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.