Tier 1 includes metformin, the sulfonylurea class of drugs, long-acting (basal) insulin, and intensive insulin therapy, (using both long- and short-acting insulin). Tier 2 includes the drug classes of thiazolidinediones and GLP-1 receptor agonists. Other drugs that are not included in the algorithm but may benefit certain individuals include DPP-4 inhibitors, meglitinides, alpha-glucosidase inhibitors, colesevelam, and bromocriptine.
Metformin (brand name Glucophage and others) is considered to be the first-line drug for treating Type 2 diabetes. It works in several ways, the most important of which is limiting the release of glucose from the liver. Metformin also reduces insulin resistance, allowing the body to use insulin more efficiently. Some other benefits of metformin are that 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.
Because metformin is removed from the body by the kidneys, it should be used with caution by people with impaired kidney function. The most common side effects of metformin are nausea, diarrhea, gas, and abdominal pain. These side effects can be minimized by taking the drug with meals and by slowly increasing the dose from a low starting level. Metformin comes in many different doses and pill types; it is also available in liquid form for people who have trouble swallowing pills. Metformin can also be taken as part of a combination pill with a number of other drugs, allowing people who require both drugs to take fewer pills each day. Metformin has been shown to lower HbA1c — a measure of long-term blood glucose control — by 1% to 2%. The HbA1c level of people without diabetes tends to be between 4% and 6%, and the target level for most people with diabetes is 7%.
Sulfonylureas are a class of drugs often prescribed to people who are taking metformin but need a little more help to lower their blood glucose. The three most commonly used sulfonylureas are glimepiride (brand name Amaryl), glipizide (Glucotrol), and glyburide (Diabeta, Micronase). These drugs are known as “insulin secretagogues,” which means that they stimulate the pancreas to produce more insulin. They are generally taken by mouth once or twice daily.
Because sulfonylureas work by increasing insulin levels in the body, their most common side effects are hypoglycemia and weight gain. Sulfonylureas can lower HbA1c by 1% to 2%.
Insulin is the hormone that allows cells throughout the body to use glucose in the blood for energy. Because people with Type 2 diabetes have insulin resistance, insulin injections are often used to overcome this resistance by increasing the amount of insulin in the body. There are two broad categories of injected insulin: 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 (the mealtime dose is often called a bolus of insulin). Basal insulin can be a simple and effective treatment for Type 2 diabetes. The ADA recommends adding basal insulin to metformin for people who are not meeting their blood glucose goals on metformin alone, or on metformin plus a sulfonylurea.