By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
A More Effective Regimen for H. pylori Eradication
Source: Liou JM, et al. Lancet 2013; 381:205-213.
In the United States, peptic ulcer disease is caused primarily by two culprits: nonsteroidal anti-inflammatory drugs and Helicobacter pylori (and their combination). Evolution of pharmacotherapy for H. pylori currently employs combinations of amoxicillin (AMOX), metronidazole (METR), clarithromycin (CLAR), and a proton pump inhibitor (PPI). Unfortunately, over time H. pylori eradication rates with such regimens have fallen to as low as 80% or less. Is there a better way?
Liou at al randomized H. pylori-positive Taiwanese adults (n = 900) to one of three regimens — 1) Sequential 10 days: PPI + AMOX for 5 days followed by PPI + CLAR + METR for 5 days; 2) Sequential 14 days: PPI + AMOX for 7 days followed by PPI + CLAR + METR for 7 days; or 3) Standard 14 days: PPI + AMOX + CLAR for 14 days. The PPI used in this clinical trial was lansoprazole.
Adverse effect profiles of the three regimens were similar. Eradication rates were statistically significantly higher using sequential regimens (10 days = 87%, 14 days = 91%) than in standard regimens (82%).
Reflecting an increased recognition of problematic CLAR resistance at the end of the initial comparison trial, treatment failures from each regimen were assigned to receive an additional 14-day sequential course of treatment in which levofloxacin was substituted for CLAR. Eradication rates from this “rescue” population (regardless of which initial regimen they had received) were 80%.
Based on this large dataset, the authors suggest that sequential treatment regimens should become first line.
Uric Acid: How Much of a Bad Guy?
Source: Rosendorff C, et al. J Clin Hypertens 2013;15:5-6.
Uric acid (URA) has become the object of intense scrutiny of late, with more than its share of accusations linking it to hypertension and heart disease. The relationship between URA and gout is incontrovertible, though not necessarily universal. That is, in persons who develop gout, risk of future attacks is definitely related to absolute URA plasma levels. However, among persons without gout, elevations of URA appear to be well tolerated without evident toxicity in most: In asymptomatic adults with URA levels > 9.0 mg/dL, only about 5% per year go on to manifest acute gout.
The association of URA with hypertension, myocardial infarction, and even congestive heart failure is acknowledged. Whether this relationship is causal, and if a causal relationship is determined, whether lowering of URA will be beneficial remains to be determined. Remember the enthusiasm attendant to the recognition that homocysteine was associated with cardiovascular disease, heightened by the assurance that lowering homocysteine was simple and safe (B vitamins and folate), soon thereafter torpedoed by the interventional trials that failed to show improved outcomes in subjects whose homocysteine levels were reduced?
Despite the growing enthusiasm for criminalizing URA, we still do not have a large randomized, controlled trial indicating that modulation of URA improves hard endpoints. Until then, since all medications that reduce URA have their own bundle of potential misadventure to consider, we should watch and wait.
The Word ‘GPR40 Modulator’ May Soon be Entering Our Vocabulary
Source: Basu A, et al. Diabetes Care 2013;36:185-187.
The search for safe and effective agents to treat type 2 diabetes (DM2) continues, with hypoglycemia often being a limiting adverse effect of otherwise highly efficacious agents.
It has been observed that free fatty acids (FFA) play a role in glucose homeostasis, although the story line is complex. Acutely, elevations of FFA stimulate beta cell secretion of insulin. Chronic FFA elevations result in an impaired insulin response to high glucose levels, a phenomenon known as lipotoxicity.
The mechanism by which FFA impacts insulin secretion has been elegantly worked out and includes the G-protein-coupled receptor (GPR40). Because GPR is involved not only in insulin secretion, but also plays a role in obesity and dyslipidemia, its potential as a multimodal intervention has looked promising.
Studies in humans have shown that GPR40 agonists live up to the expectation that they lower glucose, with a very low risk of hypoglycemia. For instance, a head-to-head comparison with the sulfonylurea glimepiride found hypoglycemic episodes to be six-fold lower with the GRP40 agonist.
In an era of a burgeoning population of DM2 patients, we look forward to the addition of pharmacotherapies that safely complement our current options.