DDW: Obesity Surgery Through the Mouth Seems to Work

CHICAGO, June 3 — Transoral methods for reducing gastric volume or bypassing the stomach altogether as treatment for obesity are gaining steam, several reports here indicated.

Endoscopic suturing procedures have produced losses of more than 60% of excess weight in obese teens with up to 18 months of follow-up, and up to 40% after nine months in adults, two researchers said here at Digestive Disease Week in separate presentations.

And yet a third researcher reported that an implanted plastic food bypass tube, extending from the base of the esophagus to 100 cm (about 40 inches) into the small intestine, led to excess weight losses averaging 40% in a 12-week pilot study.

All three researchers reported few or no complications and noted that the procedures can be reversed easily if that proves to be necessary.

One of the studies was a follow-up of preliminary findings reported at DDW last year by Roberto Fogel, M.D., of Mercy Hospital in Miami and Hospital de Clinicas in Caracas, Venezuela. (See DDW: Stomach Suturing Via Oral Route Reduces Teen Obesity)

At that time, Dr. Fogel had reported six-month results for 12 teens, ages 14 to 17. The teens had lost an average of 60% of their excess weight.

His endoscopic procedure stitches the stomach walls together to create a narrow tube-like passage from the esophagus to the duodenum.

His new report covered 21 adolescents, 13 to 17 years old, with initial mean body mass index (BMI) of 36.2 before the procedure. Follow-up in this group ranged from six to 18 months.

Among all the teen patients, mean excess weight loss at six months was 67.3% (SD 15.6%).

For 15 patients with one year of follow-up and eight with 18 months of follow-up, excess weight loss averaged 63.8% (SD 16.7%) and 58.8% (SD 17.5%), respectively.

Christopher Thompson, M.D., of Brigham and Women’s Hospital in Boston, reported comparable findings with another endoscopic suturing procedure performed in 18 adults.

These patients averaged 41 years of age and had a baseline BMI of 38.7.

Dr. Thompson reported the following mean excess weight losses at various follow-up exams:

Three months (17 patients) 30.0%
Six months (15 patients) 30.3%
Nine months (seven patients) 34.2%

Although these percentages are half those seen in Dr. Fogel’s study of teens, the two researchers agreed that they actually reflect similar clinical effects. The apparent disparity is an artifact of how excess weight is calculated in teens versus adults.

The degree of weight loss in both studies is similar to that seen with Roux-en-Y bypass surgery in these populations, Drs. Fogel and Thompson agreed.

Dr. Fogel said his procedure takes about 40 minutes; about two hours was the average reported by Dr. Thompson, whose procedure involves an investigational full-thickness suturing device.

Another approach was reported by Paul Swain, M.D., of Imperial College London.

He presented findings from an initial clinical study of a polyethylene tube with a proprietary biocompatible coating.

The tube is anchored at the esophageal base with metal barbs at one end, and extends through the stomach about 100 cm into the small bowel, with similar anchors at the distal end.

Consequently, food passes directly from the esophagus into the intestine.

“People don’t need a stomach,” Dr. Swain said, pointing out that patients survive readily following total gastrectomy.

He said the 12-patient pilot study was primarily to assess safety. It was implanted for 12 weeks and then removed.

Mean excess weight loss was 40% at the time the devices were removed. Mean BMI at baseline ranged from 37 to 50.

“All tissue anchors remained in place and no spontaneous detachments occurred,” Dr. Swain reported. There were no serious complications associated with the device or its removal.

He said a six-month study was now underway and appeared to be showing similar results.

Dr. Fogel said the chief concern about devices in the GI tract is that they migrate. Bleeding from the anchors is another problem, he said.

“The best use [of devices] may be to use them for a year before surgery so that patients lose weight,” he suggested.

He said extreme obesity often complicates endoscopic or other surgery. Using an implanted device to help patients slim down before a more definitive procedure is performed may be the optimal approach, Dr. Fogel suggested.

Kai Nishi, M.D., of Cedars-Sinai Medical Center in Los Angeles, said it was currently unclear which type of transoral gastric reduction might be preferable.

Dr. Nishi is an investigator on a large clinical study of a procedure called Toga, which uses a proprietary transoral stapling device to reduce stomach volume.

He showed a video of the procedure, but indicated that results would not be available until next year.

Referring to this and the other studies reported at DDW, he said, “It will take these trials to determine which of these is optimal for safety and efficacy.”

Dr. Thompson’s study was funded by Bard.

Dr. Thompson reported relationships with Bard, Boston Scientific, Covidien, Olympus America, Power Medical, USGI Medical, and Valentx.

Dr. Swain’s study was funded by Valentx.

Dr. Swain reported no conflicts of interest other than research support from Valentx.

No external support was reported for Dr. Fogel’s study.

Dr. Fogel reported a consulting relationship with Davol.

Dr. Nishi reported relationships with Ethicon and Allergan.

Primary source: Digestive Disease Week

Source reference:
Fogel R, et al “Trans-oral vertical gastroplasty as a viable treatment for childhood obesity — a study of 21 adolescents with up to 18 months of follow-up” DDW 2009; Abstract S1426.

Additional source: Digestive Disease Week

Source reference:
Thompson C, et al “Transoral gastric volume reduction as an intervention for weight management (TRIM) multicenter feasibility study: a report of early outcomes” DDW 2009; Abstract M1259.

ASCO Breast: PODCAST: New Conference Debuts

(appx. 5 mins)In this exclusive Medpage Today podcast, staff writer Crystal Phend sits down with co-chairs of the inaugural American Society of Clinical Oncology (ASCO) Breast Cancer Symposium, Eric P. Winer, M.D., of the Dana-Farber Cancer Institute, and Clifford A. Hudis, M.D., of the Memorial Sloan-Kettering Cancer Center, to discuss the new entry in the medical conference arena.

Single Zometa Infusion Beats Two Months of Oral Therapy for Paget’s

AUCKLAND, New Zealand, Aug. 31-One Zometa (zoledronic acid) infusion for 15 minutes tops two months of oral Actonel (risedronate) for treatment of Paget’s disease of bone, say researchers here.

The study by Ian R. Reid, M.D., of the University of Auckland and colleagues at Novartis, maker of Zometa, and other centers in Europe and North America, was published in the Sept. 1 New England Journal of Medicine. The study was funded by Novartis.

Bisphosphonate therapy with agents such as Actonel and Zometa is the most common form of treatment for Paget’s disease. The disorder is characterized by a dramatic increase in bone turnover and resorption, leading to bone pain, skeletal deformities, pathologic fractures, arthritis, neurologic complications and deafness.

The researchers carried out two identical randomized trials comparing the effects of Zometa with those of Actonel on biochemical markers of disease activity and quality of life.

A total of 357 men and women with radiologically confirmed Paget’s disease were enrolled. They were randomly assigned in a double-blind fashion to receive either one infusion of Zometa at 5 mg over 15 minutes followed by placebo tablets for 60 days, or a sham (saline) infusion followed by 30 mg of Actonel four times a day for 60 days. All patients also received 1 g of calcium and 400 U to 1000 U of calcifreol per day.

The primary endpoint was the proportion of patients with a therapeutic response, which was defined as either normalization of the alkaline phosphatase (ALP) level or a reduction of at least 75% in excess ALP at six months.

Secondary endpoints included biochemical markers of bone resorption and formation, and quality of life based on responses to a standardized questionnaire.

The investigators found that at six months, 169 of 176 (96%) of patients receiving Zometa had a therapeutic response, compared with 127 of 171 (74.3%) of patients receiving Actonel (P

CDC Recommends Deferring Hib Booster Shots in Light of Vaccine Shortage

ATLANTA, Dec. 20 — In the wake of the recall of a million doses of Haemophilus influenzae type B (Hib) vaccine, the CDC has asked physicians to delay booster vaccinations for most children.

“Because of the short-term reduction in available doses of Hib-containing vaccines, CDC, in consultation with the Advisory Committee on Immunization Practices, the American Academy of Family Physicians, and the American Academy of Pediatrics, recommends that providers temporarily defer administering the routine Hib vaccine booster dose administered at age 12 to 15 months except to children in specific groups at high risk,” said a special dispatch from Morbidity and Mortality Weekly Report.

A CDC spokesperson said the delay in boosters is meant to conserve the available doses for infants slated for their primary Hib vaccinations.

The vaccine is indicated for administration in a two- to three-dose primary series at two to six months of age, followed by a booster at 12 to 15 months.

“Short-term deferral of the booster dose among children ages 12 to 15 months is not likely to result in an increased risk for Hib disease,” the CDC said. It expects that continued immunity from the primary series, plus the current low level of Hib colonization in the general population, will combine to give adequate protection until the vaccine supply is fully restored.

The new recommendations call on physicians to keep track of patients whose boosters are deferred and recall them when the supply has recovered.

The CDC also said clinicians should “order only the number of doses of vaccine required to meet immediate needs (i.e., a supply for up to four weeks) and should refrain from attempting to build an inventory of Hib vaccine.”

On Dec. 12, Merck and the FDA announced a voluntary recall of one million doses of the company’s Pedvax HIB and Comvax products due to bacterial contamination problems at the manufacturing plant earlier this year.

“I think they’re handling it the best way they possibly can,” commented Vivian Lennon, M.D., the director of primary care services of Children’s Health of Atlanta.

“They’ve given us information and they’ve given us guidance on how to handle the information,” she said.

She agreed that most children would still have adequate immunity from their primary vaccination. “If the [booster] dose is not given at exactly 12 to 15 months of age, the child does have protection,” she said.

No contaminated vaccines have been discovered, said Merck, and the company expects to resume Hib vaccine shipments in the fourth quarter of 2008, “based on best estimates at this time.”

Some 14 million Hib vaccine doses are administered in the U.S. annually. Merck and Sanofi-Pasteur each produce about half the supply.

The CDC is working with Sanofi-Pasteur to step up production. Although it was uncertain how much additional vaccine the company could supply, the agency does not expect it to completely fill the gap.

Nevertheless, the CDC still hopes that booster shots for most children can be resumed within a few weeks.

The CDC is drawing on its stockpile of 750,000 doses, primarily to ensure that high-risk children can receive primary and booster shots. High-risk groups include American Indian children, Alaska Native children, and children with asplenia, sickle cell disease, HIV, immunodeficiencies, and certain cancers. The CDC also recommends that Hib vaccines continue to be given to individuals in close contact with patients actively infected with Hib.

No funding information or conflicts of interest were disclosed.

Additional source: Morbidity and Mortality Weekly Report

Source reference:

CDC, “Interim recommendations for the use of Haemophilus influenzae type b (Hib) conjugate vaccines related to the recall of certain lots of Hib-containing vaccines (PedvaxHIB?┬« and Comvax?┬«)” MMWR 2007; 56: 1-2.

IAC: Pregabalin Fails to Control HIV Neuropathic Pain Better than Placebo

MEXICO CITY, Aug. 8 — The anti-convulsant pregabalin (Lyrica) did better than placebo in controlling HIV-related neuropathic pain in the short term, but not over the long haul, researchers found.

Treatment with pregabalin produced a significant reduction in neuropathic pain at two weeks, reducing the NRS-Pain score by two points compared with a 1.5-point decrease in scores among placebo patients (P

Overdoing Niacin Can’t Thwart Drug Abuse Tests and Is Risky

PHILADELPHIA, April 12 — Those who try to foil urine drug tests with massive doses of niacin — it doesn’t work — may wind up in a hospital emergency department.

Life-threatening adverse reactions beyond just the typical skin flushing and itchiness included liver toxicity, acidosis, and even disrupted heart rhythms at niacin doses 100 to 500 times the 15-mg daily recommended value, said Manoj K. Mittal, M.D., of the Children’s Hospital of Philadelphia, and colleagues.

Four such cases — two adults and two teenagers — were seen in emergency departments in two years in the university health care system after trying to dodge a screen for illegal drugs, they reported online in the Annals of Emergency Medicine. What’s more, Dr. Mittal added, niacin overdosing is an exercise in futility in trying to fool the tests.

While there is no biological basis for niacin’s putative drug clearing effect, the myth may have gotten started by individuals who took the vitamin’s “flushing” and metabolism effects out of context, Dr. Mittal and colleagues said.

In an editorial that will accompany the print version of the study, Kennon Heard, M.D., and Carrie D. Mendoza, M.D., both of the Rocky Mountain Poison and Drug Center, wrote that this number of cases in a single system suggests that niacin overdosing may be fairly common to try to evade urine drug tests.

With tens of thousands of Web pages discussing this misguided use of niacin, “we expect there will be many more cases of niacin toxicity in the next few years,” Drs. Heard and Mendoza added.

“With the proliferation of urine drug testing by prospective employers and various government agencies, more patients with niacin toxicity may present to emergency departments,” Dr. Mittal and colleagues wrote.

Both adults — a 23-year-old man who abused cocaine and a 22-year-old woman who abused marijuana — took niacin before scheduled pre-employment urine drug tests. They were seen in the emergency department for niacin’s characteristic skin flushing and burning in one case and itchy erythematous rash in the other, but the reactions resolved spontaneously.

Nevertheless, “in the absence of an appropriate medical history, this reaction can be misdiagnosed as anaphylaxis or hypersensitivity reaction and treated inappropriately,” Dr. Mittal and colleagues cautioned.

The 14-year-old boy and 17-year-old girl who tried the same thing had worse consequences.

In an attempt to mask marijuana use from his parole officer, the previously healthy boy took 11 tablets of 500-mg timed-release niacin over three days. He arrived at the emergency department with nausea, vomiting, upper abdominal pain, palpitations, and dizziness.

Initially, he had hypoglycemia (26 mg/dL) that then switched to hyperglycemia when he was given dextrose (207 mg/dL). His liver function was abnormal as well with alanine aminotransferase levels that peaked on day four of hospitalization at 344 IU/L (normal range 10 to 45 IU/L) and aspartate aminotransferase levels that peaked on day three at 193 IU/L (normal range 15 to 40 IU/L). He had “impressive neutrophilia” and high-anion-gap metabolic acidosis that resulted in a misdiagnosis of diabetic ketoacidosis.

Furthermore, he had heart rhythm abnormalities. On electrocardiogram, his QT interval was 378 ms with a prolonged QT corrected interval of 511 ms, which was “probably related to the patient’s severe metabolic acidosis.”

Likewise, the girl took five 500-mg tablets of niacin over two days to clear her urine of marijuana and “ecstasy” but wound up in the hospital for nausea, vomiting, dizziness and brief unresponsiveness.

She also had high-anion-gap metabolic acidosis as well as initial hypoglycemia (70 mg/dL) that became hyperglycemia after administration of dextrose (peak 222 mg/dL). However, she did not have elevated hepatic enzymes.

Both demonstrated coagulopathy. The peak prothrombin time was 18.8 seconds for the boy and 23.1 seconds for the girl (normal range 10.3 to 12.8 seconds). The INR peaked at 1.74 on day three for the boy and 3.8 for the girl.

The “puzzling dysglycemia” was likely due to dual metabolic effects of niacin. It inhibits breakdown of stored fat, which in the setting of prolonged vomiting would have explained the initial hypoglycemia. Niacin also induces insulin resistance, so correction of hypoglycemia with dextrose “unmasked” this effect leading to hyperglycemia.

Ironically, drug screening tests turned up positive for both patients despite extreme niacin overdose, Dr. Mittal said.

While both patients improved in a few days with supportive care once niacin intake ceased, the cases suggest that healthcare providers should be aware in their differential diagnosis of misguided use of niacin among patients trying to interfere with urine drug screening, the researchers said.

“Emergency physicians should consider attempts to mask urine drug screens as a cause of unusual presentations in high-risk populations, such as military, patients on probation and with a history of drug abuse,” Drs. Heard and Mendoza wrote in their editorial.

However, “a much wider population is at risk than what is implied there,” Dr. Mittal and colleagues said, because any government job, all big employers, and those who participate in sports, among others, require urine screening.

“Health care providers should be aware of these potential adverse effects of niacin and of the misguided use of this vitamin by patients seeking to interfere with urine drug screening,” they added.

When reviewing their poison center’s records for an eight month period in 2006, Drs. Heard and Mendoza found that 15% of niacin-related were due to the use of niacin to mask drug abuse or to “purify or cleanse their system.”

In addition to these 16 callers, 12 callers reported adverse reactions under “circumstances??┬Žsuspicious for use related to masking drug screens.” Only half of all these individuals were treated in a healthcare facility.

Together, the findings “suggest that niacin toxicity while attempting to mask urine drug screens may be a growing problem,” they wrote.

The researchers reported no financial conflicts of interest.

Primary source: Annals of Emergency Medicine

Source reference:

Mittal MK, et al “Toxicity From the Use of Niacin to Beat Urine Drug Screening” Ann Emerg Med. 2007.

Additional source: Annals of Emergency Medicine

Source reference:
Heard K, Mendoza CD “Consequences Of Attempts To Mask Urine Drug Screens” Ann Emerg Med. 2007.

Caregiving Linked to Stroke Risk

The strain of caring for a disabled spouse is associated with an increased risk of stroke, researchers found.

The risk is increased for men, and especially African-American men, according to William Haley, PhD, of the University of South Florida, in Tampa, and colleagues.

On the other hand, there was no significant association of any level of caregiving stress with the risk of coronary heart disease, the researchers reported in the February issue of Stroke.

One implication of the study, the researchers wrote, is that men looking after disabled partners may need extra support.

The issue is important because about 12% of Americans older than 45 report they have what the researchers called “family caregiving responsibilities,” they noted. And high caregiver stress has been found to be a risk factor for depressive symptoms and early mortality.

To see how such stress affects cardiovascular health, the researchers turned to the so-called REGARDS study — for REasons for Geographic and Racial Differences in Stroke. It is a continuing epidemiological look at stroke and coronary heart disease incidence and mortality in a large national sample of adults over age 45.

Of the more than 30,000 participants in the study, the researchers found 767 who lived with and cared for a disabled spouse and had no history of stroke or coronary heart disease.

Based on interviews and home visits, the researchers divided the participants into those reporting high, some, or no strain associated with caregiving. They also calculated 10-year stroke and coronary heart disease risk, using Framingham risk scores.

In a multivariate regression analysis, high caregiving strain was associated with a 13.62% 10-year risk of stroke for high-strain caregivers, the researchers reported.

That was 23% higher than the estimated stroke risk of 11.06% for caregivers reporting no strain. The difference was significant at P=0.02.

But Haley and colleagues also found significant interactions between race, sex, and caregiving strains.

When those were taken into account, African-American men with high caregiving stress had an estimated 10-year stroke risk of 26.95% — markedly higher than the risk for any other race or sex group.

Among other groups with high caregiving strain, white men had a 10-year risk of about 15%, while white and African-American women had risks estimated to be between 10% and 12%.

The researchers cautioned that the study is cross-sectional, so it could be that people high in some stroke risk factors may simply find caregiving to be more stressful.

Other limitations included the fact that there were only a small number of highly stressed African-American men, which could have exaggerated the effect in this group, and the use of risk scores rather than observed stroke and cardiovascular events. The REGARDS study will have direct observation of events over time.

Interestingly, men overall in the study reported lower stress than women, perhaps because they tend to use more paid help and have more assistance from extended family, the researchers said.

It may be that the men reporting high caregiving strain lack such outside help, they said.

The study was supported by the National Institute of Neurological Disorders and Stroke.

The researchers reported no conflicts.

Blood Test Predicts Mortality Risk in Coronary Disease

VANCOUVER, British Columbia, Feb. 14 – In a sample of patients with known coronary artery disease, plasma concentrations of interleukin-6 (IL-6) and total homocysteine were the biomarkers most predictive of death, researchers here reported.

But the finding may dampen enthusiasm for the use of biomarkers in cardiovascular disease because neither proved to be a specific predictor for coronary artery disease, John S. Hill, M.D., of St. Paul’s Hospital Healthy Heart Program reported in the February issue of the Canadian Medical Association Journal.

In a cohort of 1,117 consecutive patients referred for selective coronary angiography, the investigators studied the relative utility of baseline measurements of C-reactive protein (CRP), IL-6, serum amyloid A protein, and total homocysteine as well as of lipids for predicting angiographic coronary artery disease and all-cause and coronary artery disease- related death.

The risk of death increased across quartiles for CRP, IL-6, serum amyloid A protein and total homocysteine and was most dramatic with Il-6 and homocysteine levels.

Those with the highest plasma concentrations of IL-6 had a hazard ratio of 2.57 (confidence interval [CI]: 1.62-4.09) for coronary artery disease death and all-cause mortality compared with patients with the lowest concentrations of IL-6 (P for trend= 0.001), Dr. Hill and colleagues wrote.

Likewise patients with total homocysteine in the highest quartile had a hazard ratio of 2.36 (CI: 1.53-3.65) for death compared with those with lowest concentrations of total homocysteine (P for trend < 0.001).

For IL-6, those in the highest quartile had plasma concentrations of 3.77 ng/L or more. For homocysteine, the threshold for the highest quartile was 17.4 ??mol/L or more.

The authors noted that the risk of death increased as concentrations of all biomarkers increased, but only IL-6 and total homocysteine remained independent predictors of death after adjusting for other risk factors, including age, and evidence of coronary artery disease on angiography. Age, sex, smoking, diabetes and apolipoprotein B levels but not these biomarkers were independent predictors of angiographic coronary artery disease.

Both biomarkers had “greater utility in predicting death than traditional lipid and apolipoprotein measurements,” the authors said, but they cautioned that these biomarkers do not appear to be specific predictors of coronary artery disease-related death.

Comparisons of survival between those subjects who had zero to four elevated markers among CRP, serum amyloid A protein, IL-6 and total homocysteine revealed an increasing rate of death and coronary artery disease-related death. As such, the authors suggested that the best way to use the biomarkers is to include them in a biomarker group along with CRP and serum amyloid A protein “to increase our ability to identify those subjects with the greatest risk of death.”

The study recruited 1,117 patients (797 men and 320 women) between 1993 and 1995. Angiographic results were available for 1,019.

In 2004, follow-up data were available for 1,050 patients, of whom 231 had died, including 95 who died of coronary artery disease -related causes.

In an editorial that accompanied the study, Gordon Lowe M.B., Ch.B, of the University of Glasgow wrote that the Vancouver study “adds to increasing evidence that plasma levels of inflammation biomarkers and homocysteine are more strongly related to all-cause death than to coronary artery disease; in combination with other evidence, these results do not support the hypothesis that these biomarkers play any causal roles in the pathogenesis of cardiovascular disease.”

Dr. Lowe added that these findings drive home the point that there is no need for these measurements in routine clinical practice.

Primary source: Canadian Medical Association Journal

Source reference:
Lee KWJ et al “Relative value of multiple plasma biomarkers as risk factors for coronary artery disease and death in an angiography cohort.” CMAJ 2006; 174(4): 461-6

Additional source: Canadian Medical Association Journal

Source reference:
Lowe GDO “The association between elevated levels of inflammation biomarkers and coronary artery disease and death.” CMAJ 2006; 174(4):479-80

Common Infections Linked to Increased Stroke Risk

People infected with the herpes virus, ulcer-causing bacteria, and other common bugs appear to be at increased risk of stroke from cumulative exposure to the pathogens, a new study found.
Five common infections were associated with increased stroke risk, with adjusted hazard ratios ranging from 1.13 with Helicobacter pylori (95% CI 0.68 to 1.89) to 2.19 with cytomegalovirus (95% CI 0.84 to 5.70), according to an online published Nov. 9 in the Archives of Neurology.
However, none of the individual associations was statistically significant.
The infectious burden index for the patients was associated with an increased risk of stroke of 39% per standard deviation (95% CI 1.02 to 1.90) after the researchers adjusted for demographics and risk factors.

“These results provide evidence that there is probably no single infectious agent responsible for atherosclerosis or stroke, but that a more likely mechanism for any possible association of infection with stroke is through a more general proinflammatory mechanism,” Mitchell S.V. Elkind, MD, MS, of the Neurological Institute, and colleagues wrote.

Stroke is the third leading cause of death in the U.S. and the leading cause of serious disability, but many people who suffer strokes have none of the common risk factors, such as hypertension, cardiac disease, or smoking.

As a result, researchers hope to identify other risk factors that might explain these cases. The results of previous studies have suggested that infections by herpes viruses and other pathogens might promote inflammation and thus contribute to arterial disease and stroke risk.

Elkind and colleagues obtained blood samples from 1,625 adults (average age of 68.4 years) living in northern Manhattan, none of whom had suffered a stroke, to test whether they had been infected with one or more of five common pathogens.

These included Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2. The patients were enrolled in the Northern Manhattan Study between 1993 and 2001.

“Each of these common pathogens may persist after an acute infection and thus contribute to perpetuating a state of chronic, low-level infection,” the authors wrote. “Second, prior studies demonstrated an association between each of these pathogens and cardiovascular diseases.”

The researchers followed-up with the patients annually for a median of 7.6 years, during which time 67 of the participants had strokes. The cumulative results were similar after excluding participants with coronary disease (adjusted HR 1.50; 95% CI 1.05 to 2.13) and adjusting for inflammatory biomarkers.

“Our study could have potential clinical implications,” the authors wrote. “For example, treatment and eradication of these chronic pathogens might mitigate future risk of stroke. Antibiotic therapy directed against C pneumoniae has been tested in randomized controlled trials without evidence of benefit against heart disease.

“Whether the same holds true for stroke has not yet been established. More studies will be required to further explore [infectious burden] as a potential modifiable risk factor for stroke.”

They noted that the study was limited by a lack of data on participants’ use of cholesterol-lowering drugs such as statins, preexisting inflammatory diseases, use of anti-inflammatory medications, immunosuppression status, and infection status at the time of stroke.

The study was funded by the National Institutes of Health.

The authors reported no financial conflicts of interest.

GLP-1 Agonist Wins First Incretin Showdown

In the first head-to-head comparison across new incretin drug classes in type 2 diabetes, liraglutide (Victoza) beat out sitagliptin (Januvia) for glucose control.
Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, reduced glycosylated hemoglobin by an absolute 0.60% more at the 1.8 mg dose and 0.34% more at 1.2 mg than the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (both P<0.0001), according to a report in the April 24 issue of The Lancet.
This difference in the open-label, randomized trial passed non-inferiority criteria and met superiority on both counts, reported Richard E. Pratley, MD, of the University of Vermont in Burlington, and colleagues.

The improvement would likely yield a clinically relevant advantage in microvascular complications and risk of diabetes-related mortality, they wrote.

Although potentially useful information for clinicians in choosing among the several incretin drugs now available, these results still don’t place liraglutide as the undisputed first-line agent after failure of metformin alone, cautioned an accompanying commentary.

Nearly all published randomized trials of incretin therapies have compared them with a placebo or a reference glucose-lowering agent, wrote André J. Scheen, MD, and Régis P. Radermecker, MD, both of the University of Liège in Belgium.

One exception was the LEAD 6 trial, which reported superior achievement of hemoglobin A1c goals with liraglutide versus the GLP-1 inhibitor exenatide (Byetta).

Safety and comparative efficacy over the long term during the progressive decline in beta-cell function responsible for loss of glucose control remain open questions, Scheen and Radermecker wrote.

Also, sitagliptin is a once-daily pill, which might be easier to administer than liraglutide as a once-daily injection, and is less expensive — both issues that may need to be taken into consideration on an individual basis, they noted.

“In our opinion, the range of type 2 diabetes is so heterogeneous that treatment probably needs to be tailored to individuals rather than strictly standardised,” they concluded in their commentary.

Richard Bergenstal, MD, American Diabetes Association president for medicine and science agreed.

“We’ve learned in the last several years and the last big trials that while A1c is critically important in preventing microvascular disease, you also have to look at weight gain, hypoglycemia, and quality of life,” he said in an interview with MedPage Today. “We are back to more individualizing.”

Incretin therapies have to compete with other more commonly used and less expensive options for initial add-on therapy after metformin failure — a sulfonylurea, basal insulin, or thiazolidinedione, Bergenstal said.

Pratley’s results suggest that liraglutide and sitagliptin would both be good options for patients when weight and hypoglycemia are an issue, and that liraglutide may be better for those who have farther to go to get to goal, he said.

In Pratley’s trial, both drugs resulted in weight loss over 26 weeks, although participants lost more with the 1.8 and 1.2 mg liraglutide dose than with sitagliptin (-3.38, -2.86, and -0.96 kg, respectively).

For the secondary composite endpoint of hemoglobin A1c of less than 7.0%, no hypoglycemia, and no weight gain, the same pattern was seen (46%, 37%, and 14%, respectively, P<0.0001 for both liraglutide groups versus sitagliptin).

The international trial included 665 patients ages 18 to 80 with type 2 diabetes inadequately controlled on metformin as indicated by a hemoglobin A1c of 7.5 to 10.0%.

Participants were randomized to once daily injections os liraglutide at 1.2 mg or 1.8 mg or oral sitagliptin once daily (100 mg).

After 26 weeks of treatment, results for the primary endpoint of hemoglobin A1c reduction compared with baseline were: –1.50% for 1.8 mg liraglutide (95% confidence interval –1.63 to –1.37) –1.24% for 1.2 mg liraglutide (95% CI –1.37 to –1.11) –0.90% for sitagliptin (95% CI –1.03 to –0.77)

More patients were able to get to goal on liraglutide as well.

Patients on 1.8 mg liraglutide were 4.50 times more likely (95% CI 2.90 to 6.97) and those on 1.2 mg liraglutide were 2.75 times more likely (95% CI 1.78 to 4.25) than those on sitagliptin to reach the target of a hemoglobin A1c under 7.0%.

However, liraglutide was associated with more treatment-emergent adverse events, particularly GI events.

Nausea occurred in 27% of patients on 1.8 mg liraglutide and 21% on 1.2 mg liraglutide compared with 5% on sitagliptin.

About 5% in each group reported minor hypoglycemia. There were no cases of pancreatitis.

The study was funded by Novo Nordisk.

Pratley reported that his institution has received research grants from Eli Lilly, GlaxoSmithKline, Mannkind, Merck, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, and Takeda. He reported conflicts of interest with Novo Nordisk as well as AstraZeneca, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Glenmark, Merck, Novartis, Roche, and Takeda.

Coauthors reported conflicts of interest with NovoNordisk as well as Merck Sharp & Dohme, Amylin Pharmaceuticals, Novartis, Sanofi-Aventis, Eli Lilly, Almirall, GlaxoSmithKline, International Diabetes Center, Bayer, Roche, CeQur, Lifescan, Abbott, Daiichi-Sankyo, Edwards Lifesciences, Dexcom, Mannkind, Medtronic, Merck, Quotient Diagnostics, ResMed, Takeda, Incubatin for Roche Diagnostics, Optum Health, and Bristol-Myers Squibb.

Scheen reported conflicts of interest with Novo Nordisk, Sanofi-Aventis, AstraZeneca/Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Takeda.

Radermecker reported conflicts of interest with Novo Nordisk, Novartis, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Sanofi-Aventis, and Takeda.

Scheen and Radermecker’s institution has a grant pending from Novo Nordisk, and has received fees for their consulting on national and international advisory boards.

Bergenstal reported no conflicts of interest but noted that some of the research, with which he was not involved, was carried out at his institution.