Focus of Research for Clinicians

A systematic review of 166 clinical studies published between January 1966 and April 2010 examined the comparative effectiveness, benefits, and adverse effects of available monotherapy and two-drug combinations of medications for adults with type 2 diabetes (see list of type 2 diabetes medications studied). The review did not cover treatment of type 1 diabetes or gestational diabetes nor does it review evidence regarding the effectiveness of diet, exercise, and weight loss. The full report, listing all studies, is available at http://www.effectivehealthcare.ahrq.gov/diabetesmeds.cfm. This summary, based on the full report of research evidence, is provided to inform discussions with patients of options and to assist in decisionmaking along with consideration of a patient’s values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Table

Type 2 Diabetes Medications Studied by Class With Abbreviations.

Background Information

The management of hyperglycemia is an important focus of treatment to achieve improved macrovascular and microvascular outcomes in patients with type 2 diabetes. Controlling blood-glucose levels often requires several strategies, including weight loss if needed, dietary control, increased physical activity, and antidiabetic medications.¹

Treatment regimens include single drugs and combinations of drugs from different classes. Choosing among the available medications requires consideration of benefits, adverse effects, mechanism of action, and cost. In 2007, the Agency for Healthcare Research and Quality published its first systematic review on the comparative effectiveness of oral medications for type 2 diabetes. The 2011 update includes newer medications and two-drug combinations.

Conclusion

Evidence on the comparative effectiveness of antidiabetic medications for long-term macrovascular and microvascular outcomes is limited. However, evidence is available on intermediate outcomes. Many antidiabetic medications given as monotherapy work equally well to lower blood glucose. Two-drug combinations decrease hemoglobin A1c (HbA1c) further. Most agents (except metformin [MET] and glucagon-like peptide-1 [GLP-1] receptor agonists) are associated with increases in weight. The risk of mild to moderate hypoglycemia varies—it is highest for second-generation sulfonylureas (SU) and is increased for some two-drug combinations over monotherapy. MET may cause gastrointestinal (GI) upset. A United States Food and Drug Administration (FDA) warning indicates that thiazolidinediones (TZD) are associated with increased risks for cardiac failure, cardiovascular events, hip and nonhip fractures, and other risks in some patients. Tables 1, 2, and 3 summarize evidence about benefits, adverse events, and long-term benefits.

Clinical Outcomes Table 1

Benefits. (Findings followed by evidence on specific comparisons.)

Clinical Outcomes Table 2

Adverse Events. (Findings followed by evidence on specific comparisons.)

Clinical Outcomes Table 3

Long-Term Benefits. (Findings followed by evidence on specific comparisons.) Studies examining long-term benefits were limited. Only low levels of evidence were available for long-term outcomes (except as noted below for Pio, which may provide benefit (more...)

Clinical Bottom Line

(Detailed comparisons: Tables 1, 2, 3)

Gaps in Knowledge

• Studies are needed to address the efficacy of treatments for hyperglycemia in patients with type 2 diabetes who have varying levels of underlying cardiovascular and renal disease, who come from different ethnic groups, or who have variant forms of type 2 diabetes.
• Additional comparative studies are needed, including comparisons of newer medications, combinations with basal or premixed insulin and MET or other oral agents, and additional two-drug combinations.
• Sufficient data on event rates are needed to analyze major clinically important outcomes, adverse events, and long-term complications of type 2 diabetes.

Average Wholesale Prices for Diabetes Medicines

What To Discuss With Your Patients

• Establishing a goal for HbA1c and strategies to help accomplish that goal, including weight loss, exercise, and consistent use of medication.
• Strategies to increase adherence, including creating a medication schedule, addressing the costs of medications, and reporting adverse effects in a timely manner.
• The need for regular glucose testing and routine blood tests for HbA1c.
• What side effects to expect from the chosen medicines, and when to contact you if side effects occur.

Resource for Patients

Medicines for Type 2 Diabetes, A Review of the Research for Adults is a companion to this clinician research summary. It can help people talk to their health care professionals about medications for type 2 diabetes. It provides information about:

• Types of diabetes medications.
• The benefits and risks of medications.
• Costs of medications.

Ordering Information

For electronic copies of Medicines for Type 2 Diabetes, A Review of the Research for Adults, this clinician research summary, and the full systematic review, visit www.effectivehealthcare.ahrq.gov/diabetesmeds.cfm. To order free print copies, call the AHRQ Publications Clearinghouse at 800-358-9295.

Source

The information in this summary is based on Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update, Comparative Effectiveness Review No. 27, prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-02-0018 for the Agency for Healthcare Research and Quality, March 2011. AHRQ Publication No. 11-EHC038-EF. Available at: www.effectivehealthcare.ahrq.gov/diabetesmeds.cfm. This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX.