The new guidelines emphasize tailoring treatment to the needs of specific patients.
After several years of preparation, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have released new guidelines on the management of hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The guidelines, which emphasize tailoring treatment to the needs of specific patients, were released online today in Diabetes Care
The guidelines note that glycemic management in T2DM is complicated by the increasing number of medications available to treat it, concerns about potential adverse consequences of these medications, and uncertainty regarding the microvascular and cardiovascular effects of intensive glycemic control. As a result, many clinicians are confused as to optimal treatment strategies.
The ADA’s “Standards of Medical Care in Diabetes” recommends reducing diabetes patients’ glycated hemoglobin (A1C) to less than 7.0% to reduce the incidence of microvascular disease. As long as hyperglycemia and significant side effects are guarded against, targets of 6.0% to 6.5% are considered appropriate for patients with recent disease onset, long life expectancy, and absence of cardiovascular disease. Targets of 7.5% to 8.0%, however, can be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbid conditions, or trouble meeting glycemic targets despite multipronged therapy.
Lifestyle interventions including modified diet, increased physical activity, and weight loss are critical for all diabetes patients. For highly motivated patients with an A1C less than 7.5%, the guidelines recommend pursuing lifestyle interventions for 3 to 6 months before starting medication.
Among the pharmaceutical treatments discussed by the guidelines are the following:
Metformin is the most widely used first-line medication for T2DM. It is considered weight-neutral, does not increase the risk of hypoglycemia, and may have cardiovascular benefits, although this is not entirely clear.
Sulfonylurea insulin secretagogues are effective at controlling blood glucose levels, but are associated with some weight gain and a risk of hypoglycemia. (Shorter-acting secretagogues may be associated with reduced risk of hypoglycemia but require more frequent dosing.)
Thiazolidinediones do not increase the risk of hypoglycemia and may be effective for longer than sulfonylureas and metformin. (One example, pioglitazone, showed a modest cardiovascular benefit in one trial, but has also been associated with a possible increase in risk of bladder cancer.)
Injectable glucagon-like peptide-1 (GLP-1) receptor agonists can cause moderate to significant weight loss, but can also cause nausea and vomiting.
Oral dipeptidyl peptidase-4 (DPP-4) inhibitors are weight-neutral. Neither they nor GLP-1 receptor agonists cause hypoglycemia by themselves.
Insulin replacement therapy is frequently required in T2DM, although not in as complex or intensive a fashion as in type 1 diabetes.
Although metformin is generally preferred as the most cost-effective initial agent for T2DM, if a patient’s A1C is more than 9.0%, 2 agents or insulin should be considered. If it is 10.0% to 12.0%, insulin should be strongly considered from the outset. If monotherapy does not achieve or maintain the patient’s A1C target during 3 months of treatment, then a second oral agent, a GLP-1 receptor agonist, or insulin should be considered. If the patient still makes no progress, then the new agent should be discontinued and replaced with another agent with a different mechanism of action. Adding a third noninsulin agent with a complementary mechanism of action may have some benefit, but the best option is to use insulin, especially if the patient’s A1C remains greater than 8.5%.
The guideline authors note that evidence of the comparative effectiveness of diabetes medications in achieving glycemic control is relatively slight, especially beyond monotherapy with metformin, and call for more and better research to provide more evidence in this vein.
To download a pdf of the guidelines, click here