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New injectable drugs work by targeting calcitonin gene-related peptide

A host of new medications that appear to prevent migraine headaches are in the final stages of testing and approval in the United States, according to a presentation at the annual meeting of the American Headache Society, held from June 8 to 11 in Boston.

The new injectable drugs work by targeting calcitonin gene-related peptide (CGRP). One, erenumab, works by blocking the receptor CGRP acts on, while other drugs (fremanezumab by Teva; eptinezumab from Alder Biopharmaceuticals; and galcanezumab from Eli Lilly and Co.) work by blocking CGRP itself.

In one phase 3 trial funded by Amgen, nearly 1,000 patients with episodic migraine were randomly assigned to one of two doses of erenumab or placebo for six months. Half the patients receiving monthly injections of the higher dose of erenumab experienced a 50 percent reduction in number of migraines, Peter Goadsby, M.D., Ph.D., a professor of neurology at King’s College London and the University of California, San Francisco, told HealthDay. In separate phase 2 trials testing erenumab’s safety in chronic migraine patients, the medication was also tied to fewer attacks.

For the other three medications, researchers reported results of phase 2 trials that tested the drugs’ safety. In each case, patients reported more headache-free days. Side effects, such as changes in blood pressure or potential liver damage, were found not to be a problem, researchers said. In addition, the drugs started working the first week of treatment. In some cases, patients were also able to cut back their other medications.

Study Warns of Diabetic Ketoacidosis With SGLT2 Inhibitors in T2D – Doubled risk compared with DPP4 inhibitors

The newest class of drugs for treating type 2 diabetes carries a greater risk for diabetic ketoacidosis compared to other classes of drugs, a new study suggests.

Newly initiated use of an SGLT2 inhibitor was associated with a roughly twofold greater risk of diabetic ketoacidosis versus new initiation of a DPP4 inhibitor (HR 2.2, 95% CI 1.4 to 3.6), according to Michael Fralick, MD, of Brigham and Women’s Hospital, and colleagues.

Findings were similar in an unadjusted model, while hospitalization for diabetic ketoacidosis (DKA) within 180 days of treatment initiation was around two-times higher with use of an SGLT2 inhibitor compared to a DPP4 inhibitor (4.9 events per 1,000 person-years versus 2.3 events per 1,000 person-years; HR 2.1, 95% CI 1.5 to 2.9).

The findings were published as a letter in The New England Journal of Medicine.

Following twenty case reports of diabetic ketoacidosis with this class of drugs, the FDA issued a warning in May 2015, and announced required label changes later that year after over 70 cases of ketoacidosis were reported.

In June 2016, the American Association of Clinical Endocrinologists and American College of Endocrinology published a position statement in Endocrine Practice stating that “DKA occurs infrequently and that the risk-benefit ratio overwhelmingly favors continued use of SGLT-2 inhibitors with no changes in current recommendations. However, DKA diagnosis may be missed or delayed due to atypical presentation involving lower-than-anticipated glucose levels or other misleading laboratory values,” ultimately recommending additional research on this association.

Fralick explained in a press release how he originally became interested in this relationship after one of his own patients on an SGLT2 inhibitor was hospitalized for diabetic ketoacidosis, stating, “My best research projects come from my patients — their experiences drive the questions I investigate.”

“This is a side effect that’s usually seen in patients with type 1 diabetes mellitus – not type 2 – so doctors are not ‘on the lookout’ for it. That means that the risk of this side effect might actually be even higher than what we found due to misdiagnosis/under recording.”

The research group collected data on 50,220 patients with type 2 diabetes from the TruvenMarketScan database of commercially insured patients. All patients were started on an SGLT2 inhibitor or DPP4 inhibitor prior to the FDA warning (April 2013-December 2014).

“DPP4 inhibitors were chosen as the comparator medication because they are similarly used as a second-line treatment for diabetes but have no known association with diabetic ketoacidosis,” the authors wrote.

Utilizing a Cox regression model, Fralick’s group applied a 1:1 propensity-scare matching system to equally match participants based on 46 various characteristics to assess frequency of hospitalizations for diabetic ketoacidosis within 180 days of treatment initiation.

The research group also noted that patients who were prescribed SGLT2 inhibitors tended to be younger with fewer coexisting illnesses, although were more likely to be placed on insulin compared to patients on DPP4 inhibitors.

The researchers strongly suggest healthcare providers be vigilant for signs and symptoms of this in their patients, and should also be a factor to consider at time of prescription. In terms of prevention, Tamler added that he advises patients on SGLT2 inhibitors to “remain well-hydrated and stay on top of their blood sugar levels.”

 

Link found between chocolate consumption and lower risk of atrial fibrillation.
A new study led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with researchers at the Harvard T.H. Chan School of Public Health and the Aalborg University and Institute of Cancer Epidemiology in Denmark, found that consuming moderate amounts of chocolate was associated with significantly lower risk of being diagnosed with atrial fibrillation (AF), a common and potentially life threatening type of irregular heartbeat. The findings were based on data collected and analyzed from a large study of men and women in Denmark.

The study was published online in the journal Heart.

“Our study adds to the accumulating evidence of the health benefits of moderate chocolate intake and highlights the importance of behavioral factors for potentially lowering the risk of arrhythmias,” said lead author Elizabeth Mostofsky, ScD, MPH, a postdoctoral fellow at BIDMC and an instructor in the Department of Epidemiology at Harvard T. H. Chan School of Public Health.

The study included 55,502 men and women participating in the Danish Diet, Cancer and Heath Study. The researchers obtained information on the study participants’ body mass index, blood pressure and cholesterol, which were measured when participants were recruited between 1993 and 1997. They also looked at participants’ health conditions, including high blood pressure, diabetes, or cardiovascular disease as well as data on their diet and lifestyle gathered from questionnaires. Using a validated questionnaire, the researchers collected information about the participants’ daily chocolate intake.

Among the participants recruited, 3,346 cases of AF occurred over a 13.5 year follow–up period based on data collected from the Danish National Patient Register. Compared with participants who ate a one–ounce serving of chocolate less than once per month, participants who ate one to three servings per month had a 10 percent lower rate of AF; those who ate one serving per week had a 17 percent lower rate; and those who ate between two and six servings per week had a 20 percent lower rate. The benefit leveled off slightly with greater chocolate consumption, with those eating one or more servings per day having a 16 percent lower AF rate on average. Results were similar for men and women.

“Despite the fact that most of the chocolate consumed by the study participants likely had relatively low concentrations of potentially protective ingredients, we still observed a significant association between eating chocolate and a lower risk of AF, suggesting that even small amounts of cocoa consumption can have a positive health impact,” Mostofsky said. “Eating excessive amounts of chocolate is not recommended, however, because many chocolate products are high in calories from sugar and fat and could lead to weight gain and other metabolic problems. But moderate intake of chocolate with high cocoa content may be a healthy choice.”

“This study adds to the growing body of evidence that, compared with other snacks or treats, eating small amounts of dark chocolate on a regular basis as part of an overall balanced, heart–healthy diet is a good option that may reduce the risk of cardiovascular disease,” said study author Murray Mittleman, MD, DrPH, a preventive cardiologist at BIDMC and professor of epidemiology at Harvard T.H. Chan School of Public Health.

First nasal spray therapy successful in treating paroxysmal supraventricular tachycardia.

An experimental nasal spray, etripamil, may benefit patients with paroxysmal supraventricular tachycardia (PSVT), according to a study presented at the annual meeting of the Heart Rhythm Society, held from May 10 to 13 in Chicago.

The phase 2 trial included 104 patients from the United States and Canada. The researchers said heart rate was controlled within 15 minutes in 87 percent of patients who received a 70-mg dose of the nasal spray; 75 percent of patients who got 105 mg; and 95 percent of patients given a 140-mg dose.

That compared to 35 percent of patients who received a placebo. The most common side effects of etripamil were temporary nasal congestion or irritation, according to the researchers.

“This study introduces a completely novel therapy that has never been used before, and has the potential to alter how we treat patients with PSVT,” lead author Bruce Stambler, M.D., a cardiac electrophysiologist at Piedmont Heart Institute in Atlanta, said in a news release from the Heart Rhythm Society. “Many patients who suffer from PSVT can experience sudden episodes anytime and anywhere. This fast-acting nasal spray therapy could give patients the convenience to self-administer treatment no matter the location and without having to go to the hospital.”

Several authors disclosed financial ties to medical device and pharmaceutical companies, including Milestone Pharmaceuticals, which manufactures etripamil.

Limited evidence for effectiveness, but considerable information on cardiac risks of domperidone.

The dopamine receptor antagonist domperidone, which may increase milk production in lactating women, is associated with serious cardiac risks, and should not be used for lactation enhancement, according to a commentary published in the June issue of Obstetrics and Gynecology.

Catherine A. Sewell, M.D., M.P.H., from the U.S. Food and Drug Administration in Silver Spring, Md., and colleagues discuss the safety issues associated with use of domperidone. The authors note that although domperidone is approved for certain gastrointestinal disorders in some countries, it is not approved for any human use in the United States, and is associated with serious cardiac arrhythmias. An FDA import alert was issued in 2004 and updated in 2012, explaining that domperidone import is illegal, with limited exceptions.

A public safety warning has been issued regarding use of domperidone for lactation; however, domperidone is sometimes obtained illegally and used by lactating mothers to increase milk production. Limited quality evidence is available for the effectiveness of domperidone in enhancement of lactation, while considerable evidence is available on the cardiac risks associated with domperidone, which include QT prolongation, torsades de pointes, and sudden cardiac death, including among lactating women.

“In light of limited efficacy data that do not offset safety concerns from a public health perspective, we continue to caution against using domperidone for lactation enhancement,” the authors write.

Higher doses independently linked to slower change in emphysema, especially among former smokers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) might play an important role in the prevention and treatment of emphysema, according to a study published in the May 1 issue of the Annals of the American Thoracic Society.

Megha A. Parikh, from Columbia University in New York City, and colleagues recruited 4,472 patients ages 45 to 84 years from the general population. The authors examined whether ACE inhibitor and ARB dose is associated with progression of percent emphysema by computed tomography (CT).

The researchers found that 12 and 6 percent of participants used an ACE inhibitor and ARB at baseline, respectively. At baseline, the median percent emphysema was 3.0 percent; over a median of 9.3 years the rate of progression was 0.64 percent. There was an independent correlation for higher doses of ACE inhibitor or ARB with slower change in percent emphysema (P = 0.03). Over 10 years the predicted mean increase in emphysema among participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percent, compared with 0.66 percent for those who did not take ARBs or ACE inhibitors (P = 0.01). The greatest magnitude of findings was seen among former smokers (P < 0.001).

“In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers,” the authors write.

Data from trials show weight loss is associated with HbA1c reduction in dose-dependent manner

For overweight and obese adults with type 2 diabetes (T2D), weight loss is associated with a reduction in hemoglobin A1c (HbA1c) in a dose-dependent manner, according to a review published online April 18 in Diabetes, Obesity and Metabolism.

Anders Gummesson, M.D., from Sahlgrenska University Hospital in Gothenburg, Sweden, and colleagues conducted a systematic review of the literature to identify prospective trials of energy-reduced diets, obesity drugs, or bariatric surgery in adult overweight and obese patients with type 2 diabetes. The authors developed a linear model to describe the effect of weight reduction on HbA1c based on data from three to 24 months of follow-up. Data were included for 58 articles with 124 treatment groups and 17,204 adults.

The researchers identified a linear relationship between weight loss and HbA1c reduction; for each 1 kg of reduced body weight there was an estimated mean reduction of 0.1 percent in HbA1c for the overall population. Baseline HbA1c significantly affected the correlation between weight loss and HbA1c: for the same degree of weight loss, high HbA1c at baseline correlated with a greater reduction in HbA1c. There were also weight-loss-dependent reductions in diabetes medication.

“This summary of data from previous trials regarding the effect of weight reduction on HbA1c may be used to support the design and interpretation of future studies that aim to demonstrate the efficacy of weight loss interventions for T2D treatment,” the authors write.

Certain medications seem safer than others, but overall danger is low, researchers say

Use of macrolides, quinolones, tetracyclines, sulfonamides, and metronidazole during pregnancy may increase the risk of miscarriage, according to a study published in the May 1 issue of CMAJ, the journal of the Canadian Medical Association.

Anick Bérard, Ph.D., a professor at the University of Montreal’s Faculty of Pharmacy, and colleagues matched 8,702 cases of spontaneous abortion with 87,020 controls by gestational age and year of pregnancy. The researchers used data from women ages 15 to 45 who were covered by Quebec’s drug insurance plan.

The team found that 16.4 percent of the women who had miscarriages were exposed to antibiotics during early pregnancy, compared to 12.6 percent of the controls. Azithromycin and clarithromycin were linked to a 65 percent and two-fold increased risk of miscarriage, respectively. Norfloxacin was associated with more than a four-fold increased risk.

“After adjustment for potential confounders, use of macrolides (excluding erythromycin), quinolones, tetracyclines, sulfonamides, and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion,” the authors write. “Our findings may be of use to policymakers to update guidelines for the treatment of infections during pregnancy.”