Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.

For type 2 diabetes, after metformin, what next?

Source: Phung OJ, et al. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA 2010;303:1410-1418.

In the absence of contraindications, metformin is the preferred initial treatment for most patients with type 2 diabetes (DM2). Unfortunately, monotherapy is unlikely to maintain adequate glycemic control, requiring additional treatment. Although the addition of insulin to metformin is an appropriate next step, and has been labeled Tier 1 in the most recent guidelines published by the American Diabetes Association, some patients are reluctant to use insulin, and the considerable weight gain experienced by some insulin users, as well as risk of hypoglycemia, is problematic.

Among the non-insulin therapeutic choices, there is a great degree of variation in tolerability issues, such as amount of weight gain and frequency/severity of hypoglycemia that may help guide treatment decisions. Phung et al analyzed data from 27 randomized controlled trials (n = 11,198), most of which were 6 months or less in duration, to compare weight changes and hypoglycemia when non-insulin agents were added to metformin.

As might be anticipated, when TZDs, sulfonylureas, and glinides were added to metformin there was a 1.8-2.1 kg weight gain. GLP-1 mimetics, alpha-glucosidase inhibitors, and DPP-4 inhibitors were either weight-neutral or associated with minimal weight loss. Sulfonylureas were associated with higher rates of hypoglycemia.

Of course, progressive treatment of DM2 must be individualized, and should include consideration of characteristic tolerability issues such as weight gain and hypoglycemia.

Suicide risk with anticonvulsants

Source: Patorno E, et al. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA 2010;303:1401-1409.

Although the term "anticonvulsant" is indicative of a therapeutic class, pharmacologically the class is diverse. Despite dissimilarities, an analysis by the FDA (2008) discerned a relative doubling of suicide behavior/ideation in those receiving anticonvulsants compared to placebo, resulting in a change in labeling.

The HealthCore Integrated Research Database provides data with which to assess the relative risk for suicidal acts in persons receiving a variety of anticonvulsant agents. During a 5-year interval (2001-2006), almost 300,000 new prescriptions for various anticonvulsants were documented in this population. When compared to treatment with either topiramate or carbamazepine (reference drugs), important distinctions emerged in reference to suicidal acts and violence. For instance, the hazard ratio for suicidal acts was 1.42 for gabapentin, 1.84 for lamotrigine, and 1.65 for valproate, compared to topiramate.

The mechanism by which some anticonvulsants incur an increased suicide risk is not known, despite the recognition that anticonvulsants can have impact upon mood. The first 2 weeks after initiation is recognized to be a higher risk period. Clinicians should be vigilant for behavior or mood changes in patients treated with anticonvulsants, and note the lesser apparent risk for topiramate or carbamazepine.

Best use of home BP monitoring

Source: Pickering TG, et al. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc HTN 2010;4:56-61.

The largest body of information guiding treatment of hypertension (HTN) is based upon office BP management. Nonetheless, home BP monitoring (HBPM) is documented to be a better predictor of CV risk than office BP. For instance, patients with high office BP but low HBPM are recognized to be at substantially lower risk than office BP predicts; similarly, high HBPM pressures compared to office BP portends greater risk than indicated by office BP alone. Simply the fact that HBPM offers the opportunity for many more BP readings than is readily accessible in clinical care provides both a more comprehensive and consistent BP profile.

Recording HBPM twice daily (morning and evening), when averaged over 1 week, provides a sufficient BP profile to help guide management. By HBPM, HTN is > 135/85 mmHg and normotension is < 125/75 mmHg. Borderline HBPM (125-135/75-85 mmHg) merits consideration of 24-hour ambulatory BP monitoring for further clarification. The authors, writing on behalf of the American Society of Hypertension, provide a list of validated home BP monitoring devices at: