What’s New in Anti-Diabetic and Cardiovascular Drugs

Recent years have witnessed steady advances in the treatments for diabetes and cardiovascular disease, which remain among the foremost causes of death in the United States annually. Leading experts have long noted the strong link between the two diseases. According to the American Heart Association (AHA), heart disease and stroke are the No. 1 causes of death and disability among those with type 2 diabetes, and at least 65 percent of people with diabetes die from some form of heart disease or stroke. Plus, adults with diabetes are two to four times more likely to have heart disease or a stroke than those without diabetes. Because of the correlations between the two diseases, it makes sense to look at the current medicines being used to treat each of them when thinking about future treatments.

Diabetes and Cardiovascular Disease Today

Diabetes is the seventh leading cause of death amongAmericans, according to the Centers for Disease Control and Prevention (CDC). The American Diabetes Association (ADA) reports that 25.8 million children and adults have diabetes in theU.S., and seven million of them don’t even know it. In 2010 alone, 1.9 million new cases were diagnosed among people age 20 and older. Diabetes is most prevalent in the African-American community, with 12.6 percent coping with the disease.The ethnic breakdown for other communities includes 11.8 percent of Hispanics, 8.4 percent of Asian-Americans and 7.1 percent of whites who suffer from the disease. Diabetes hits the elderly population the hardest, with 26.9 percent of those age 65 and older diagnosed. Overall, 11.3 percent of the 20-and-older age group have the illness.

Cardiovascular disease is even more widespread in the U.S., with more than 81 million people having one or more forms of it, according to 2006 figures from the AHA.In fact, heart disease is the No. 1 cause of death in the U.S., the CDC says. And, the CDC reports that it’s the leading cause of death for most ethnicities in the U.S.: In 2004, 25.8 percent of AfricanAmericans, 19.8 percent of American Indians/Alaska natives, 24.6 percent of Asian-Americans, 22.7 percent of Hispanics and 27.5 percent of whites who died did so because of heart disease.

Heart Disease Medication

There are four types of cardiovascular disease, each with its own set of medications. The most common type, high blood pressure, is treated several different ways. To flush excess water and sodium from the body, diuretics are used. Beta-blockers reduce nerve impulses to the heart and blood vessels to make the heart beat slower and work less hard. Angiotensinconverting enzyme, or ACE, inhibitors prevent the formation of the hormone angiotensin II, which usually causes blood vessels to narrow.Angiotensin antagonists protect blood vessels from angiotensin II, which then leads to the vessels becoming wider. Calcium channel blockers, or CCBs, prevent calcium from entering the muscle cells of the heart and blood vessels, which causes the blood vessels to relax. However, CCBs have shown better results for African-Americans and older adults than ACE inhibitors or beta-blockers alone, according to recent studies. Alpha-blockers reduce nerve impulses to blood vessels, which allow blood to pass more easily. Alpha-betablockers are similar to alpha-blockers, but they also slow the heartbeat, like beta-blockers. This results in less blood being pumped through the vessels. Other medications that relax blood vessels are nervous system inhibitors, which control nerve impulses and cause the blood vessels to widen. Vasodilators open blood vessels by relaxing the muscle in the vessel walls.

The second most common form of cardiovascular disease is coronary heart disease. Aspirin is used to lower the risk of a heart attack for those who have already had one. In addition, aspirin has been shown to be effective in keeping arteries open in those who have had a previous heart bypass or similar artery-opening procedure. When pumping of the heart weakens, digitalis is prescribed to make the heart contract harder. Digitalis also slows some fast heart rhythms. Nitrates, including nitroglycerine, relax blood vessels and stop chest pain. Blood cholesterol-lowering agents like statins, niacin, fibrates and bile acid sequestrants are prescribed to lower LDL cholesterol levels in the blood. Thrombolytic agents are given during a heart attack to break up a blood clot in a coronary artery to restore blood flow.

Many of these medications also are used to treat coronary heart disease. In addition to alleviating blood pressure, ACE inhibitors help the damaged heart muscle pump blood better. Beta-blockers also assist with chest pain and ward off repeat heart attacks. Calcium channel blockers relax the muscles around the coronary arteries, which causes the blood vessels to open and increases blood flow to the heart. Diuretics also are used for treating coronary heart disease, since they decrease fluid in the body and help to reduce high blood pressure.

Strokes are the third most common type of cardiovascular disease. Aspirin is used as an antiplatelet/platelet aggregation inhibitor in stroke or transient ischemic attack, or TIA, patients. It also can reduce the risk of a patient having another TIA or stroke. Clopidogrel (Plavix) is an antiplatelet/platelet aggregation inhibitor that helps prevent another stroke by decreasing the blood’s clotting ability. Dipyridamole (Aggrenox, Persantine) is the combination of aspirin and extended-release dipyridamole, two antiplatelet/platelet aggregation inhibitors that prevent a future TIA or stroke. Heparin (Calciparine, Liquaemin), an anticoagulant drug, is sometimes used to reduce acute stroke damage or stroke risk in hospitalized patients and to lower the risk of blood clots forming in their leg veins. Ticlopidine (Ticlid), an antiplatelet, helps prevent another stroke. Tissue plasminogen activator (Activase) is a thrombolytic drug that lessens the severity of ischemic stroke if it is given within three hours of stroke onset. Warfarin (Coumadin) is an anticoagulant often prescribed for daily use to reduce the risk of stroke.

Heart failure is the least common of the four types of cardiovascular disease. Like the other cardiovascular diseases, ACE inhibitors are employed to assist those with heart failure. Examples include enalapril (Vasotec), lisinopril (Prinivil, Zestril) and captopril (Capoten). Angiotensin II receptor blockers, or ARBs (like losartan [Cozaar] and valsartan [Diovan]) have many of the same benefits as ACE inhibitors, providing an alternative for people who don’t respond well with ACE inhibitors. Aldosterone antagonists like spironolactone (Aldactone) and eplerenone (Inspra) are potassium-sparing diuretics that also help the heart pump more efficiently. They may reverse scarring of the heart and allow those with severe heart failure to live longer. Digoxin, or Lanoxin, as well as betablockers(such as carvedilol[Coreg], metoprolol[Lopressor] and bisoprolol [Zebeta]) and diuretics (bumetanide [Bumex] and furosemide [Lasix]) also are used for patients with heart failure.

Diabetes Medication

Due to the rise in the number of Americans with risk factors, such as excess weight, type 2 diabetes sufferers continue to increase as a percentage of the population — even as more lifesaving medications are being brought to market. Diabetes medication includes various types of insulin. Rapid-acting insulin — such as insulin lispro (Eli Lilly), insulin aspart (Novo Nordisk) or insulin glulisine (Sanofi-Aventis) — begins to work about five minutes after injection, peaks in an hour and continues to be effective for two to four hours. Regular- or short-acting insulin reaches the bloodstream within 30 minutes after injection, peaks after two to three hours and is good for three to six hours. Intermediate-acting insulin, which hits the bloodstream about two to four hours after injection, peaks four to 12 hours later and lasts for 12 to 18 hours. Long-acting insulin, which takes six to 10 hours to start working, lasts for 20 to 24 hours.

Insulin isn’t the only injectable drug that is used to treat people with diabetes. Pramlintide (Symlin) is a synthetic form of the hormone amylin, which is produced along with insulin by the beta cells in the pancreas. It helps maintain normal blood glucose levels. Exenatide (Byetta) is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics.A synthetic version of the naturally occurring hormone exendin-4, exenatide lowers blood glucose levels by increasing insulin secretion.

There are six types of oral medications that can alleviate the effects of diabetes. Sulfonylureas (such as chlorpropamide [Diabinese], glipizide [Glucotrol and Glucotrol XL], glyburide [Micronase, Glynase, and Diabeta] and glimepiride [Amaryl]) and meglitinides (repaglinide [Prandin] and nateglinide [Starlix]) stimulate the pancreas’ beta cells to release more insulin. Biguanides, like metformin (Glucophage), lower blood glucose levels by decreasing the amount of glucose produced by the liver. Thiazolidinediones (rosiglitazone [Avandia] and pioglitazone [ACTOS]) help insulin absorption in muscle and fats and also reduce glucose production in the liver. Alpha-glucosidase inhibitors assist the body in lowering blood glucose levels by blocking the breakdown of starches in the intestine and slowing the breakdown of some sugars.A new class of oral medications, DPP-4 inhibitors, improve A1C without causing hypoglycemia. Types like sitagliptin (Januvia) and saxagliptin (Onglyza) work by preventing the breakdown of a naturally occurring compound in the body called GLP-1.

Aspirin, which as mentioned earlier significantly lowers the risk of repeat heart attacks, also may benefit those with diabetes more likely to suffer from a heart attack. It addition, it can aid diabetes sufferers who already have had a heart attack or a stroke, or who have heart disease. However, the long-term benefits for aspirin use for this population are not yet known. For example, its effects have not yet been studied in people under age 30.

Aside from insulin, similar injectables and oral medication, people with diabetes have to take steps to prevent getting the flu. According to the ADA, people with diabetes are about three times more likely to die from the flu and pneumonia. To lessen the risk, people with diabetes are advised by the ADA to receive flu shots each year and pneumonia vaccine as frequently as recommended by their physician.

The Evolution of Heart Disease Medication

The resounding success of Pfizer’s Lipitor and the difficulty of topping the drug as the world’s best-selling medicine have caused many drug companies to veer away from heart disease and focus their drug development efforts on other ailments. Even Pfizer itself has dropped heart disease on its list of priorities. Warfarin has been considered the primary blood thinner, but the recently approved dabigatran has emerged as a contender. Developed by Boehringer Ingleheim GmbH and marketed under the brand name Pradaxa, it has proved, according to the company, to be more effective than warfarin in preventing stroke in patients with atrial fibrillation. Johnson & Johnson has created its own answer to warfarin, rivaroxaban.The not-yetapproved medication is said to help prevent strokes and avoid bleeding complications in patients with atrial fibrillation. Going up against Pradaxa for anti-clotting are xarel to from Bayer and Johnson & Johnson and apixaban from Bristol-Myers Squibb and Pfizer. Merck’s experimental pill, vorapaxar, is supposed to have the same effects as a blood thinner, lowering the risk of heart attack and stroke, but without excessive bleeding. Merck also is testing a pill called anacetrapid, a CETP inhibitor that is supposed to reduce bad (LDL) cholesterol by 40 percent and raise good (HDL) cholesterol by 138 percent.

AstraZeneca will challenge Plavix, the second-best-selling drug worldwide, with Brilique. The makers claim that studies show it more effectively cuts the risk of heart attacks, strokes and death linked to heart disease than Plavix. Brilique is set to be sold in the European Union later this year. While the FDA had delayed approval for the oral anti-platelet medication, which is to be marketed as Brilinta in the U.S., it is set to rule this summer on AstraZeneca’s reapplication for the agent’s approval. Another Plavix challenger is Novartis’ and Portola’s elinogrel, which is in final-stage testing. The experimental blood thinner was found to work quickly in patients who had surgery to unblock an artery.

Trials have just started in the United Kingdom for a daily polypill that is supposed to reduce the risk of heart attacks and strokes. Made by the India-based company Cipla, the polypill is a combination of five low-dose generic drugs. Since those five generic drugs are well-known and are usually prescribed with one another, it will likely be easier for makers to get the polypill on the market while also reducing costs for lowincome patients in the U.S.

The Evolution of Anti-Diabetic Medication

Most of the new anti-diabetic medicines that have been coming out are for type 2 diabetes and they are once-a-week treatments instead of the traditional daily or twice-a-day options. Three long-acting glucagon-like peptide-1 receptor agonists, Eli Lilly’s dulaglutide, GSK’s albiglutide and Sanofi-Aventis’ lixisenatide, are in Phase III testing. Roche’s aleglitazar, a dual PPAR agonist, also shows promise for the management of cardiovascular disease in high-risk patients, though it must undergo testing.

A different kind of drug in Phase III trials is Bristol-Myers Squibb and AstraZeneca’s dapagliflozin, a renal sodiumdependent glucose transport (SGLT-2) inhibitor, under development for the treatment of type 1 and 2 diabetes. Glucose is usually removed from the bloodstream by glomerular filtration, but it’s subsequently reabsorbed through active transport mechanisms in the proximal convoluted tubule. Tubular reabsorption is done by two sodium-glucose co-transporters, SGLT-1 and SGLT-2, with the latter accounting for about 90 percent. Reabsorption occurs in diabetic patients and healthy people, the opposite of what is needed, which is why inhibition of SGLT-2 reduces the risks associated with diabetes. Aside from helping patients lower blood sugar, SGLT-2 inhibitors also have been shown to help patients lose weight.

The Future of Treatment

A lot of work is left to be done to battle diabetes, both to prevent it and stop it, says Dr. Robert Henry‚ professor of medicine‚ Department of Medicine‚ Division of Endocrinology and Metabolism at the University of California‚ San Diego‚ and president‚ Medicine & Science of the ADA: “We’d love to have a world free of diabetes, but it’s not happening.With our current changing lifestyles, I see the epidemic of diabetes escalating.” He adds that it will take a major commitment to research in this area to effect major change

“The positive side is that we’ve come a terrific long way,” he says. “The downside is we have a long way to go for type 1 and 2 diabetes. But the goal is to stop the disease, and I think that’s a reasonable goal. It’s going to come in small steps. The most important thing is that we don’t stop doing research — once we do that, we have no hope of those advances.”

Dr. Harlan Krumholz, professor of cardiology, epidemiology and public health at the Yale University School of Medicine and AHA spokesman, strikes a similar note about heart disease treatments, saying that big strides have been made against heart disease, but that hard work lies ahead in future treatment. “I think we need to improve our systems of care,” Krumholz says. “I still think there are ways to think we can do better, but the innovation has to be better than it has been in the past. The bar’s been raised, the industry knows that. In order for it to be good, it has to be really good and safe.”

Ironically, the strides that have been made in reducing risk factors make it harder to treat heart disease with medication, Krumholz says. “We recognize the success of lifestyle changes and lowering risk,” he says. “The challenge of new medications is coming on top of that. Even if you have a significant reduction in risk, you’ll have a harder time in gains. That raises the bar on the drugs; it makes it more difficult. You almost have to have a bigger impact to treat it because the overall numbers have gone down.”

Striking a note that’s both worrisome and promising about the possibilities still available for progress, Krumholz says that we still have a long way we can go in the treatment of heart disease. “It’s a tribute to the companies and the profession that we made so much progress, but we’re only halfway done with the success,” Krumholz says. “At the end of the day, when the final story is told, we are more toward the beginning than we are toward the ending of fighting this disease.”