New guidelines compare oral agents for diabetes management

An estimated 50.8 million people in India are living with diabetes, according to the World Diabetes Foundation. Diabetes results in complications ranging from retinopathy and neuropathy to coronary artery disease.

Epidemiological demand combined with increased complexity of care make evidence-based treatment guidelines vital for busy clinicians. The American College of Physicians (ACP) has published summary guidelines on use of oral agents for the management of type 2 diabetes mellitus based on a systematic review by the United States’ Agency for Healthcare Research and Quality (AHRQ).

The guidelines summarize head-to-head comparisons of monotherapy and dual-therapy regimens to determine[s2If !is_user_logged_in()]…

[/s2If][s2If is_user_logged_in()] superiority in glycemic control, mortality, and adverse effects, and other areas. Eleven classes of drugs were included with a focus on metformin, thiazolidinediones (TZDs), sulfonylureas, DPP-4 inhibitors, and GLP-1 agonists.

Based on 104 studies, the authors found that most oral diabetes agents are similar in efficacy (HbA_1c-lowering) overall. However, pooled data demonstrated the superiority of metformin as monotherapy. All dual regimens proved to be more efficacious than any one agent. Furthermore, metformin resulted in greater weight loss compared with TZDs, sulfonylureas, or DPP-4 inhibitors, while sulfonylureas resulted in weight gain.

There were 74 trials examining the effects of oral diabetes agents on lipids, most of which showed modest effects on LDL and HDL and moderate effects on triglycerides. Monotherapy with metformin resulted in larger reductions in LDL. Interestingly, adding a second drug to metformin did not result in increased benefit. In terms of HDL, TZDs were superior to metformin, and for triglycerides, metformin did better than sulfonylureas or TZDs.

Mortality is generally very challenging to prove, but 66 studies looked at long-term outcomes. Eleven observational studies found that metformin was associated with lower all-cause mortality compared with sulfonylureas.

Of course, efficacy must be balanced with safety. In terms of hypoglycemia, pooled results demonstrated that sulfonylureas increased the risk of hypoglycemia compared with other agents. The combination of metformin and a sulfonylurea increases the risk of hypoglycemia by 6-fold compared with metformin and TZDs. Metformin resulted in more gastrointestinal adverse effects, including diarrhea and dyspepsia, when added to other agents. Both heart failure and bone fractures were associated with TZDs.

Based on these findings, ACP recommends the use of metformin as initial therapy for most patients with type 2 diabetes and the addition of a second agent to further reduce hyperglycemia.

Source: Qaseem A, Humphrey L, Sweet D, et al. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2012;156:218-231.

The World Diabetes Foundation. http://www.worlddiabetesfoundation.org/ composite-35.htm. Accessed May 23, 2012.

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http://www.annals.org/content/156/3/218.full
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