Diabetes Drugs - Number 6 on the Top 10 Most Dangerous Drugs List
Diabetes medications (Actos, Avandia, Byetta, Januvia, Janumet, Bydureon, Victoza, and others) are no substitute for a diabetes education and treatment program that includes diet, exercise and the right supplements like chromium or foods that contain nutrients vital to pancreatic function - especially when the risk of these drugs is examined. Medications are just a Band-Aid compared to a healthy diet and carb control, exercise and weight loss, but it’s often easier to take a medication than make changes or to prescribe a pill than to insist on lifestyle changes. And, it’s as much patient responsibility as physician.
Having said that, it’s not always easy to eat right or lose weight but relying on a medication can be downright dangerous.
Diabetes is the leading cause of blindness, kidney failure, amputations and the seventh leading cause of death. When your body does not produce enough insulin or is resistant to insulin (metabolic resistance), sugars can’t move into your cells, in order to be utilized for energy. ATP production is altered, and the brain is the first organ to suffer.
Yet, the costly drugs used to treat diabetes are potentially more dangerous that the disease itself. Relatively new diabetes drugs such as Avandia, Actos, Byetta, Januvia, and others not only have dangerous side effects, many are the hotbed of wrongful death lawsuits. And despite lawsuits and huge settlements most are still on the market. The problem is multidimensional – there is a lack of long term studies although some side effects do not take years to adversely affect patients. Drug companies often skew results to make studies look more promising or even pay other companies to juggle the numbers. Once on the market the FDA is less likely to remove a drug, even if intentional errors in data or studies are exposed, and even if it is an out and out lie just as omitting information on serious side effects. Instead the company pays a fine which is just a slap on the wrist to companies whose profits are in the multi-billions. The biggest problem lies in the ethics of the companies who are doing the studies because new drugs mean big money. The process of moving into the marketplace is costly, but once to market highly profitable. According to Mark Salzman, Professor of Biomedical Engineering, Chemical & Environmental Engineering & Physiology at Yale University, the average cost of taking a drug to market is about $1.2 Billion. Diabetes drugs are extremely lucrative for drug companies and shareholders despite the costs of going to market. In 2014, Merck & Co generated about six billion U.S. dollars in anti-diabetic revenue for and is expected to generate over eight billion U.S. dollars yearly by 2020 which may be a conservative figure. Diabetes drugs are a $63 Million dollar a year business. 
As we all know you have to spend money to make money but what are the costs in human lives?
Mechanism of Action and Potential side effects of common diabetes drugs:
1. (Metformin - Glucophage, Glumetza, others): Metformin is one of the most widely used Type 2 diabetes medications in the world. Since it was discovered in 1929, its side effects are very well known. As a consequence, many doctors are comfortable prescribing it as a frontline medication or in combination with other medications. In fact, most combination oral medications contain metformin. The primary mechanism metformin uses to reduce glucose levels in the blood is to suppress glucose production by the liver. With insulin resistance, the liver will continue to produce glucose even when there are elevated levels of insulin. Metformin also has a lesser effect on sensitizing fat and muscle cells to insulin. Studies also indicate Metformin may protect against ovarian cancer as well as breast, lung, pancreatic, and hepatocellular cancer. But that possibility is not reason enough to prescribe the drug.  In fact, upon closer examination of warnings to health care professionals, it becomes clear that Metformin manufacturers provide physicians with a warning that also acts as a disclaimer. In order to prevent legal concerns from arising, the fine print on Metformin states that the drug should not be prescribed to those with existing circulatory, excretory, as well as endocrine ailments. Since diabetes goes hand in hand with those health issues, it would make sense that most people should not be prescribed the drug. Nevertheless, physicians seem to frequently overlook such a fact, hence leading to irreversible repercussions. Rightfully so, physicians who disregard such a warning often end up being sued as patients often die from lactic acidosis, and at times renal failure, instead of being relieved from the limiting effects of diabetes.
Side effects: Abdominal or stomach discomfort, cough or hoarseness, decreased appetite, diarrhea, fast or shallow breathing, fever or chills, general feeling of discomfort, lower back or side pain, muscle pain or cramping, painful or difficult urination, sleepiness, anxiety, blurred vision, chest discomfort, cold sweats, coma, confusion; cool, pale skin, depression, difficult or labored breathing, dizziness; fast, irregular, pounding, or racing heartbeat or pulse, feeling of warmth, headache, increased hunger, increased sweating, nausea, nervousness, nightmares, redness of the face, neck, arms, and occasionally, upper chest; seizures, shakiness, shortness of breath, slurred speech, tightness in the chest, unusual tiredness or weakness, wheezing, behavior change similar to being drunk, difficulty with concentrating, drowsiness, lack or loss of strength, restless sleep, unusual sleepiness, sickness with alcohol, low B12 levels, kidney complications, decreased liver function and hepatitis, metallic taste, lactic acidosis which can be life threatening.
2. Sulfonylureas and non-sulfonylurea secretagogues (Glucatrol, Diabeta): There are several well-known Type 2 diabetes drugs that use sulfonylureas as their base. Those include glipizide (Glucotrol), glyburide (Diabeta) and several others. These work to decrease blood glucose levels by stimulating insulin release by the beta cells in the pancreas. Pancreatic beta cells are the cells primarily responsible for releasing insulin.
Side effects: note there are a large number of these drugs and each may have additional side effects. Always read side effects information that your doctor and pharmacist should provide: easy bruising or bleeding (nosebleeds, bleeding gums), feeling tired or short of breath, rapid heart rate; nausea, diarrhea, upper stomach pain, constipation, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); pale skin, fever, confusion; or throbbing headache, severe nausea and vomiting, fast or pounding heartbeats, sweating or thirst, feeling like you might pass out; skin rash, redness, or itching, low blood sugar, upset stomach, weight gain
3. Alpha-glucosidase inhibitors and amylin analogues (Pramlitide): These drugs slow the digestion of sugar. These are the least effective medications for lowering blood sugar and are rarely used in the United States. Amylin analogues also have a modest effect on blood sugar, and are injected with a dosing pen. The only product available is called pramlintide.
Side effects: Anxiety, blurred vision, chills. cold sweats, coma, confusion, cool pale skin, cough, depression, difficulty with swallowing, dizziness, fast heartbeat, headache, hives, itching, or skin rash; increased hunger, nausea, nightmares, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, seizures, shakiness, slurred speech, tightness in the chest, unusual tiredness or weakness, gas, bloating and diarrhea. You should not use these drugs if you have an inflammatory bowel disease, ulcerative colitis, Crohn's disease; a chronic intestinal disorder that affects your digestion; blockage in your intestines; or a stomach disorder that causes excess gas, has been known to cause pancreatitis.
4. Thiazolidinediones: Rosiglitazone (Avandia) and pioglitazone (Actos): Primarily, pioglitazone decreases blood glucose levels by making muscle and fat cells, and, to a lesser extent, liver cells, more sensitive to insulin. Actos has been on the market since 1999 and has been one of the most popular drugs in the United States for treating Type 2 diabetes since 2007. 
Side effects: Chest pain, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, irregular heartbeat, problems with teeth, shortness of breast, swelling of the face, fingers, feet, or lower legs, tightness in the chest, trouble with breathing, wheezing, weight gain, unusual bleeding or bruising, loss of appetite, nausea or vomiting, stomach pain, yellow eyes or skin, liver failure, anemia, weight gain, increased risk of congestive heart failure and bladder cancer.
Several thousand Actos lawsuits have been filed, alleging that its manufacturer, Takeda Pharmaceuticals, misled doctors and patients about the side effect risks associated with the drug. 
Avandia (rosiglitazone): This drug comes from the same controversial class of drugs, glitazones, as Actos, and works in a similar way. It has been found to severely increase the risk of heart failure. So much so that, although not banned in the United States, it can only be prescribed by a small group of doctors.
5. Meglitinides (repaglinide (Prandin) and nateglinide (Starlix): Meglinitides work like sulfonylureas by stimulating the pancreas to release insulin in response to a meal. It closes ATP-dependent potassium channels in functioning pancreatic beta cells. This blockade of potassium channels depolarizes the beta cells, which leads to opening of calcium channels resulting in influx of calcium. Increased intracellular calcium induces insulin secretion.
Side effects: diarrhea, weight gain, low blood sugar, severe abdominal pain that may radiate to back, rapid heart rate, jaundice, liver failure, fever, confusion, weakness, stuffy nose, sneezing, sore throat, swelling in face and tongue, burning eyes, rash that may peel or blister, joint pain, seizures
6. Dipeptidyl peptidase-4 inhibitors (DPP-4) sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta): These drugs keep the hormone incretin from being broken down, stimulating insulin production and slowing digestion.
Side effects: respiratory and urinary tract infections (UTI), pancreatitis, high blood pressure, anemia, disabling joint pain, depression, headache, fatigue and many others. 
Some doctors are concerned by reports of a possible increased risk of pancreatitis (inflammation of the pancreas) and pancreatic and thyroid cancer associated with incretin-based therapies like Onglyza. Hundreds who took these drugs filed lawsuits against the drugs’ makers after they developed pancreatitis or pancreatic cancer, claiming that the drug companies failed to warn of the risk. 
According to the New England Journal of Medicine , the American Heart Association , and identified by the FDA in February 2014, another potentially fatal side effect of Onglyza is heart failure.  This increase in risk was noted to be highest among patients with elevated levels of natriuretic peptides, prior heart failure, or chronic kidney disease.
7. GLP-1 receptor agonists (Exenatide (Byetta) and liraglutide (Victoza): These medications slow digestion and help lower blood sugar levels, though not as much as sulfonylureas. This class of medications isn't recommended for use alone.
Side effects: include nausea and an increased risk of pancreatitis.
8. SGLT2 inhibitors (canagliflozin (Invokana) and dapagliflozin (Farxiga): These are the newest diabetes drugs on the market. They work by preventing the kidneys from reabsorbing sugar in the blood. Instead, the sugar is excreted in the urine. Forxiga, marketed by AstraZeneca inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. The drug was approved in January 2014 and has already had bad press and has been called the worst new drug of 2014. 
The FDA requires a warning for bladder cancer patients that they shouldn’t take Farxiga because it might make their cancer worse. In addiction they are requiring the company to study 17,000 diabetes patients for at least four years to determine whether and how often patients taking Farxiga are diagnosed with cancer, liver problems, or heart disease when the drug is taken for a longer period of time.
Side effects: include hair loss, dehydration which can lead to kidney failure, mild to moderate kidney damage, genital fungal and urinary infection, general infections, influenza, increased ketoacidosis, hepatitis, liver failure, back pain, bone fractures, breast and bladder cancer and heart failure. 
Lawsuits Against Drug Manufacturers:
When one begins to look at the sheer numbers of drugs available to treat diabetes it can be mind-boggling and keeping the lawsuits straight even more so. Drugs in the incretin mimetic class which work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal include:
• exenatide (Byetta, Bydureon) Bristol-Myers Squibb & AstraZeneca
• liraglutide (Victoza) from Novo Nordisk Pharmaceuticals
• saxagliptin (Onglyza, Kombiglyze XR) Bristol-Myers Squibb
• alogliptin (Nesina, Kazano, Oseni) Takeda Pharmaceuticals
• linagliptin (Tradjenta, Jentadueto) Eli Lilly & Boehringer Ingelheim
• sitagliptin (Januvia, Janumet, Janumet XR, Juvisync) made by Merck
The U.S. Food and Drug Administration approved Byetta, Januvia, Janumet and Victoza in 2005, 2006, 2007 and 2010, respectively. These drugs are classified as incretin mimetics. Since approving them, the FDA has issued warnings linking the drugs to serious complications such as pancreatic diseases, yet these products remain on the market, putting patients at risk.
Lawsuits against all of the manufacturers allege that the drugmakers marketed these medications despite knowing that they were dangerous and failed to warn the public about the risk of pancreatic cancer and pancreatitis.
Questions about diabetic drug risks regarding pancreatitis, a painful and possibly lethal inflammation of the pancreas, arose soon after Byetta, now sold by Bristol-Myers Squibb and AstraZeneca, was approved in 2005. The drugs’ labels already contain warnings about that. What is new and potentially more serious is a possible risk of pancreatic cancer, which is virtually untreatable and kills most victims within a year.
As early as 2007, incretin mimetic manufacturers were aware that these drugs could cause cancerous cells to form in the pancreas. In that year, the FDA alerted the public that Byetta caused acute pancreatitis in patients and the drug’s label was updated to reflect this injury. This safety alert failed to mention the risk of pre-cancerous and cancerous cells forming from the drug.
Pancreatic cancer is not only the fourth-leading cause of cancer death in the United States, but is also one of the few cancers for which survival statistics has not improved in decades. The seriousness of this disease is further aggravated by how the drug companies negligently tested and labeled the medications, merely to increase profits.
Acute pancreatitis can accelerate cancer cell progression in the pancreas. Unfortunately, diabetes itself is also a risk factor for pancreatic cancer; therefore these drugs significantly increase the risk of cancer growth in patients already predisposed to the disease. About six years later, in 2013, the FDA finally issued a notice on reports of pre-cancerous tissue in incretin mimetic patients after startling information surfaced regarding certain diabetic drugs and cancer. 
Dr. Peter Butler, a researcher at the University of California, Los Angeles (UCLA), and specialist in endocrinology, diabetes and metabolism initially turned down a request by Merck to do a study on their medication Januvia. He later relented. What he found was disturbing and led him on a crusade to study the potential carcinogenic effects of the drugs. When he released details of the UCLA Diabetes Study it forced the Food and Drug Administration (FDA) to take a hard look at certain diabetic drugs. The findings of Dr. Butler’s study suggest that there may be a significantly higher risk of pancreatic cancer, pancreatitis, and thyroid cancer when using some diabetic drugs. His work and findings were not only a wake-up call but have probably saved lives. 
Actos has also been in the center of wrongful death lawsuits. Finally the FDA issued a warning that it is associated with increased risk of heart disease as well as bladder cancer.
Surprisingly, the potential link between Actos and bladder cancer was actually acknowledged before Actos was introduced to the market in 1999. Actos’ manufacturer, Takeda Pharmaceuticals, had done the required clinical trials for Actos which actually discovered a high rate of bladder tumors among male rats.
Rather than stopping the production of Actos, the Food and Drug Administration (FDA) allowed Takeda to proceed in selling Actos. Several years after the acceptance of Actos the first human studies of Actos bladder cancer began. In 2007, Takeda acknowledged that there were fairly substantial data suggesting that there may be a link between Actos and bladder cancer.
Despite this knowledge the drug remains on the market. WHY? Actos, generates over $4 billion in sales annually.
FDA Issues New Invokana Warning
On Sept. 10, 2015, the Food and Drug Administration issued new warnings about Invokana side effects:
Canagliflozin — the active ingredient in Invokana and Ivokamet which are also in the same class of incretin mimetic drugs — may increase risk of bone fractures and decrease bone mineral density and these fractures can occur as early as 12 weeks. 
The FDA added new warning and revises “Adverse Reactions” section of the product label for Invokana and Ivokamet. 
The FDA is investigating other SGLT-2 inhibitor drugs, dapagliflozin and empagliflozin, for similar risks.
What is clear if nothing else, is that consumers must be proactive with regard to health, wellness, and if prescribed a drug for any reason, especially diabetes, they should research and question its efficacy and side effects. Of course, when it is also crystal clear that drug companies put profits above people, perhaps the best advice is to take care of oneself, eat a healthy diet and exercise. In this day and age, prevention should take precedence over medical intervention.
6. http://www.drugwatch.com/actos/treating-type-2-diabetes-with-medication/ Classes of drugs