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Medications for Diabetes

Darla is a forty-two-year-old woman fighting for her life—but not in the way you might think. She’s not tied to tubes and medication drips in an intensive care unit; instead, she’s confined to a wheelchair.

Darla knows that it didn’t have to turn out this way. As she gained weight into adulthood, her blood sugar crept up. When she was diagnosed with diabetes, she worried how it might affect her life—but not very seriously. She had a busy life with a stressful job, young children, and a strained marriage. Health was never her top priority. She was placed on one medication after another, but none of them turned things around. Some made her tired, while others caused weight gain or swelling. Most were expensive.

After the last oral medication failed to control her diabetes, she was prescribed insulin. The syringes and vials were hard to manage, as was remembering when to inject herself. She tried, she really tried, but things got worse. She suffered severe damage to the joints of her feet (Charcot joints), caused by repetitive trauma associated with loss of sensation due to uncontrolled blood sugars. The only effective treatment was complete rest. Previously full of energy and accustomed to running around chasing her kids, she was told to stay in a wheelchair for three months, then six, then for an indeterminate amount of time.

One afternoon, just after turning forty, she experienced pressure in her chest. She brought her kids to their activities and completed an errand or two—but something was definitely wrong. At the hospital emergency department, she was told she was having a heart attack and was whisked into the cardiac catheterization (“cath”) lab to have lifesaving stents placed in her heart. When she left the hospital, four new medications were added to her list.

She desperately wanted to walk again and was highly motivated to turn her diabetes around. By now, she was on whopping doses of insulin, which made her tired and packed on even more pounds. With each visit, she was told to take more insulin, even though her numbers improved only slightly. She wondered where it all had gone so wrong and what she could have done differently.

WHAT IS DIABETES?

Diabetes mellitus,^* a condition of elevated blood sugar with multiple metabolic consequences, has been recognized for centuries. Central to diabetes are problems with insulin, a hormone made by the pancreas that controls the transport and metabolism of sugar in the blood and throughout the body. Modern medicine recognizes two types of diabetes. In type 1, an autoimmune disease formerly called “juvenile diabetes,” there is a deficiency of insulin; regular injections of the hormone are lifesaving and necessary.

In the much more common type 2 diabetes, resistance to the effect of insulin develops in genetically predisposed people—there are many of them—in response to eating too much of the wrong kinds of food and being sedentary. Several strategies are available to temper, reverse, and even cure the condition. When detected and managed early, especially in the so-called pre-diabetes stage, type 2 diabetes is best managed by modifications of lifestyle that focus on diet, exercise, and stress management. Unfortunately, the vast majority of type 2 diabetics don’t even know they are at risk until the disease is more advanced and medications are necessary.

It’s no exaggeration to say that type 2 diabetes is now epidemic in our population. Its incidence has increased fourfold over the last thirty years, now affecting one in four US adults over age sixty-five. Worldwide prevalence was 171 million in 2000, and the World Health Organization predicts that number will increase to 366 million by 2030. The cost of diabetes in 2007 was estimated at $174 billion and growing. If you don’t now know somebody with type 2 diabetes, you probably soon will.

Diabetes is an enormous burden for those who suffer from it and often for family members, too. It affects your entire life, often requiring medications that have to be taken several times a day and careful attention to what you’re eating and how you are living. Worse, uncontrolled diabetes carries with it the possibilities of chronic pain, impaired ability to fight infections, blindness, heart disease, kidney failure, and other devastating complications.

For these reasons, medical providers take the management of diabetes seriously. Insurance companies and payers often tie clinicians’ performance and reimbursement to how well they take care of their diabetic patients. Treatment plans are provided to doctors, nurses, and other health professionals to help optimize care. Diabetes progression and severity are measured in a number of ways, including monitoring signs and symptoms for complications. Much importance is placed on results of a blood test for hemoglobin A1C (HgbA1C), which reveals the average blood sugar over the preceding three months. For most patients, the target HgbA1C is below 7 percent; below 5.7 percent puts an individual into the normal range. Every 0.1 percent change in the HgbA1C is significant.

DIABETES MEDICATIONS—AND THE PROBLEMS WITH THEM

Upon diagnosis of diabetes the prescription pad will often come out before lifestyle modification is discussed. Here are some of the likely medications, with their benefits and downfalls.

Metformin

The first-line medication for most diabetics, and even pre-diabetics, is metformin (Glumetza, Glucophage). Alone in its class, this drug works by decreasing the production and release of sugar from the liver, a mechanism that protects us from having dangerously low blood sugar (hypoglycemia). Metformin also sensitizes tissues to respond better and more effectively to insulin. Since it does not directly increase insulin secretion, it is not associated with hypoglycemia, a risk with other diabetes medications. Its use is common and its cost relatively low.

Nearly everyone started on metformin experiences side effects, though rarely serious ones. Gastrointestinal upset, with mild discomfort and loose stools, almost always occurs at the start of therapy or with an increase in dose. This generally passes within several days. A rare but more serious side effect is lactic acidosis—the build-up of excess acid in the system. This is most likely to occur when kidney function is impaired or in the presence of a kidney toxin, such as the contrast agents used in CT scans and other imaging studies. For this reason, metformin is often discontinued when a patient enters the hospital. If it’s restarted after discharge, gastrointestinal rumbling will probably return.

Many doctors are unaware that metformin causes vitamin B₁₂ deficiency in almost a third of people who take it. Those prescribed this medication should have their levels of vitamin B₁₂ checked regularly. Supplementation with vitamin B₁₂ is a good idea for people taking metformin, especially since there is little potential for toxicity even with high doses.

Sulfonylureas

These medications work by pushing out more of the body’s own insulin from the pancreas. A common side effect is hypoglycemia. Any increase in circulating insulin is also associated with weight gain. Sulfonylureas are widely prescribed and relatively inexpensive. Specific agents include glyburide (Micronase, DiaBeta, Glynase) and glipizide (Glucotrol).

But the sulfonylureas can be difficult to use. Besides causing weight gain, individual response to them is inconsistent. More serious is the possibility of pancreatic “burnout” resulting from the constant stress of being forced to release more and more insulin above physiologic demands. These drugs also interact profoundly with other blood-sugar-lowering medications (and herbs); both doctors and patients should be aware of those risks.

Thiazolidinediones

The thiazolidinediones (TZDs) are approved for both the prevention and treatment of diabetes. The two most prominent agents are rosiglitazone (Avandia) and pioglitazone (Actos). They work by increasing insulin sensitivity and decreasing circulating free fatty acids that have a direct effect on the metabolism of glucose. They were commonly prescribed in the past, until significant concerns about their adverse effects caused them to fall out of favor.

The saga of the TZDs is a cautionary tale. Soon after their release, they were associated with swelling in the legs and worsening of congestive heart failure, a serious condition in which the heart does not pump blood efficiently. Then an increased risk of bladder cancer was found in people on these medications.

There was more bad news to come. A 2007 summary of the known science on the safety of rosiglitazone stunned the medical community. Diabetics are at higher risk for heart disease than others, and this review paper indicated that taking rosiglitazone put patients at even higher risk of heart attacks. Given the gravity of this finding, doctors and patients alike backed away from using TZDs. In Europe, marketing of these medications was suspended by the European Medicines Agency, the equivalent of the US Food and Drug Administration. Subsequent reviews have suggested that this risk is lower than initially reported, but doubts persist, and use of rosiglitazone has plummeted.

Incretins

This group of medications is newer to the scene. They stimulate release of the body’s own insulin, but only in response to intake of a high glycemic load—that is, meals high in quick-digesting starches or sugars. They also slow gastric emptying and decrease the release of glucagon, another pancreatic hormone that opposes insulin and raises blood sugar. Use is common, as providers have moved away from the pancreas-depleting sulfonylureas and the potentially toxic TZDs. Medications in this group include sitagliptin (Januvia), saxagliptin (Onglyza), exenatide (Byetta, Bydureon), and liraglutide (Victoza, Saxenda). All are costly, although many insurance companies now favor their use and have lowered copays.

The initial, primary side effect of these medications is weight loss—not unwelcome among commonly overweight or obese diabetics. Sound too good to be true? Of course, it is. The incretins also cause nausea and diarrhea, as well as hypoglycemia, particularly when paired with other blood-sugar-lowering agents. Of greater concern is pancreatitis, a potentially life-threatening inflammation of the pancreas. A possible link to pancreatic cancer has also been suggested, though proponents of the medications argue that diabetes itself increases that risk. Some of these agents have been associated with thyroid cancer in animal models.

Despite recognized adverse effects and risks, the incretins are the current favored medications in those who don’t achieve adequate blood sugar control on metformin before going to insulin replacement.

Insulin

Insulin was isolated in the early twentieth century. Shortly thereafter, two scientists, Frederick Banting and John Macleod, won the Nobel Prize in Physiology or Medicine for their discovery of its therapeutic use in saving the lives of type 1 (insulin-deficient) diabetics; until that time, the diagnosis was universally fatal.

Insulin is now also commonly used to treat type 2 diabetes, if the medications described above fail to keep the condition in check. Its cost is variable, as it comes in many forms: ultra-long acting, long acting, regular, short acting, and ultra-short acting. Insulin must be injected or administered through a pump connected to a needle that remains in place throughout the day. It can be purchased over the counter in many states, though it more often requires a prescription. Typically, it is dosed to match the body’s natural fluctuations of insulin secretion in response to eating and activity.

Patients who use insulin must monitor their blood sugar carefully throughout the day. Side effects include potentially severe, even deadly, hypoglycemia if dosed too high. All patients on insulin gain weight—ironically, this means that their requirement for the hormone increases. It’s not uncommon for insulin-dependent diabetics to be caught in a perpetual cycle of insulin, weight gain, more insulin, more weight gain—leading to discouragement and frustration.

INTEGRATIVE MEDICINE APPROACHES TO MANAGING DIABETES

Given the downside of all the available drugs, many people with diabetes would prefer not taking medication and wonder if that is an option.

In fact, reversing type 2 diabetes is very possible—if it is not too severe. Every person with diabetes should focus on a careful diet, one that limits concentrated sweets or sweeteners and is high in fiber and vegetables. Optimal weight should be the goal, as excess weight and obesity make control of blood sugar more difficult. Current nutritional advice is to follow a low-glycemic-load diet, which means avoiding foods that provoke a rapid, high spike in blood sugar after eating. This requires learning the glycemic values for various foods. (There are many books and online sources of information on glycemic index and glycemic load, including The New Glucose Revolution for Diabetes by Jennie Brand-Miller, MD, and health.harvard.edu/healthy-eating/glycemic_index_and_glycemic_load_for_100_foods.)

Regular physical activity is good for all of us and is especially important for people with diabetes. Not only does it help keep blood sugar in the normal range, but it also offsets the risk for some of the serious complications of the disease, particularly heart disease. The minimum goal is two and a half hours per week of moderate-intensity aerobic exercise, defined as being unable to freely carry on a conversation while you’re doing it. Those not in the habit of exercising should start slowly, perhaps with the help of a trainer or health coach. It is good to complement aerobic activity with gentler forms of movement like tai chi and yoga.

Once diet and exercise are addressed, next steps might include the addition of supplements and botanicals known to lower blood sugar or mitigate diabetes complications. Some of the best studied and most promising include the following:

• Alpha-lipoic acid: While this supplement does not directly lower blood sugar, it helps restore insulin sensitivity and is effective in managing one common complication: peripheral neuropathy—the pain and numbness that develop most often in the feet and legs. Recommended dosing is 600 to 1200 milligrams daily.

• Capsaicin: A topical preparation of this compound, extracted from hot peppers, is also useful for neuropathy. It must be applied regularly four times daily.

• Berberine: Found in a number of plants (like the Oregon grape, Mahonia aquifolium), berberine improves blood sugar and retinopathy—the eye changes associated with diabetes that can lead to blindness. Take 200 to 300 milligrams two to four times daily after checking for drug interactions. Avoid in pregnancy.

• Chromium: This mineral can be used to lower blood sugar directly and reduce HgbA1C by an estimated 0.6 percent. The recommended dose is 1000 micrograms daily of chromium GTF. Avoid using higher doses, which can harm the kidneys and liver.

• Cinnamon: Known better as a culinary spice, this can be taken at concentrated doses of 1000 milligrams three times daily to lower blood sugar.

• Magnesium: One of the body’s most prominent minerals, magnesium is often deficient in diabetics. Supplementation to correct low levels can lower blood pressure and blood sugar. Start with 300 to 600 milligrams daily of magnesium glycinate or magnesium chelate, which are less likely to cause loose stools.

• Bitter melon: Extracts of this unripe fruit (Momordica charantia), much used in the cuisines of India, China, and southeast Asia, lower blood sugar.

• Prickly pear (Opuntia spp.): Extracts of both the fruit and pads of this cactus are used in Mexican folk medicine to treat diabetes; they have blood-sugar-lowering properties.

An integrative approach to diabetes includes stress management through such mind-body techniques as progressive muscle relaxation, guided imagery, mindfulness meditation, and hypnosis.

Traditional systems like Chinese medicine and Ayurveda also have much to offer for managing diabetes since it has been recognized as a disease for so long.

BOTTOM LINE

The impact of type 2 diabetes can be overwhelming. This is sad, considering how preventable the disease truly is. Our highly processed standard American diet and sedentary tendencies increase the likelihood that more and more people will develop it.

Medications for diabetes will always be needed, but they bring with them a burden of side effects and cost that could be avoided with appropriate changes in lifestyle. Our health care system and our society should encourage better lifestyle choices by making these choices more accessible and more affordable (as by subsidizing fruits and vegetables rather than commodity crops, for example). By changing diet, increasing physical activity, managing stress, and using natural remedies appropriately, most people with early and mild cases of type 2 diabetes can put the disease into complete remission, and many others will be able to keep their use of medications to a minimum.