Category Archives: Weight loss

Insane Medicine – Liraglutide (Saxenda) for weight loss!!

  • Liraglutide is a glucagon-like 1 peptide that has been available for diabetes management for a few years and now has an added FDA approval for weight loss management!!
  • There are more options for weight management as of now!
    There are more options for weight management as of now!


  • To date, Phentermine/topiramate ER (Qsymia) is the most effective drug available. Locaserin (Belviq) is another approved drug for weight loss, but it is less effective.  However, it is better tolerated. Other options such as Xenical are helpful, but it prevents absorption of food and can cause excessive bloating and gas in some patients. Contrave (Wellbutrin and Naltrexone) is also effective but has neuropsychiatric effects.
  • Liraglutide is used to treat type 2 diabetes at a dose of 1.8 mg a day. It is injectable. The weight loss form of the drug is a dose of up to 3.0 mg a day injected. The amount of weight loss varies as the dose approaches the upper limit of 3 mg a day.
  • Liraglutide decreases appetite and therefore energy intake, which is how it causes weight loss. It also delays gastric emptying. Used as an adjunct to physical exercise and dieting, it has resulted in up to an 8 kg body weight loss over the 56 week course of treatment [ −8.0±6.7% (−8.4±7.3 kg)].
  • Liraglutide treatment was associated with reductions in cardiometabolic risk factors, including waist circumference, blood pressure, and inflammatory markers. Fasting lipid profiles were also improved as well. The combination of weight loss and improved glycemic control probably contributed to the observed reductions in the prevalence of prediabetes and the delayed onset of type 2 diabetes.
  • Side effects include an increased incidence of gallstones, which commonly increase with weight loss.  Nausea and constipation (or diarrhea) has been reported. Rarely, pancreatitis and kidney failure has occurred. The FDA has required a boxed warning about the risk of thyroid C-cell tumors in the package insert, and in patient’s with a family history of Multiple Endocrine Neoplasia Type 2 or medullary thyroid carcinoma, this treatment is to be avoided.
  • Treatment is started at 0.6 mg injected a day and increased weekly by another 0.6 mg until a total of 3 mg a day is injected. At 16 weeks, if a 4% body weight loss is not achieved, therapy should be stopped. Total cost per month is about $1000.00!
  • For patients who have a BMI>30 (Body mass index) and are not diabetic, or have a BMI>27 with a risk factor, such as hyperlipidemia or diabetes, Saxenda is a consideration for weight loss.
  • Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to methylglyoxal stress

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Liraglutide (Saxenda) for Weight Loss

Insane Medicine – Cardiac Rehabilitation will save your life

Cardiac rehab and healthy eating save lives
Cardiac rehab and healthy eating save lives!

eat healthy

  • Have you had a heart attack? Then why aren’t you in cardiac rehab if your doctor says it’s okay?
  • Those who are involved in cardiac rehab have a 47 % decrease in heart attack risk over the next two years! Also, those who participate have fewer hospital admissions and live longer.
  • Cardiac rehab is an option post-heart attack, as well as for those with arrhythmias and heart failure. It is associated with decreased mortality and prolonged survival.
  • Cardiac Rehab is coached by trained professionals who teach you how to appropriately exercise based on your capabilities and prescription. This improves your functional status.
  • It also involves nutritional counseling, teaching the patient to eat a low fat and sodium diet to help manage cholesterol levels and blood pressure. This allows you to maintain a healthy weight.
  • cardiac rehab also helps you maintain a regimen. More important, one must take their prescribed medications for optimal outcomes. Compliance leads to success. Education about medications that are important is a key  factor.
  • Cardiac rehab also educates one to avoid unhealthy habits, such as smoking and maintaining diet. likewise, the mental aspect of a post-cardiac condition is crucial in maximizing outcomes. Depression and other mental disorders must be fully addressed and treated.
  • Exercise creates stronger muscles and improved cardiovascular fitness that improves ones emotional state as well. Cardiac rehab must be continued in the home environment for maximal impact.
  • The journal BMJ showed that even a little bit of exercise provides noticeable benefits of health. the goal is 150 minutes of exercise per week, but even small amounts of physical activity may decrease the mortality risk.
  • Exercise helps with depression and boosts your natural endorphins that make you feel better, resulting in increased energy levels. Exercise allows you to take control of your life and is a mood enhancer that gives you an overall sense of well-being.
  • Depression and anxiety can be blunted by such exercise programs, especially when they are maintained at home as well. Meditation and behavior modification are key components to creating a healthy lifestyle. People who are depressed and feel hopeless have a higher rate of dying from their cardiac disease. exercise at least 30 minutes a day, working your way up to that amount even if you don’t have the internal motivation to do so.

Insane Medicine – New future treatment for obesity –

Insane Medicine: incretins and dpp
Incretins and DPP . GLP-1 stimulates the release of insulin to help lower blood sugar after a meal. It also prevents glucagon release. Glucagon causes the breakdown of glycogen stores in the liver into glucose, thereby raising blood sugar. DPP-4 is an enzyme that inactivates GLP-1.
Action of GLP
Action of GLP – as before, GLp is produced in the stomach in response to food and causes the pancreas to increase insulin production and decreases glucagon expression.
gip and glp actions
Gip and glp actions

Our generally bad diets, high in fat and processed sugar result in obesity and metabolic derangements. As a result of years of insulting foods, the body’s cells reprogram themselves in such a way that even if one exercises and diets well, it remains difficult to lose weight.

Bariatric surgery has been effective in producing significant weight loss and metabolic changes, allowing one to have less appetite, burn more calories, lose fat, and lose weight.

In the diagram above, the body normally responds to a meal by producing GLP-1 and GIP, which act on the pancreas to produce more insulin to lower the blood sugar. GLP-1 also prevents the secretion of glucagon, which is a hormone that causes the production of glucose from fat. In type 2 diabetes, the body does not respond to GLP-1, GIP, or glucagon as it should, so the GLP-1 no longer suppresses appetite or promotes insulin production after a meal. The failure of glucagon to be active in the body results in fat accumulation.  Bariatric surgery has been the only method to boost the effective functioning of GLP-1, GIP, and glucagon.

Researches at the Helmholtz Diabetes Center in Munich, Germany have produces a protein that takes structural pieces of GLP-1, GIP, and glucagon and merges them into a single functional unit.  This drug, when injected into rats, increased glucose lowering, fat burning, and weight loss in obese rats through clear metabolic changes. This resulted in test rats to lose up to a third of their body weight! A pill and no surgery…sounds like a great opportunity!

Insane Medicine – Top causes of death in the US

The National Vital Statistics System published mortality data recently, showing the life expectancy of a baby born today is 78.8 years! For women, it is 81. 2 years and for men, it is 76.4 years.

The causes of death listed are, in order of highest frequency:

  1. Heart disease
  2. Cancer
  3. Respiratory Diseases
  4. Stroke
  5. Non-intentional injury
  6. Alzheimers
  7. Diabetes Mellitus
  8. Influenza/Pneumonia
  9. Suicide.


The report is found at this link:


There are many modifiable causes of death and morbidity listed above. For example, by losing weight, eating healthy, controlling blood pressure and diabetes by diet, exercise and medication, one can offset the risks posed by heart disease, cancer, stroke, and diabetes. The influenza vaccination and pneumovax can decrease the mortality of influenza and pneumonia.  Work place safety, seat belts, and other  safety measures can help alleviate accidental deaths.  Lastly, quit smoking – that will decrease cancer risk and lung failure risk.

Insane medicine: Pregnant mothers may need to watch their fat intake during pregnancy – it may affect their children!

Insane medicine - Fat mice get fat by eating fat diets. The effect damages their progeny.
Insane medicine – Fat mice get fat by eating fat diets. The effect damages their progeny.
  • The average American diet has 37% fat content. The recommended amount is 25-35% according to the 2010 dietary guidelines. Four studies have shown the bad impact that high fat consumption during pregnancy has on the fetus.
  • Mice fed 45 % fat diets during pregnancy demonstrated deficits in memory with higher anxiety and depression scores as well! What’s worse is there was epigenetic effect as well – the following generation of mice displayed memory loss and behavioral change as well. Here is the link:
  • A study in rats also showed that the mother’s diet, if high in saturated fat and branched chain amino acids(BCAA), would prime the microglia of their offspring. Microglia are the mmune cells of the brain and will secrete pro-inflammatory cytokines in the hippocampus (a learning center). Also high levels of BCAA compete with tryptophan transport across the blood brain barrier. When there is less tryptophan in the brain, the brain makes less serotonin which then results in anxiety! The pups were found to have depression and anxiety scores that were much higher than pups born to mothers who ate a more fat-restricted diet. Here is the link:
  • Other studies demonstrated that a high fat diet in the pregnant mother causes the down-regulation of oxytocin systems in the brain of offspring and causes anxiety to be prevalant in the progeny. This effect does not occur in the pups of normal fed pregnant female rats. In this study it was found that the fewer numbers of oxytocin-positive neurons within the PVN (paraventricular nucleus), the more anxious the rats were as adults. Oxytocin projections to the brainstem acts as an appetite suppressant,  hence leading to overeating in the progeny of overfed pregnant females. Oxytocin also plays a role in maternal behaviors as well. Mother rats literally groom their daughters to be attentive or neglectful mothers themselves and this is associated with the presence of normal numbers of oxytocin projections. If a rat has fewer oxytocin projections, they will be neglectful parents more likely. Hence multiple pathways of brain function  may be affected in the young of a high-fat diet mother. Here is a link:
  • These effects also occur in primate studies as well – monkeys whose mothers are fed high fat diets have fewer dopamine projections to the nucleus accumbens ‘reward center’ of the brain. As a result, they have a reward deficiency when they eat food and don’t get satiated at a normal level of food. Rather, they  must take in more food to get the same amount of reward as another monkey that came from a normal-fed mother and had normal dopamine projections in the brain. Thus they get fatter.
  • Dietary guidelines recommend a diet of 25-27% fat. See this link for the recommendations of a standard diet:  However, the average person takes in 37% fat or more!! See this link showing how much we really take in:
  • We eat more than we think. We need to recognize that our food choices and stress patterns can affect our children through epigenetic mechanisms especially. We can set up our children for failure. These studies are done in standard models for humans and show the impact high fat diets in pregnancy  have on their children: Memory deficits, anxiety, depression, and future weight problems may echo the studies in rat and monkey populations.  The apple doesn’t fall far from the tree, for it seems that overweight parents have overweight children. Food for thought!!

Insane Medicine – Topiramate and Phentermine and weight loss.

Insane medicine - Topamax (Topiramate) and weight loss
Insane medicine – Topamax (Topiramate) and weight loss.
  • Qsymia is a new combination of older medications Phentermine ( of the fen-fen fame) and Topiramate. The question that some people have is why not just use one or the other or combine individual pills of phentermine and topiramate?
  • What is Qsymia ? Qsymia is a fixed combination of phentermine and topiramate Extended Release in the following combinations: 7.5/46 and 15/92 mg.
  • Topiramate is approved for Migraine prophylaxis and epilepsy and was found to induce weight loss in people using the drug. The topiramate use resulted in body mass index lowering, mean weight loss, decreased systolic blood pressure, and a decreased hemoglobin A1C, which meas less insulin resistance and better control of diabetes.  Topiramate improves insulin sensitivity is a result of potassium-ATP channel activation in the brain with similar effect peripherally. This is the link: 
  • Topiramate also has effects on the liver’s sensitivity to insulin as well through a modulation of liver receptors which caused fat loss, better glucose control, and better cholesterol control. Here is the link:
  • Topiramate induced weight loss in type 2 diabetics and improved glucose control as shown through a lower hemoglobin A1C ( a measure of blood glucose control over time). Here is the link: 
  • Topiramate studied at doses of 96 mg/day and 192 mg/day in Type 2 diabetics demonstrated a 6-9% weight loss  as dose escalated, improved glucose control through a lower hemoglobin A1C, and lower systolic blood pressure and urinary albumin levels.  Here is the study link:
  • In these studies, dietary modification and exercise was included with Topiramate to help the weight loss.
  • Using Topiramate  as a monotherapy for obesity was abandoned due to dose-dependent neuropsychiatric and cognitive adverse events, such as memory and concentration impairment, language difficulties and mood changes. Other side effects include paresthesias (tingling feeling) and taste changes. It is teratogenic in pregnancy, so women must be on birth control and not be pregnant is using this. Also, topiramate can decrease the efficacy of birth control pills.
  • The exact mechanism of action for weight loss with topiramate is not known, but animal experiments suggest that topiramate-induced weight loss results from increased energy expenditure, decreased energetic efficiency and decreased caloric intake as an appetite suppressant.
  • Phentermine is a noradrenergic drug that stimulates noradrenaline release and reduces food intake by acting on β-adrenergic receptors in the perifornical hypothalamus. It’s sympathomimetic actions are similar to amphetamine. It was approved for the short-term treatment of obesity by the FDA in 1959. However, strong evidence to demonstrate its long-term safety and efficacy is still lacking.  It does produce significant weight loss, lipid reductions, and waist size decrements. Major side effects are dry mouth and insomnia.
  • The phentermine/topiramate combination is a once-daily formulation designed to provide an immediate release of phentermine and a delayed release of topiramate that would not be achieved by simply combining the two drugs already marketed (i.e. the drug combination produces peak exposure to phentermine in the morning and a peak concentration of topiramate in the evening). It’s efficacy was shown in two trials, the EQUIP trial and the CONQUER trial, which significant weight loss relative to placebo of 8-10 % over a year.
  • Adverse events associated with phentermine/topiramate treatment were generally consistent with those reported for phentermine (i.e. dry mouth, constipation, insomnia and palpitations) and for topiramate (i.e. dizziness, paraesthesia, disturbances in attention, metabolic acidosis and renal calculi), together with headache, dysgeusia (distortion of sense of taste), alopecia and hypokalemia. Other potentially serious safety concerns regarding phentermine/topiramate include teratogenicity, elevations in resting heart rate and anxiety/depression.
  • The FDA link for Qsymia and it’s approval studies is as follows:
  • Although the combination of drugs causes a slight heart rate increase, it does lower blood pressure and there have not been any increase in cardiac events.  Cognitive dysfunction, with difficulty with language, memory, confusion or word-finding ability is a concern due to the topiramate in this combination product as well, but has less impact due to the extended-release aspect of the packaging.

    Insane Medicine - Qsymia for weight loss
    Qsymia for weight loss
  • Overview of anti-obesity drugs:
  • Pharmacotherapy for obesity:

Insane Medicine – Obesity increases your risk of Alzheimer’s disease.

  • Obesity increases your risk of diabetes, hypertension, stroke, and cancer. It also increases your risk of cognitive decline. It has been shown, however, that weight loss can reverse some of the cognitive decline! This was shown in patients with gastric bypass who were found to have improvements in their executive functioning after surgery and weight loss. Executive functioning includes the processes of organizing, planning, an decision-making. Also improved is attention and memory.
  • Also linked to this cognitive decline in obese people is lack of physical activity, poor inflammatory-type diet, and depression.
  • Increased fat causes problems in executive functioning, decreased memory, and  decreased processing speeds, all of which worsen with age as well. The high content of simple sugars and saturated fat cause a disruption in the blood-brain barrier that allow inflammation to occur in the brain, especially from the passage of Interleukin-1, which is secreted by fat and passes through this disrupted brain barrier. The hippocampus is the target that is affected, thereby diminishing memory by disrupting the connections in the brain called synapses. In the lab, lowering the brain’s level of interleukin-1 results in improved cognitive performance.

What to do? Emphasis on healthy choices and then weight loss:

  • Exercise regularly
  • Decrease stress through relaxation, meditation, or other routes.
  • Get plenty of sleep
  • From Harvard's healthy eating plate - one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken - all unprocessed.
    From Harvard’s healthy eating plate – one-half the plate is for fruits and vegetables, one-fourth with whole grains, the rest is devoted to fish, beans, nuts, or chicken – all unprocessed.


  • Eat a proper diet, less processed food, for example, use whole wheat bread and avoid processed meats such as hot dogs or salami. Choose low fat dairy products. Avoid additives or flavorings.Chose healthy plant oils such as canola and olive oils. Eat smaller portions of food.
  • Caffeine intake can  be safe in adults up to 400 mg a day and can increase wakefulness, better recall of spatial information, improved attention, faster reaction time,  and decrease feelings of fatigue.  It may also enhance memory and cognition as well. One study linked drinking three to five cups of coffee a day with a 65 % decrease in dementia. Caffeine was noted to decrease the formation of tau protein in the hippocampus of rats. Tau protein deposition is a hallmark of Alzheimer’s disease.  Caffeine enhances the brains’s memory and allows the consolidation of information for the long term.

Insane Medicine – Brown fat may be the anti-fat! Exercise is the key to activate it and lose weight!

Insane Medicine - Brown fat may be involved in glucose and fat metabolism
Brown fat appears to be involved in glucose and triglyceride regulation as well as insulin sensitivity. It’s absence or failure in some people may lead to obesity.

brown fat

  • Our body has three types of adipose (fat) cells: white, brown, and Brite fat. White fat is what we classically refer to as fat.  It has become apparent that fat is not just a storage agent of triglycerides (fat), but that it’s behavior can affect the process of metabolic syndrome in obesity, in which a person has cholesterol/triglycerides issues, and insulin insensitivity. This leads to high cholesterol and diabetes.The paper links below list some theoretical information about how brown fat activation may be a key to weight loss.

  • Brown fat (BAT) has been found in humans but seems to disappear by the age of two. It is involved in heat generation (without shivering being the cause of this heat production) Brown fat is stimulated by cold exposure and decreases with age and with weight increases. The higher your BMI (body mass index) the less brown fat you have. Brown fat has a role in glucose disposal and triglyceride clearance by sucking it from the blood stream and generating heat. It generates the heat by ‘uncoupling oxidative phosphorylation” in which the mitochondria (powerhouses of the cell) don’t produce ATP (energy units) as they usually do with their proton energy gradients, but rather generate heat.
  • BAT is activated by cold and causes the cells to take up more glucose to produce heat. Insulin also causes the brown fat to take up glucose. It has been found that capsinoles (found in chili peppers) stimulates thermogenesis in brown fat.
  • Decreased activity of BAT results in metabolic syndrome in which there are glucose homeostasis problems, lack of insulin sensitivity, and poor triglyceride clearance, leading to diabetes and high cholesterol. Again BAT decreases with age but increases with cold exposure and adrenergic stimulus (adrenaline). Brown fat locally produces leptin and interleukin 6 as local hormones and has a substance UCP-1 on it’s surface (white fat does not have this)
  • White fat is the common fat you recognize and acts as a storage tank for triglycerides, producing leptin, adiponectin, and adipokines locally. It does not have UCP-1 on it. It comes from a different origin than brown fat.  Brown fat appears to originate from a myogenic (muscle) precursor!
  • Brite fat is the third type of fat, similar to brown fat in many ways and can convert to brown fat. This process is referred to as browning. This occurs by contact with Irisin, a hormone myokine made in the muscle in response to activity/exercise.  Irisin recruits Brite adipocytes to become brown adipocytes.
  • Brown fat makes up 5% of the basal metabolic rate and may potentially be involved with up to 15% of the daily energy expenditures!

The summary is that brown fat, if it can be turned on, may be a way to decrease weight and reverse glucose intolerance  (diabetes) and cholesterol problems in obese people, who have less brown fat than their thin peers. Current options are: Exercise to turn on the brown fat and increase your intake of capsinoles (chili peppers) which may stimulate thermogenesis. Cold exposure also turns on brown fat, but that is probably unsafe as an option, nor pleasant! Science is working on other solutions as well.

Insane Medicine – Environmental Obesity

Insane Medicine -Some obesitty-causing factors may be environmental in origin
Insane Medicine -Some obesitty-causing factors may be environmental in origin.
  • There are many additional environmental ingredients added to our food that potentially have a bad impact on our health. These additives are used to enhance food flavors or extend their shelf-life. There may be some connection to the increased rates of obesity and these additives.
  • Certainly increased food intake, decrease activity, and increased processed foods have added to the obesity epidemic, there is some indication that environmental chemicals may be a component.
  • Phthalates: Used in food production during processing and production can increase fat storage in humans.
  • Organotins in seafood and shellfish modify fat storage and energy metabolism.
  • Heavy Metals in rice, spinach, lettuce, and some herbs causes endocrine disruption and other metabolic issues.
  • Bisphenol A in polycarbonate bottles and canned food disrupts the endocrine system.
  • Persistent organic pollution in oils, seafood, berries, animal products disrupts sugar and fat metabolism.

BPA is released more from containers when they are heated or an acidic food is placed in them, whereas persistent organic pollutants enter the food chain as animals and plants accumulate the toxic materials ans pass it to others. The bottom line is a disruption of endocrine regulation.

How to avoid the toxins: Never heat items in a plastic container and do not place plastic containers in the dishwasher. Plastic items with the codes 3 (Phthalates), 6 and 7 ( contains BOA) should be avoided. It is best to make your food from scratch to avoid processed foods that may have these items in them as flavorings or to enhance shelf life.

Insane Medicine – Contrave, a new medication for weight loss

  • Just approved is a combination pill of Naltrexone ( an opioid-receptor antagonist) and buproprion (used for depression and smoking cessation) for weight loss. the medication name is Contrave.
  • This is to be used for people with a BMI> 30 kg/meter-squared, in addition to diet and exercise to promote weight loss.
  • Other medications used for weight loss have had issues with continued effectiveness, such as Lorcaserin (Belviq) and phentermine/topiramate (Qsymia) which lose efficacy after the initial year of use. Orlistat is somewhat effective over a four year period of use, but it has a lot of side effects.
  • Liraglutide, a diabetic medication known as a GLP-1 receptor antagonist, is being evaluated for weight loss by the FDA currently.
  • The way that buproprion works to lose weight is by stimulating neurons in the hypothalamus that  regulate appetite. These neurons then secrete beta-endorphin, that otherwise would stimulate appetite. That is why Naltrexone is added to buproprion, so as to block the beta-endorphin effect.
  • The effectiveness of Contrave over a year showed more than a 5% body weight loss with improvements in waist circumference, lower LDL-C levels, higher HDL levels, improved insulin resistance, lower triglycerides, and a reduction of hemoglobin A1C. In other words, people lost weight, improved their diabetic control and their lipid profile over the first year.
  • There are potential drug interactions with Contrave. Side effects include nausea, constipation, and rarely, seizures. Due to the Naltrexone in the medication, patients on chronic pain medications cannot use Contrave, as it will reverse opioid effectiveness. A black box warning on the medication also includes the potential for neuropsychiatric abnormalities.
  • If after three months of use, a person has not lost 5% of their total body weight, the medication should be stopped. Dosing is a tablet in the morning and at night (Naltrexone 32 mg/Buproprion 320 MG – per tablet).
  • Qualifications for use: BMI>30 with obesity related medical issue such as hypertension, diabetes,  or high cholesterol.