In 2012, the American Diabetes Association (ADA), along with the European Association for the Study of Diabetes (EASD), updated its treatment algorithm (originally released in 2009) that recommends an order of treatment for Type 2 diabetes. An algorithm is a set of steps to follow to achieve a desired end; in this case, the desired end is a diabetes regimen that keeps blood glucose levels in target range.
The algorithm recommends starting treatment at diagnosis with lifestyle changes (usually including an improved diet and more physical activity) and the drug metformin, then adding other blood- glucose-lowering drugs as needed. The effectiveness of any diabetes treatment is measured, in part, by a blood test known as the A1C, or HbA1c, test, which indicates average blood glucose level over the previous 2–3 months. The A1C level of people without diabetes tends to be between 4% and 6%, and the target for most people with diabetes is a test result lower than 7%.
The updated algorithm recommends that if a person newly diagnosed with Type 2 diabetes does not reach his target A1C level after three months of using metformin and lifestyle changes, his health-care provider add a drug from either the sulfonylurea, thiazolidinedione, GLP-1 receptor agonist, DPP-4 inhibitor, or basal insulin class. If a two-drug combination does not enable the person to reach his target A1C level in about three months, adding another drug from the classes listed above is recommended. And if combination therapy that includes basal insulin doesn’t result in achieving one’s target A1C level, initiating multiple daily doses of short- or rapid-acting insulin before meals is recommended.
Other drugs that are not included in the algorithm but that may benefit certain individuals include meglitinides, alpha-glucosidase inhibitors, colesevelam, bromocriptine, and pramlintide.
Metformin. Metformin works by limiting the release of glucose from the liver and also reducing insulin resistance, allowing the body to use insulin more efficiently. It carries a low risk of hypoglycemia (low blood glucose) and doesn’t tend to cause weight gain, a common side effect of many other diabetes drugs.
Sulfonylureas. The three most commonly used sulfonylureas are glimepiride (brand name Amaryl), glipizide (Glucotrol), and glyburide (Diabeta, Micronase). These drugs are known as “insulin secretagogues,” because they stimulate the pancreas to produce more insulin. Because sulfonylureas work by increasing insulin levels in the body, their most common side effects are hypoglycemia and weight gain.
Thiazolidinediones. Often referred to as “glitazones,” thiazolidinediones include pioglitazone (Actos) and rosiglitazone (Avandia); they work by reducing insulin resistance. However, because of concerns that rosiglitazone may increase the risk of heart attack, its use is restricted in the United States. Common side effects of these drugs include weight gain and fluid retention.
GLP-1 receptor agonists. These drugs, which must be injected, work by mimicking the actions of a natural hormone produced in the body called glucagon-like peptide-1 (GLP-1). They help lower blood glucose by causing the pancreas to produce more insulin following a meal and by decreasing production of another hormone, called glucagon, that signals the liver to release glucose. Use of these drugs often leads to weight loss. This occurs because they slow the rate at which food is moved from the stomach to the intestines, prolonging the feeling of fullness after a meal. They may also signal the brain to directly reduce feelings of hunger.
DPP-4 inhibitors. DPP-4 inhibitors work in a way similar to that of GLP-1 receptor agonists. But while those drugs mimic the naturally occurring hormone GLP-1, DPP-4 inhibitors block the action of an enzyme (known as DPP-4) that breaks down GLP-1 in the body. By slowing the effects of this enzyme, DPP-4 inhibitors allow GLP-1 to stay in the body longer (where the hormone increases insulin production and reduces the release of glucose from the liver).
Insulin. Insulin is the hormone that allows cells throughout the body to use glucose in the blood for energy. People with Type 2 diabetes often use insulin injections to overcome insulin resistance by increasing the amount of insulin in the body. The two broad categories of injected insulin are basal insulin, which provides a steady level of insulin throughout the day; and mealtime insulin, which is used to “cover” the expected rise in blood glucose following a meal. Compared with other drugs used to treat Type 2 diabetes, insulin has the greatest ability to lower blood glucose and A1C. That’s because unlike most drugs, doses of insulin can usually be increased (or decreased) to whatever level is needed to achieve desired results.
Meglitinides. This class of drugs works in a way very similar to that of sulfonylureas, leading to increased insulin production in the pancreas. However, meglitinides are short-acting, taking effect within 15–30 minutes of being ingested and lasting for only 4–6 hours. They should therefore be taken within 30 minutes of beginning a meal and are usually taken three times a day (but skipped if a meal is skipped).
Alpha-glucosidase inhibitors. This class of drugs slows the breakdown of complex carbohydrates, delaying the absorption of glucose from the digestive tract, and resulting in less of a rise in blood glucose level following a meal.
Colesevelam. This cholesterol-lowering drug is also approved to help lower blood glucose in people with Type 2 diabetes. It is believed to work by reducing the absorption of carbohydrates by the digestive system.
Bromocriptine. A special, quick-release formulation of bromocriptine is believed to lower blood glucose levels in people with Type 2 diabetes by helping to regulate the circadian rhythm (the normal cycle of hormones and other physiological processes throughout the day).
Pramlintide. Pramlintide is a synthetic version of amylin, a hormone that is normally released from the beta cells of the pancreas along with insulin. It is taken along with insulin before meals to regulate blood glucose levels after meals.
(Click here to learn more about drugs that are used for treating diabetes.)
What’s right for you
While the ADA recommends only certain treatments and the order in which they should be prescribed, its guidelines also recognize that people with diabetes have individual needs to which therapies should be tailored. If your blood glucose control is not where you want it or you’re troubled by side effects, there may be something else on the menu of options that’s right for you. Talk to your doctor, pharmacist, or diabetes educator if you have any questions or doubts about your current treatment.