more tied up in front of computers. As a result the level of physical activity came down. Not to blame anybody but these are some of the “side effects” of modernization finally ending up in OBESITY!

So what happens when we gain weight?

The chances of development of health related problems increase.

To name a few.....

•         Coronary heart disease

•         Type 2 diabetes

•         Cancers (endometrial, breast, and colon)

•         Hypertension (high blood pressure)

•         Dyslipidemia (for example, high total cholesterol or high levels of triglycerides)

•         Stroke

•         Liver and Gallbladder disease

•         Sleep apnea and breathing problems

•         Osteoarthritis (a breakdown of cartilage and bone within a joint)

•         Gynecological problems (abnormal periods, infertility)

•         Depression

The problem of obesity in India starts from very young ages. A very popular Myth in India is that babies must be chubby.. We tend to over feed , elders say that “its baby fat and will go away once the baby grows” but that never happens!

What to do about this obesity??

The options to management of obesity are

1.         Developing healthy eating habits

2.         Increasing physical activity

3.         Pharmocological therapy (Drugs)

4.         BariatricSurgery

The first two options are safe options but effects are only available long term. As humans we all need immediate results so the third option also becomes important. When everything fails we have only one option left - "GO UNDER THE KNIFE" But bariatric surgery has its own side effects and should be avoided whenever possible.

In this review post lets discuss more about the Third option - Drugs for obesity!

The decision to prescribe a weight-loss drug involves a careful assessment of the risks and benefits. As a general rule, an effective regimen should help patients lose at least 2kgs in the first 4 weeks, or 5% of baseline weight in the first 3 months on therapy.

Two classes of weight-loss agents are currently available

Noradrenergic agents for short-term weight loss

Lipase inhibitor for long-term weight loss.

Drugs for short term weight loss :

Phentermine is for short-term (up to 12 weeks) treatment of obesity and is the most widely prescribed weight-loss drug in the United States. Phentermine stimulates the sympathetic nervous system to release norepinephrine, one of the neurotransmitters involved in modulating food intake. Phentermine suppresses appetite and induces satiety because its effects last about 12 hours, phentermine should be taken in the morning. When used in combination with diet and exercise, phentermine has produced an average 3.6 kg greater weight loss than placebo.

Adverse effects include irritability, nervousness, restlessness, dry mouth, insomnia, constipation, and headache, but it has also been associated with hypertension, tachycardia, and palpitations, so it should not be taken by patients with cardiovascular disease or significant hypertension. Blood pressure should be monitored during therapy.

Diethylpropion is similar  to phentermine. Diethylpropion is available in 25-mg standard or 75-mg extended-release formulations, and is approved for short-term treatment of obesity.

Benzphetamine and Phendimetrazine: These drugs also act centrally, releasing dopamine and norepinephrine, resulting in appetite suppression, increased blood pressure, and increased heart rate. As schedule III drugs, however, benzphetamine and phendimetrazine have more potential for addiction, therefore are prescribed less often.

The above mentioned drugs stimulate the central nervous system, and can increase blood pressure and heart rate, while releasing glycerol and free fatty acids.

Drugs for long term weight loss :

Orlistat : It is a gastrointestinal and pancreatic lipase inhibitor.  In the gastrointestinal tract, orlistat binds to gastric and pancreatic lipases, preventing these enzymes from hydrolyzing dietary fat into absorbable free fatty acids. When not absorbed, triglycerides are excreted in the feces, along with cholesterol and fat-soluble vitamins. Taken with meals, orlistat can block the absorption of 30% of ingested fat. In this manner, orlistat reduces caloric intake and may have additional benefits.

Adverse effects of orlistat are fairly common which include steatorrhea, bloating, fecal urgency, fecal incontinence, and oily stools. Orlistat interferes with the absorption of fat-soluble vitamins A, D, E, and K. This class of drug should probably be avoided in patients with gastrointestinal disease or malabsorption syndromes.

Orlistat is currently available as a prescription drug (Xenical® 120 mg/Reeshape 120mg)

There were some unlucky drugs which were withdrawn from the market.

Sibutramine :

Reason for withdrawal - Increased risk for heart attack and stroke.

Sibutramine hydrochloride is a centrally acting drug originally used to treat depression, patients taking sibutramine experienced weight loss as an unexpected effect. Although diminished hunger and increased satiety are the most likely mechanisms of weight loss, sibutramine may also increase thermogenesis, thus increasing energy expenditure by increasing metabolism

Lorcaserin

Reason for concern : lorcaserin-induced valvular heart disease (as well as brain and breast tumors)

Lorcaserin is an anti-obesity drug. The stimulation of specific central serotonin receptors suppresses appetite and induces a feeling of satiety. Users also noticed reduced BMI and waist circumference, lower fasting glucose, lower A1c levels, lower total cholesterol, LDL cholesterol, and triglycerides.

Phentermine/Topiramate:

Reason for concern : cognitive disorders, metabolic acidosis, increased heart rate, and birth defects, suggesting possible teratogenicity.

Qnexa combines low-dose phentermine with a controlled-release form of topiramate, an antiepileptic drug often used for the prevention of migraine headache. Topiramate reduces hunger and promotes weight loss in a dose-dependent fashion, but the peripheral and central nervous system effects (parasthesias, memory impairment, taste disturbance) are significant and intolerable in some patients. Topiramate has the added advantage of having mood-stabilizing properties.

Awaiting !

Naltrexone/Bupropion :

Contrave, another new dual anti-obesity agent, is the combination of the antidepressant bupropion and sustained-release (SR) naltrexone, a drug used to treat alcoholism and other addictions. Bupropion, approved for both depression and smoking cessation, also increases dopamine levels at specific receptors in the brain, which is believed to be responsible for its appetite-reducing effects. These 2 drugs work on the brain reward system and the hunger centers in the hypothalamus, and are believed to be synergistic in reducing food intake.

If approved, this combination therapy could be useful for patients who have issues with food craving. When used with a mild hypocaloric diet and with exercise instruction in overweight or obese patients, it is associated with greater weight loss and greater improvement in several cardiometabolic risk factors compared with placebo.  Combination treatment was generally well tolerated; adverse effects included insomnia, nausea, headache, dry mouth, and a small and transient increase in systolic and diastolic blood pressure.

Still in research:

In the Pipeline

Zonisamide/Bupropion

Antiepileptic zonisamide, an unanticipated effect was weight loss. Zonisamide has sodium and calcium channel blocking activity, as well as dose-dependent biphasic dopaminergic and serotonergic activity. Empatic (made by Orexigen) is a fixed-dose combination of a proprietary formulation of zonisamide SR and bupropion SR.

 Fatigue, drowsiness, sedation, nausea, and cognitive impairments (difficulty concentrating, memory problems, speech and language difficulties) have all been reported with zonisamide use.

Tesofensine

Tesofensine (made by NeuroSearch) is a triple monoamine reuptake inhibitor that blocks the presynaptic uptake of norepinephrine, dopamine, and serotonin. Originally being studied for neurodegenerative conditions such as Parkinson and Alzheimer diseases, unintended weight loss was observed in individuals treated with the drug.

The mechanisms through which tesofensine leads to weight loss are a pronounced effect on appetite suppression and increased energy expenditure. Minor adverse events included elevations in heart rate and significant increases in blood pressure only at the highest tested dose.

Cetilistat

Cetilistat is a new lipase-inhibitor with a similar mode of action to orlistat, inhibiting pancreatic lipase and blocking digestion and absorption of dietary fat. Unpleasant adverse effects, including flatus with discharge and oily spotting, were reported to be less compared to orlistat.  It is probable that, like orlistat, cetilistat will also block the absorption of fat-soluble vitamins.

Pramlintide/Metreleptin

Pramlintide is an analogue of amylin, a hormone secreted by pancreatic beta cells along with insulin. Amylin can increase the absorption of glucose, slow gastric emptying, and by binding to hypothalamic receptors, promote satiety, reduce food intake and elicit weight loss. Metreleptin is recombinant methionine human leptin. Leptin is a neurohormone secreted by adipocytes that also binds to receptors in the hypothalamus to promote satiety. When someone reduces dietary intake to lose weight, leptin levels drop, and this triggers a host of counter-regulatory responses aimed at maintaining body weight. Administration of metreleptin restores leptin concentrations and attenuates the effects of counter-regulation. Pramlintide/metreleptin combination is an injectable therapy, which may limit its application in the general obese population.

Finally!!!

An ideal weight loss medicine is yet to be found. As we all know Metformin for the treatment of type 2 diabetes, causes weight loss by reducing hepatic glucose production and intestinal absorption from the gastrointestinal tract, and enhancing insulin sensitivity. Liraglutide (Victoza®), another drug that is already approved for the treatment of type 2 diabetes, induces moderate weight loss of approximately 2-3 kg. The glucagon-like peptide-1 (GLP-1) receptor agonists exenatide and liraglutide are newer medications for diabetes that have favorable effects not only on glycemic control but also on weight loss. These drugs do not qualify as weight loss medicines but are useful in patients with combined problem of weight gain and diabetes



LOSE WEIGHT

P.S - Not many drugs are available in India, Content of this blog post has been collected from authenticated sources.(www.medscape.com)