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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_352"
                     title="ICAO: Future Chronic Disease Risk Goes Beyond BMI (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18233?impressionId=1265809829297"
                     
      When it comes to predicting chronic disease, body mass index doesn&apos;t tell the whole story, according to a population-based study that found elevated risk with obesity and other metabolic risk factors independently.&lt;br&gt;
&lt;br&gt;Metabolically-healthy obese people tended toward being at least twice as likely to develop multiple metabolic risk factors and diabetes as healthy, normal weight individuals over the subsequent 3.5 years of a study led by Sarah Appleton, a postgraduate student at the University of Adelaide, Australia.&lt;br&gt;
&lt;br&gt;However, normal weight individuals with metabolic risk factors  --  a group the researchers called &quot;metabolically obese&quot;  --  were at greater risk, she told attendees at the International Congress on Abdominal Obesity in Hong Kong, a conference sponsored by the International Chair on Cardiometabolic Risk.&lt;br&gt;
&lt;br&gt;Overall, just 4.1% of the 3,743 adults in the population-based, North West Adelaide Health Study were in the normal body mass index range at baseline but had at least two of the following metabolic risk factors:&lt;ul&gt; &lt;li&gt;Triglyceride levels of 1.7 mmol/L or greater&lt;/li&gt; &lt;li&gt;HDL cholesterol under 1.0mmol/L for men or 1.3 mmol/L for women&lt;/li&gt; &lt;li&gt;Blood pressure of 130/85 mm Hg or higher&lt;/li&gt; &lt;li&gt;A fasting plasma glucose of at least 5.6mmol/L or self-reported diabetes&lt;/li&gt; &lt;li&gt;Treatment for any of these disorders &lt;/li&gt; &lt;/ul&gt;
&lt;p&gt;Although free of cardiovascular disease when they entered the study through a random population sample of the northwest region of Adelaide, after a mean of 3.5 years of follow-up, this group was 2.48 times at risk of incident cardiovascular disease or stroke events (95% CI 1.1 to 5.4).&lt;/p&gt;
&lt;p&gt;Compared with metabolically-healthy, normal weight individuals, those with metabolic risk factors tended to be&lt;strong&gt; &lt;/strong&gt;3.27 times as likely to develop diabetes (&lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Identifying these individuals for prevention efforts may require less emphasis on BMI and increased surveillance of central obesity in primary care, the researchers told the congress.&lt;/p&gt;
&lt;p&gt;&quot;The problem with BMI is it doesn&apos;t tell you where the fat is,&quot; Appleton added in an interview. &quot;Visceral fat is really bad for you.&quot;&lt;/p&gt;
&lt;p&gt;Obese individuals without multiple metabolic risk factors at baseline comprised a larger group (12.1%).&lt;/p&gt;
&lt;p&gt;They were more likely to be middle age, live in a disadvantaged neighborhood, have smoked at some point, and get less exercise than their metabolically similar, but slimmer peers.&lt;/p&gt;
&lt;p&gt;Over the subsequent 3.5 years, they were 2.82 times more likely to develop more than one metabolic risk factor than metabolically-healthy, normal weight individuals (95% CI 2.0 to 4.0).&lt;/p&gt;
&lt;p&gt;The metabolically-normal obese also tended to be 2.36 times more likely to develop diabetes (95% CI 0.8 to 7.1). On the other hand, their risk of cardiovascular disease wasn&apos;t elevated, &quot;which likely related to the younger age of that group,&quot; Appleton told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Notably, abdominal obesity as determined by a waist circumference of 80 cm and over for men or 95 cm and greater for women was 6.1 times more likely among metabolically healthy individuals if their BMI was in the obese versus normal range.&lt;/p&gt;
&lt;p&gt;But those who were in the normal BMI range were 2.2-fold more likely to be overweight or obese according to waist circumference if they had metabolic risk factors, which was statistically significant as well and likely contributed to the health risks they faced over the short-term future, Appleton said.&lt;/p&gt;
&lt;p&gt;Maintenance of metabolic health in the obese population was more likely for younger individuals (OR 2.83 for age 40 or younger, 95% CI 1.1 to 7.6) and those who were at least moderately physically active (OR 2.04, 95% CI 1.01 to 4.1).&lt;/p&gt;
&lt;p&gt;Appleton noted that these findings generally fit with data from the U.S. National Health Assessment Survey and Examination.&lt;/p&gt;
&lt;p&gt;Regardless of whether patients have abdominal obesity, BMI obesity, or other metabolic risk factors, the solution is likely similar  --  improved diet and exercise, she said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the University of Adelaide and the South Australian Department of Health.&lt;/p&gt;&lt;p&gt;Appleton reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_207"
                     title="ISET: Women Fare Better in Small Leg Vessel Procedures (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Cardiology/PeripheralArteryDisease/tb/18051?impressionId=1265809829297"
                     
      &lt;p&gt;HOLLYWOOD, Fla.  --  Contrary to expectations, women who undergo last-ditch, minimally-invasive procedures to open small blood vessels in the leg  --  and forestall amputation  --  generally have better outcomes than men, researchers reported here.&lt;/p&gt;
&lt;p&gt;Overall, 87.5% of women who underwent the infragenicular endoscopic angioplasty avoided amputation for at least two years, compared with 82.9% of the men who were similarly treated (&lt;em&gt;P&lt;/em&gt;=0.041), according to Tejas Shah, MD, of Mount Sinai Medical Center in New York City.&lt;/p&gt;
&lt;p&gt;&quot;This study is the first to compare the outcomes of men and women being treated for blocked lower-leg arteries with endovascular therapy,&quot; Shah said at the International Symposium on Endovascular Therapy (ISET). &quot;The results suggest endovascular therapy should be strongly considered in women with blocked arteries below the knee.&quot;&lt;/p&gt;
&lt;p&gt;In many endovascular procedures, women tend to do worse then men, generally because they tend to have smaller blood vessels. But in this study, involving the smallest leg blood vessels, the opposite occurred. &quot;We really don&apos;t have any good reason why there should be this gender difference,&quot; Shah said.&lt;/p&gt;
&lt;p&gt;&quot;What made this difference significant,&quot; Shah told &lt;em&gt;MedPage Today&lt;/em&gt;, &quot;was that the women in the study, overall, were at significantly greater risk of amputation than the male patients.&quot; He said that about 22.3% of men underwent treatment for claudication, compared with 12.3% of the women, but 77.7% of men were being treated for limb-threatening conditions compared with 87.7% of women.&lt;/p&gt;
&lt;p&gt;The retrospective study involved review of angioplasties, stenting, and atherectomies performed on 152 men and 125 women at Mount Sinai between July 1999 and November 2009.&lt;/p&gt;
&lt;p&gt;When adjusted for comorbidities, women treated for tibial lesions with concurrent proximal disease had higher 24-month primary patency rates compared with men.&lt;/p&gt;
&lt;p&gt;Some 46% of treated leg arteries in women remained open, compared with 30% (&lt;em&gt;P&lt;/em&gt;=0.016) in men. Shah said that a subanalysis of isolated tibial lesions indicated that 50% of women achieved 24-month primary patency rates, compared with 28.8% of men (&lt;em&gt;P&lt;/em&gt; =0.002).&lt;/p&gt;
&lt;p&gt;On the downside, women experienced higher rates of blood clots forming at the access site of the treatment (9% versus 0.6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;.0001). Clotting, typically treated with blood thinners, may require a longer stay in the hospital (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;&quot;In both men and women it is hard to keep these smaller leg blood vessels open,&quot; said Constantino Pe&amp;#241;a, MD, medical director of vascular imaging at Baptist Cardiac &amp;amp; Vascular Institute, Miami.&lt;/p&gt;
&lt;p&gt;&quot;It might be possible that women do better because of their hormone status. But we need to do prospective clinical trials to see if we can determine what factor is involved in making the procedure work better for women.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Shah listed no relevant disclosures.  Pe&amp;#241;a reported financial relationships with Bard and Medtronic.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3121"
                     title="EASD: Saxagliptin Shows Limited Benefit as Add-On (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/EASD/tb/16258?impressionId=1265809829297"
                     
      &lt;p&gt;VIENNA  --  Patients with type 2 diabetes that was inadequately controlled with metformin did better for up to two years when saxagliptin (Onglyza) was added, a researcher reported here.&lt;/p&gt;
&lt;p&gt;Even so, a majority of patients on the combination discontinued it or required a third drug because they failed to meet glycemic targets during the study, said Shoba Ravichandran, MD, of Bristol-Myers Squibb, saxagliptin&apos;s manufacturer.&lt;/p&gt;
&lt;p&gt;She reported interim results of a long-term, placebo-controlled extension of a randomized trial here at the European Association for the Study of Diabetes&apos; annual meeting.&lt;/p&gt;
&lt;p&gt;Saxagliptin, a dipeptidyl peptidase-4 inhibitor, was approved earlier this year as a treatment for type 2 diabetes.&lt;/p&gt;
&lt;p&gt;Ravichandran put a bright face on results showing relatively modest improvements from baseline in glycated hemoglobin levels, as well as missed-target rates exceeding 60% for the combination.&lt;/p&gt;
&lt;p&gt;The upside for saxagliptin: more than 80% of patients who took metformin alone had to quit the study or take rescue medication because of lack of glycemic control (&lt;em&gt;P&lt;/em&gt; not reported). Adverse events were rare in both treatment groups, Ravichandran reported.&lt;/p&gt;
&lt;p&gt;Hypoglycemic episodes were reported in 9% to 11% of patients across treatment groups, with only about one in ten of these episodes confirmed by investigators, Ravichandran said. No differences between doses or treatments were seen for any individual type of adverse event.&lt;/p&gt;
&lt;p&gt;At week 102, she added, between 24% to 33% of patients taking the combination had HbA1c levels below 7.0%, compared with 12% taking metformin alone (&lt;em&gt;P&lt;/em&gt; not reported).&lt;/p&gt;
&lt;p&gt;&quot;Saxagliptin plus metformin provided sustained, clinically meaningful effects on glycemic control [through] week 102 when compared to placebo plus metformin,&quot; she told attendees here.&lt;/p&gt;
&lt;p&gt;But her assessment was challenged by Geremia Bolli, MD, of the University of Perugia in Italy.&lt;/p&gt;
&lt;p&gt;He suggested the mean improvement from baseline in the saxagliptin-metformin patients  --  about 0.6% to 0.7% in HbA1c levels, depending on the saxagliptin dose  --  left many patients inadequately treated.&lt;/p&gt;
&lt;p&gt;Because baseline levels were just above 8.1%, Bolli said, &quot;most of the patients were really not at the target of 7.0% despite the higher dose of saxagliptin.&quot;&lt;/p&gt;
&lt;p&gt;Ravichandran agreed, but argued that such a result was not surprising, given the patients&apos; history.&lt;/p&gt;
&lt;p&gt;The study has been following 743 participants who started in a 24-week, randomized, placebo-controlled, four-arm trial and then stayed on their assigned medications for up to 42 additional months.&lt;/p&gt;
&lt;p&gt;Ravichandran provided results from a January 2008 &quot;data lock&quot; on the trial, when patients had been treated for a total of up to 102 weeks.&lt;/p&gt;
&lt;p&gt;Three doses of saxagliptin were tested in the study: 2.5, 5, and 10 mg once daily, along with metformin at doses of 1,500 to 2,500 mg/day. Metformin was maintained at doses patients were taking at study entry.&lt;/p&gt;
&lt;p&gt;All patients had HbA1c levels of at least 7.0% at study baseline (mean 8.0% to 8.1%), despite at least eight weeks of metformin treatment, and were overweight to obese (mean BMI 32).&lt;/p&gt;
&lt;p&gt;During the extension, patients failing to meet increasingly stringent HbA1c targets  --  starting with 8.0% and lowered to 7.5% and then 7.0% through about 20 months  --  were encouraged to take pioglitazone (Actos) as rescue medication or leave the trial to pursue other treatments.&lt;/p&gt;
&lt;p&gt;Some of the efficacy data showed better results with the higher saxagliptin doses.&lt;/p&gt;
&lt;p&gt;For example, the greatest percentage of patients meeting the 7.0% target for HbA1c at week 102 was seen in the 10-mg group (33%, versus 30% for 5 mg and 24% for 2.5 mg).&lt;/p&gt;
&lt;p&gt;But the opposite pattern was seen for two-hour postprandial blood glucose levels, with a 40% decrease from baseline at week 102 occurring with the 2.5-mg dose and a 23% reduction seen with 10 mg. The metformin-placebo had a mean reduction of 4% in postprandial glucose (&lt;em&gt;P&lt;/em&gt; not reported).&lt;/p&gt;
&lt;p&gt;Ravichandran said it was not surprising that most patients failed to achieve 7.0% HbA1c.&lt;/p&gt;
&lt;p&gt;&quot;A fair number of subjects were not in target, but that&apos;s something one would expect&quot; in a two-year study, she said, pointing out that participants had established, poorly controlled disease to start with. &quot;They had some amount of beta cell failure already,&quot; she said.&lt;/p&gt;
&lt;p&gt;Bolli also criticized the investigators&apos; decision to maintain metformin doses at baseline levels throughout the study.&lt;/p&gt;
&lt;p&gt;&quot;I think one should try to maximize the metformin dose in everybody,&quot; he said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by Bristol-Myers Squibb.&lt;/p&gt;&lt;p&gt;Ravichandran is an employee of Bristol-Myers Squibb.&lt;/p&gt;&lt;p&gt;Other investigators on the study reported relationships with Amylin, Eli Lilly, Johnson &amp;amp; Johnson, Novartis, Pfizer, Roche, Takeda, Merck, Novo Nordisk, Metabasis, sanofi-aventis, and AstraZeneca.&lt;/p&gt;&lt;p&gt;Bolli has had relationships with sanofi-aventis, Mannkind, Novartis, and Eli Lilly.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3126"
                     title="EASD: Phase III Data Look Good for Novel Diabetes Drug (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/EASD/tb/16270?impressionId=1265809829297"
                     
      &lt;p&gt;VIENNA  --  An investigational drug targeting an insulin-independent pathway in type 2 diabetes produced early and substantial reductions in blood glucose and body weight in a phase III study, a researcher said here.&lt;/p&gt;
&lt;p&gt;After 24 weeks of treatment, glycated hemoglobin levels declined from 0.7% to 0.8% with dapagliflozin, an inhibitor of renal sodium-glucose co-transporter 2 (SGLT2). That compared to a decline of 0.3% among patients in a placebo group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05), according to Cliff Bailey, PhD, of Aston University in Birmingham, U.K.&lt;/p&gt;
&lt;p&gt;Patients receiving the drug also lost 3 to 4 kg of body weight, as opposed to less than 2 kg with placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05), Baily reported at the European Association for the Study of Diabetes&apos; annual meeting here.&lt;/p&gt;
&lt;p&gt;SGLT2 is a key molecule in the reabsorption of glucose in the kidneys, where it is put back into circulation, Bailey explained. Inhibiting it forces the kidneys instead to put glucose into urine where it is excreted, thereby lowering blood glucose.&lt;/p&gt;
&lt;p&gt;Dapagliflozin was the first SGLT2 inhibitor to reach clinical testing, and is now the first for which phase III data have been reported. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/6047&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/6047&quot; target=&quot;_blank&quot;&gt;ADA: Investigational Diabetes Drug Rids Glucose Via Urine&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;In the current trial, 546 patients with type 2 diabetes poorly controlled with metformin were randomized to three doses of dapagliflozin (2.5, 5 or 10 mg once daily) or placebo in addition to their previous doses of metformin.&lt;/p&gt;
&lt;p&gt;Mean HbA1c levels at baseline were 8.1% and mean metformin doses ranged from about 1,800 to 1,900 mg/day in the four groups.&lt;/p&gt;
&lt;p&gt;About one-quarter of each dapagliflozin group had at least a 5% decrease in body weight, compared with 6% of the placebo group who lost that much, Bailey said. However, corresponding data on the proportion of patients meeting HbA1c targets were not available.&lt;/p&gt;
&lt;p&gt;Bailey did report on a variety of other outcomes, all expressed as mean change from baseline: &lt;ul&gt; &lt;li&gt;Diastolic blood pressure: -2.1 to -5.1 mm Hg for dapagliflozin, -0.1 mm Hg for placebo (&lt;em&gt;P&lt;/em&gt; not reported)&lt;/li&gt; &lt;li&gt;Fasting plasma glucose: -17.8 to -23.5 mg/dL for dapagliflozin, -6.0 mg/dL for placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05)&lt;/li&gt; &lt;li&gt;Hematocrit: 0.98% to 1.65% increase for dapagliflozin, -1.14% for placebo (&lt;em&gt;P&lt;/em&gt; not reported)&lt;/li&gt; &lt;li&gt;Uric acid: -0.53 to -0.82 mg/dL for dapagliflozin, -0.04 mg/dL for placebo (&lt;em&gt;P&lt;/em&gt; not reported)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Bailey said orthostatic hypotension was not increased with the drug, despite the decreases in blood pressure. Nor were there any differences between the dapagliflozin groups and placebo in the incidence of hypoglycemic episodes.&lt;/p&gt;
&lt;p&gt;Serious adverse events were rare, and only 17 patients in the study, distributed evenly across treatment groups, discontinued because of adverse events.&lt;/p&gt;
&lt;p&gt;Some increase was seen in female genital infections, with up to 13% of patients taking dapagliflozin affected, compared with 5% of the placebo group. Bailey said this potential side effect was not a focus of the study, but said it was a concern that would be followed in future trials.&lt;/p&gt;
&lt;p&gt;Session co-chair Hannele Yki-J&amp;#228;rvinen, MD, of the University of Helsinki in Finland, said dapagliflozin appeared promising on the basis of these data, but some questions remain.&lt;/p&gt;
&lt;p&gt;&quot;It looks wonderful, glucose goes down, blood pressure goes down,&quot; she said. But, she added, &quot;I wonder if this degree of decrease in glucose levels actually improves insulin action and insulin secretion. Those are the type of things we would like to influence with the drug.&quot;&lt;/p&gt;
&lt;p&gt;John Buse, MD, of the University of North Carolina in Chapel Hill, commented that the HbA1c reduction was relatively modest  --  about the same as drugs such as sitagliptin (Januvia) and less than some other drug classes, he said.&lt;/p&gt;
&lt;p&gt;Nevertheless, he said the weight loss and lack of other major adverse effects were in dapagliflozin&apos;s favor. If it&apos;s &quot;a drug you can give to everybody&quot; with even modest efficacy, it would find a place, he suggested.&lt;/p&gt;
&lt;p&gt;Other phase III trials of the drug are under way, according to its manufacturers, Bristol-Myers Squibb and AstraZeneca.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by Bristol-Myers Squibb and AstraZeneca.&lt;/p&gt;&lt;p&gt;Bailey reported no additional potential conflicts of interest.&lt;/p&gt;&lt;p&gt;Several study co-authors were Bristol-Myers Squibb employees.&lt;/p&gt;&lt;p&gt;Yki-J&amp;#228;rvinen reported no potential conflicts of interest.&lt;/p&gt;&lt;p&gt;Buse had relationships with Insulet and Novo Nordisk.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3166"
                     title="EASD: New Drug Classes Entering Type 2 Pipeline"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/EASD/tb/16316?impressionId=1265809829297"
                     
      &lt;p&gt;VIENNA  --  Farnesoid X receptor agonists, 11-&amp;#946;-HSD1 inhibitors, and glucokinase activators are some of the new approaches to treating type 2 diabetes described in research presented here, but some senior researchers expressed doubts about the clinical need for them.&lt;/p&gt;
&lt;p&gt;Early-stage clinical data were reported at the European Association for the Study of Diabetes annual meeting.&lt;/p&gt;
&lt;p&gt;For example, Reid Huber, PhD, of Incyte Corp., said that glycated hemoglobin levels dropped about 0.5% after 12 weeks of treatment with an 11-&amp;#946;-HSD1 inhibitor called INCB13739 in a placebo-controlled, 159-patient phase II trial.&lt;/p&gt;
&lt;p&gt;Insulin resistance, as measured by the HOMA-IR scale, was reduced by a full point at the highest dosage of the drug, whereas it increased 0.25 points in the placebo group.&lt;/p&gt;
&lt;p&gt;Blood lipid levels  --  particularly low-density lipoprotein cholesterol  --  also declined by a clinically significant degree, Huber said.&lt;/p&gt;
&lt;p&gt;The 11-&amp;#946;-HSD1 target is an enzyme that catalyzes the conversion of cortisone to cortisol in vivo. Huber explained that that attracted drug-development interest in type 2 diabetes because of evidence that it is upregulated in obese patients and those with insulin resistance.&lt;/p&gt;
&lt;p&gt;Also, Cushing syndrome, which results from defective cortisol metabolism, shares features with type 2 diabetes, including insulin insensitivity, obesity, and hypertension.&lt;/p&gt;
&lt;p&gt;Clinical results for a drug with a very different target were also presented here.&lt;/p&gt;
&lt;p&gt;David Shapiro, MD, of Intercept Pharmaceuticals, said an agent that activates farnesoid X receptors showed promising signs of activity in patients with type 2 diabetes and nonacloholic fatty liver disease (NAFLD) in a brief, placebo-controlled pilot study.&lt;/p&gt;
&lt;p&gt;Farnesoid X intracellular receptors regulate lipid metabolism and also appear to control insulin sensitivity and body fat mass, Shapiro said.&lt;/p&gt;
&lt;p&gt;The company&apos;s drug, INT-747, is an analogue of the receptors&apos; natural ligand, chenodeoxycholic acid.&lt;/p&gt;
&lt;p&gt;Two doses were tested against placebo in 64 patients in a six-week, double-blind trial. Duration was too short to use HbA1c as an endpoint, so Shapiro and colleagues instead measured glucose disposal rates under euglycemic clamp conditions.&lt;/p&gt;
&lt;p&gt;Both with low- and high-dose insulin, glucose disposal rates increased from baseline to the end of treatment, whereas they declined in patients receiving placebo.&lt;/p&gt;
&lt;p&gt;Patients taking a 25-mg daily dose of INT-747 had a mean 1% loss of body weight, while a 50-mg dose was associated with a 2% loss, Shapiro reported. No change was seen in the placebo group (not significant).&lt;/p&gt;
&lt;p&gt;Adverse events that appeared more common with the drug included constipation and headache.&lt;/p&gt;
&lt;p&gt;Both Huber and Shapiro said their drugs were slated for more clinical testing.&lt;/p&gt;
&lt;p&gt;Data on two glucokinase activators were presented as well.&lt;/p&gt;
&lt;p&gt;Glucokinase is a glucose-sensing enzyme that is critical in the homeostatic system by which insulin secretion is matched to blood glucose levels. Activating this pathway is expected to lead to increased insulin secretion whenever blood glucose is elevated, such as after meals.&lt;/p&gt;
&lt;p&gt;Agents developed by Merck and Array BioPharma were described in separate poster presentations.&lt;/p&gt;
&lt;p&gt;Elizabeth Migoya, PharmD, of Merck, reported that a glucokinase activator called MK-0599 reduced plasma glucose levels relative to placebo in healthy, nondiabetic volunteers.&lt;/p&gt;
&lt;p&gt;Similar phase I results were also reported for the Array product, ARRY-403, except that its study involved patients with type 2 diabetes.&lt;/p&gt;
&lt;p&gt;James Trevillyan, PhD, said that daytime glucose concentrations, both postprandial and at other times, were reduced following administration of the drug after acute dosing. Fasting plasma glucose levels were reduced as well, compared with placebo.&lt;/p&gt;
&lt;p&gt;Insulin and C-peptide levels were increased &quot;consistent with the mechanism of action,&quot; Trevillyan reported.&lt;/p&gt;
&lt;p&gt;But Edwin Gale, MD, of the University of Bristol in U.K. and editor of the EASD&apos;s official journal, &lt;em&gt;Diabetologia&lt;/em&gt;, suggested the difficulties in managing patients with type 2 diabetes were unlikely to be solved with new drugs.&lt;/p&gt;
&lt;p&gt;&quot;I&apos;m not interested in new drug classes,&quot; he said. &quot;We need to get on top of the ones we have.&quot;&lt;/p&gt;
&lt;p&gt;John Buse, MD, of the University of North Carolina, said that safety had become the paramount issue in diabetes therapy.&lt;/p&gt;
&lt;p&gt;More important than improving the potential for reducing blood glucose, he suggested, is ensuring that therapy doesn&apos;t increase patients&apos; overall risk for adverse effects, including hypoglycemia as well as cardiovascular events.&lt;/p&gt;
&lt;p&gt;Buse said the FDA had been appropriately cautious in reviewing the most recent new class of diabetes drugs, the dipeptidyl peptidase-4 inhibitors.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The studies were funded by the drugs&apos; manufacturers: Incyte, Intercept Pharmaceuticals, Array BioPharma, and Merck.&lt;/p&gt;&lt;p&gt;The presenters were employees of the respective manufacturers.&lt;/p&gt;&lt;p&gt;Gale reported no potential conflicts of interest.&lt;/p&gt;&lt;p&gt;Buse had relationships with Insulet and Novo Nordisk.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>