Januvia Linked To Increase in Heart Failure Hospitalizations Reply

The cardiovascular effects of drugs used for glucose control in patients with diabetes have been a subject of controversy for many years now. More recently, attention has started to focus specifically on the risk for heart failure. Now, an observational study will likely raise new questions about the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin (Januvia, Merck).

In a paper published in JACC Heart Failure, Daniala Weir and colleagues analyzed insurance claims from a database of more than 7600 patients with diabetes and heart failure.

Click here to read the full post on Forbes.

 

 

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Major Medical Organizations Establish Ambitious Diabetes Registry Reply

Our knowledge of diabetes today is a bit like the way blind men understand an elephant. With a myriad of isolated perspectives it’s nearly impossible to gain a broad overview. Now, a new initiative from a group of major medical organization will seek to provide the tools to better see a full picture of the elephantine problem of diabetes.

The American College of Cardiology, the American Diabetes Association, the American College of Physicians, and the Joslin Diabetes Center announced today that they will launch the Diabetes Collaborative Registry, which they say is “aimed at tracking and improving the quality of diabetes and cardiometabolic care across the primary and specialty care continuum.”

Click here to read the full post on Forbes.

Blind_monks_examining_an_elephant

 

 

Intensive Insulin Therapy Saves Lives– But Is The Finding Still Relevant? 1

A trial that started back in 1990 continues to demonstrate a significant mortality advantage for intensive insulin therapy in heart attack (MI) patients. But experts say the trial design is so outdated that the findings should have no influence on clinical practice today.

During the years 1990 through 1993 the Swedish DIGAMI I (Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infaction 1) trial randomized 620 MI patients with elevated glucose levels to either intensive insulin treatment or conventional therapy. Earlier results from the trial showed beneficial effects, including improved survival, for patients in the intensive treatment arm.

Now, a paper published in The Lancet Diabetes & Endocrinology, presents 20-year followup results showing an average 2.3 year increase in survival for patients in the treatment arm (median survival 7.0 years versus 4.7 years, HR 0.83, CI 0.70-0.98, p=0.27).

Click here to read the entire post on Forbes, including an extensive comment from Darren McGuire.

 

Glucose Measurements Don’t Improve Cardiovascular Risk Assessment Reply

Although blood glucose and glycated hemoglobin (HbA1c) play a central role in diabetes, the value of these measurements to assess cardiovascular risk has been unclear. Now, in a paper published in JAMA, members of the Emerging Risk Factors Collaboration analyze data from nearly 300,000 people without known diabetes or cardiovascular disease who were enrolled in 73 prospective studies.

Click here to read the full post on Forbes.

 

 

Heart Failure: The Missing 800 Pound Gorilla In Diabetes Trials Reply

Is heart failure the missing 800 pound gorilla in diabetes trials? That’s the argument proposed by a group of  prominent cardiovascular and diabetes researchers.

It was long believed that by virtue of their glucose-lowering properties diabetes drugs would confer substantial cardiovascular benefits. Now, however, that belief is no longer widely held and the FDA now requires cardiovascular outcome trials for new diabetes drugs. But, write the researchers in  an article published in The Lancet Diabetes & Endocrinology, these trials are failing to track and analyze one key cardiovascular endpoint, thereby diminishing the value of these trials in assessing the cardiovascular effects of diabetes drugs.

Click here to read the full post on Forbes.

 

FDA Investigating Heart Failure Risk Linked To Onglyza Reply

The FDA said today that it was conducting an investigation of a possible increased risk for heart failure associated with the diabetes drug saxagliptin. Saxagliptin is marketed by AstraZeneca as Onglyza and Kombiglyze XR. (AstraZeneca recently completed the purchase of all rights to the drug from its manufacturer, BristolMyers-Squibb.)

The investigation stems from findings from the cardiovascular outcomes trial SAVOR-TIMI 53 trial  in which more than 16,000 type 2 diabetics were randomized to the DPP-4 inhibitor saxagliptin or placebo.

Click here to read the full post on Forbes.

 

 

 

 

Mediterranean Diet Protects Against Diabetes, Regardless of Weight Loss Reply

Even if it doesn’t lead to weight loss, a Mediterranean diet could help prevent the onset of type 2 diabetes, according to a subanalysis of last year’s influential PREDIMED study. In the main trial, reported in the New England Journal of Medicine, nearly 7500 people at high risk for cardiovascular disease were randomized to a low-fat diet or a Mediterranean diet supplemented by either extra-virgin olive oil (EVOO) or nuts. After nearly 5 years’ follow-up, the study was stopped early because of a significant reduction in cardiovascular events in the Mediterranean diet groups.

The new paper, published in the Annals of Internal Medicineexamines the development of diabetes — a prespecified secondary outcome — among the 3541 participants who did not have diabetes at baseline and for whom the follow-up diabetes status was available. After 4.1 years’ follow-up, there was a significant 30% reduction in the risk for diabetes in the combined Mediterranean diet groups compared with the low-fat diet group (HR 0.70,  CI 0.54 – 0.92)….

Click here to read the full story on Forbes.

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Cardiology Goes Better With Coke 3

Diet Coke - get cancer, not fat

At the bottom of this post I’ve reprinted an email cardiologists are receiving from the American College of Cardiology. See the bottom of the message for the disclosure that Coca Cola is paying for this educational program. I don’t have much to say about this though I wonder what the faculty of this program will say about the role of sugared soda and obesity. I also wonder what position the ACC will take on public health efforts to curb sugar consumption.

There’s no reason to be surprised about this. Last year the president of the ACC was one of 22 participants chosen by the Coca-Cola Company to carry the Olympic Flame. And the ACC is far from the only mainstream medical organization to take money from Big Sugar. Coke pays a lot of money to the National Heart Lung and Blood Institute to put a red dress logo on the Diet Coke label and the American Heart Association has struck deals with, among others, Cheetos and Subway.

See Yoni Freedhoff’s Weighty Matters blog for much more about Coca Cola’s efforts to influence medical organizations.

Here’s the ACC email:

The American College of Cardiology is teaming up with the Preventive Cardiovascular Nurses Association (PCNA) to offer Never Too Early, Never Too Late: Cardiovascular Health for Women Throughout the Lifespan, an educational webinar, on Wednesday, August 14th from 1:00 p.m. – 2:00 p.m. EDT. This complimentary webinaroffers a comprehensive view of women’s cardiovascular health as they age. Our expert faculty, Jo-Ann Eastwood, PhD, RN, CCNS, ANCP-BC and Martha Gulati, MD, MS, FACC, will provide perspectives on clinical encounters during the childbearing years, perimenopausal period and in later life, while presenting opportunities to focus on, when indicated, cardiovascular disease (CVD) risk reduction, and the session will be moderated by JoAnne Foody, MD, FACC. During this webinar, the educators will encourage clinicians to seek and seize opportunities to discuss optimal cardiovascular management with their women patients in clinical practice settings, and as equally important, to champion them with their colleagues in the primary care and women’s health fields.Webinar highlights include:

  • A look at how gestational diabetes, pregnancy-associated hypertension and preeclampsia predict future CVD risk
  • Exploration into the prevalence of hypertension in women vs. men throughout the lifespan
  • Why gender differences matter with regard to tobacco use and cessation
  • The impact of women’s physical activity level on cardiovascular risk
  • Examples of successful cardiovascular health improvement programs targeted to women in a variety of age cohorts
  • One hour of CME, CNE and RD credit

Click here for additional registration, accreditation and faculty information for this complimentary educational course, Never Too Early, Never Too Late: Cardiovascular Health for Women Throughout the Lifespan. We hope you will join us on August 14th from 1:00 p.m. – 2:00 p.m. EDT!

This course is being presented by the American College of Cardiology and the Preventive Cardiovascular Nurses Association (PCNA) through an educational grant from

With One Big Exception FDA Reviewers Back More Benign View Of Avandia Trial Reply

 

The FDA today released a 538-page briefing document for an advisory panel meeting on Wednesday and Thursday that will reassess a key clinical trial and reconsider the fate of the now-tarnished former blockbuster diabetes drug rosiglitazone (Avandia, GlaxoSmithKline). (Click here for the FDA documents.) As reported last week, the re-adjudication of the RECORD safety trial performed by the Duke Clinical Research Institute (DCRI) confirmed the initial finding of the trial that rosiglitazone was not associated with an increased risk for cardiovascular events.

 

For the most part, the FDA documents released today express strong support for the DCRI re-adjudication. But one FDA official, Thomas Marciniak, remains highly critical of RECORD  and says the trial data and, therefore, the analysis of the data from GSK and DCRI are completely unreliable. All parties agree, however, that the fundamental underlying design flaws of RECORD–  in particular, it’s open-label design– mean that data from the trial will never provide definitive assurance about the safety of rosiglitazone.

 

One FDA reviewer said the DCRI review of the mortality results in RECORD was “well-conceived and comprehensive” and “no stone was left unturned.” But the same reviewer states:

 

There is no amount of analytical rigor that can compensate for a weak trial design that is exacerbated by elements of poor execution, both of which afflicted RECORD. Its open- label non-inferiority design was simply problematic, especially for ascertainment of non-mortality MACE during trial execution…. Thus, while we agree with the analytical findings of the DCRI mortality re-analysis, we would emphasize that RECORD’s design irreparably hampers its ability to characterize definitively the CV risk of rosiglitazone.

 

The panel may well accept the findings of the re-adjudication and the FDA analysis. In that case the terrifying specter looming over the FDA and the rest of the medical establishment– that not just rosiglitazone but the entire drug development and approval process was fundamentally flawed and unreliable– will be put to rest, at least for now.

 

A Bitter Feud

 

Buried in the massive document is a bitter feud between an FDA rebel, Thomas Marciniak, and his bosses and other senior officials in the FDA’s drug division….

Click here to read the full story on Forbes.

 

Fda

 

FDA Schedules Another 2 Day Avandia Advisory Panel Reply

Once again the controversial diabetes drug rosiglitazone (Avandia, GlaxoSmithKline) will be the subject of a 2 day FDA hearing. According to a meeting announcement scheduled to be published in the Federal Register on Monday, the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee will meet on June 5 and June 6 to  “discuss the results of an independent readjudication of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial.”

Click here to read the full story on Forbes.

 

Recording vinyl to CD

 

Partial Rosiglitazone/RECORD Chronology

Cuban History Offers Important Lessons For Global Health Today 1

A large new study from Cuba shows the impressive benefits that can be achieved with weight loss and increased exercise. Much more ominously, the same study shows the dangers associated with weight gain and less exercise.

In the study, published in BMJ, researchers took advantage of a “natural” experiment that occurred in Cuba as a result of a major economic crisis in the early 1990s. Relying on 30 years of superb health statistics available in the country, the researchers analyzed the dramatic health effects associated with the economic crisis, which last from 1991 through 1995, and the subsequent recovery.

During the economic crisis caloric intake decreased and physical activity increased, resulting in a 5.5 kg reduction in weight and a very high (80%) proportion of the population classified as physically active…

Click here to read the full story on Forbes.

 

 

English: A man fixing the tire of a "Bici...

 

 

Amid Rising Tide Of Diabetes More Patients Reach Treatment Goals Reply

There’s a glimmer of good news amidst all the recent bad news about diabetes. Although the prevalence of diabetes has doubled over the last generation, more people today  are reaching their treatment goals than in the past. New data from the National Health and Nutrition Examination Surveys (NHANES), published online today in Diabetes Care, show that efforts to control hemoglobin A1C, blood pressure, and LDL cholesterol in patients diagnosed with diabetes have achieved some success, but they also demonstrate that there’s enormous room for improvement.

Click here to read the full post on Forbes.

العربية: جهاز قياس غلوكوز الدم. Česky: Glukome...

CABG Highly Cost Effective In Diabetics With Multivessel Disease Reply

In November the main results of the FREEDOM trial showed that diabetics with multivessel disease do better with CABG than PCI. Now the findings of the trial’s cost-effectiveness study, published online in Circulation, demonstrate that CABG is also highly cost-effective when compared with PCI.

Elizabeth Magnuson and colleagues  found that although CABG initially cost nearly $9,000 more than PCI ($34,467 versus $25,845), over the long term it was more cost effective. At five years, greater follow-up costs in the PCI group, in large part due to a greater number of  repeat revascularization procedures, reduced the difference so that CABG cost only $3,600 more than PCI. The researchers calculated that CABG had a lifetime cost-effectiveness of $8,132 per QALY (quality-adjusted life-year) gained, which is considered highly cost effective. The finding was consistent across a broad range of assumptions.

The authors concluded “that CABG provides not only better long-term clinical outcomes than DES-PCI but that these benefits are achieved at an overall cost that represents an attractive use of societal health care resources. These findings suggest that existing guidelines that recommend CABG for diabetic patients with multivessel CAD remain appropriate in current practice and may provide additional support for strengthening those recommendations.”

“With great concerns about escalating healthcare costs, it’s very important when setting policy to understand the benefits gained from additional expenditures over the long run,” said Magnuson, in an AHA press release. “This is especially true in cardiovascular disease where many interventions tend to be very costly up front.”

 

FREEDOM Lends Strong Support To CABG For Diabetics With Multivessel Disease 3

Editor’s note: The embargo on FREEDOM was lifted early after a press release was published by mistake.)

Diabetics with multivessel disease do better with CABG than PCI, according to FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease), a large NIH-sponsored study presented at the American Heart Assocation in Los Angeles and published simultaneously in the New England Journal of Medicine.

The study was designed to evaluate the  relative worth of the two revascularization procedures in diabetics with multivessel disease. Although many studies, including BARI, ARTS, CARDia, and SYNTAX, suggested that CABG was more effective than PCI in this population, PCI has remained a popular procedure in this group. Now, many experts agreed here in Los Angeles, FREEDOM may well dampen enthusiasm for PCI in this group.

In the trial, 1900 patients were randomized to either PCI with a drug-eluting stent or CABG. After followup for at least two years the primary outcome– the composite of death, nonfatal MI, or nonfatal stroke– occurred more often in the PCI group. There were more deaths and MIs in the PCI group but more strokes in the CABG group:

Here are the 5-year event rates:

Composite endpoint: 26.6% in the PCI group versus 18.7% in the CABG group (p=0.005)

  • Deaths: (16.3% versus 10.9%, p=0.049) but more strokes in the CABG group
  • MI: 13.9% versus 6%, p<0.001)
  • Stroke: 2.4% versus 5.2%, (p=0.03)

The results in favor of CABG were consistent across all the prespecified subgroups, including severity of disease as assessed by the SYNTAX score.

In an accompanying editorial, Mark Hltaky discussed the resistance of many cardiologists to accepting that CABG is superior to PCI in this patient population. Previous studies were dismissed because they were outdated, an argument that Hlatky labels “a catch-22, since long-term studies are needed to compare hard outcomes, but evidence from long-term studies may be ignored if therapies are evolving.” In particular, PCI advocates  have proposed that the use of drug-eluting stents would close the gap between PCI and CABG.

Now, he writes, 17 years after the NHLBI issued a clinical alert based on the results of the BARI trial, FREEDOM “provides compelling evidence of the comparative effectivesness of CABG versus PCI.”

He concludes:

“The results of the FREEDOM trial suggest that patients with diabetes ought to be informed about the potential survival benefit from CABG for the treatment of multivessel disease. These discussions should begin before coronary angiography in order to provide enough time for the patient to digest the information, discuss it with family members and members of the heart team, and come to an informed decision.”

At an AHA press conference, David O. Williams said that FREEDOM “provides meaningful information to help” cardiologists choose the best therapy for their patients and that it will cause “a definite change in practice.”

At the same press conference, Alice Jacobs said that FREEDOM might result in CABG receiving a class 1 recommendation in the guidelines. Now, she said, “one would think long and hard” about offering PCI to diabetics with multivessel disease.

Mandatory YouTube Link for this trial:

Click here to read the AHA press release…

ALTITUDE Autopsy Shows What Went Wrong With Aliskiren Reply

In its short lifespan the direct renin inhibitor aliskiren (a.k.a., Rasilez or Tekturna) rapidly declined from being a highly promising, first-of-its kind drug to a major failure. The death blow was struck last December with the early termination of the ALTITUDE trial, after the data and safety monitoring committee found an increased risk in patients taking aliskiren. Now the final results of the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints have been presented at Kidney Week 2012 in San Diego and simultaneously published in the New England Journal of Medicine.

8,561 type 2 diabetics at high risk for cardiovascular and renal complications already receiving an ACE inhibitor or an angiotensin-receptor blocker were randomized to receive aliskiren or placebo. The primary outcome of a cardiorenal event (CV death, resuscitated death, MI, stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease or doubling of baseline creatinine) occurred more often in the aliskiren group, although this difference did not achieve statistical significance:

  • 18.3% for aliskiren versus 17.1% for placebo (hazard ratio, 1.08; 95% CI, 0.98-1.20; P=0.12).

A similar trend was observed for just cardiovascular outcomes:

  • 13.8% versus 12.6%, respectively (hazard ratio, 1.11; 95% CI, 0.99-1.25; P=0.09)

Compared with placebo, patients on aliskiren had lower blood pressure and a greater reduction in the urinary albumin-to-cretinine ratio. But there was also a significantly higher risk of hyperkalemia (39.1% versus 29.9%; P<0.001) and hypotension (12.1% versus 6.3%, p<0.001).

The authors concluded that the addition of aliskiren to standard therapy in high risk type 2 diabetics “is not supported by these data and may even be harmful.” The result of ALTITUDE, they write, “underscores the need to go beyond surrogate biomarkers and obtain risk-benefit data from clinical end-point trials to better inform clinical decisions.”

UK Study Casts Doubts On Value Of Type 2 Diabetes Screening Reply

The dramatic growth in type 2 diabetes has resulted in increased interest in screening programs. Now a new study published in the Lancet raises concerns that screening programs may not result in long-term improvement in outcomes.

In the ADDITION-Cambridge study, investigators in the UK randomized general practices to either screening or no screening.  The practices allocated to screening were further divided to either intensive cardiovascular risk reduction or standard care. The study population included more than 20,000 adults 40-69 years of age at high risk for undiagnosed diabetes.

3% of patients in the screening groups received a diagnosis of diabetes. After a median followup of 9.6 years, there were no significant differences between the screened population and the control group.

Rate per 1,000 person-years and hazard ratios for the no-screening and the screening group:

  • Mortality: 9.89 versus 10.50, 1.06 (CI 0.90-1.25)
  • CV mortality: 3.25 versus 3.30, 1.02 (0.75-1.38)

The authors proposed several explanations for the lack of benefit associated withs screening, including ad-hoc screening outside the practice setting in the unscreened group, patients who did not follow the screening program, and concurrent gains in identifying and managing other cardiovascular risk factors during the study period. In addition, the patient population in the study may have been a relatively healthy population with a lower prevalence of undiagnosed diabetes.

The authors concluded that “if population-based screening for diabetes is to be implemented, it should be undertaken alongside assessment and management of risk factors for diabetes and cardiovascular disease and population level preventive strategies targeting underlying determinants of these diseases.”

In a Lancet press release, senior author Simon Griffin said that “the benefits of screening might be smaller than expected and restricted to individuals with detectable disease.  However, benefits to the population could be increased by including the detection and management of cardiovascular risk factors alongside the assessment of diabetes risk, performing repeated rounds of screening, and improving strategies to maximize the uptake of screening.”

In an accompanying comment, Michael Engelgau and Edward W Gregg write that prevention programs should screen not just for diabetes but for high-risk individuals as well, though they note that this strategy “assumes that effective prevention programs are available to high-risk cases.” Further, the value of screening depends “on more than just mortality as an outcome,” and will need to include morbidity, quality of life, and costs.
Click here to read the Lancet press release…

A Manhattan Project To End The Obesity Epidemic 3

A newly launched nonprofit organization, the Nutrition Science Initiative, will try to find an answer to the question,  “What should we eat to be healthy?” NuSI is nothing if not ambitious: its goal is to seek “the end of fad diets and high obesity rates.”

The founders of the organization, called NuSI (pronounced “new see”) for short, are Gary Taubes and Peter Attia. Taubes is the science journalist who helped launch the low-carb diet resurgence with his controversial New York Times magazine articles and subsequent books, Good Calories, Bad Calories and Why We Get Fat. Attia, who is the President of NuSI, trained in surgery at Johns Hopkins and the NIH before working as a consultant at McKinsey & Company.

Taubes explains the premise of NuSI:

NuSI was founded on the premise that the reason we are beset today by epidemics  of obesity and type 2 diabetes, and the reason physicians and researchers think these diseases are so recalcitrant to dietary therapies, is because of our flawed understanding of their causes. We believe that with a concerted effort and the best possible science, this problem can be fixed.

NuSI originally started as a more modest endeavor, but has now received a significant commitment of financial support from a foundation started by billionaire hedge fund manager John Arnold. The aim of the organization is, as the following NuSI publicity slide states, to “create a Manhattan Project-like effort to solve” the problem of obesity in the US:

The NuSI scientific advisory board is composed of Alan Sniderman, a lipid researcher at McGill University, David Harlan, the former head of the Diabetes, Endocrinology, & Metabolic Diseases branch of the NIDDK and now at U Mass, Mitchel Lazar, of the University of Pennsylvania, and Kevin Schulman, of Duke University.

On his Weighty Matters blog, obesity clinician and writer Yoni Freehoff offers a perspective both critical and supportive of the NuSI agenda.

Click here to read the NuSI press release…

Reports From JUPITER And Taiwan: Benefits Of Statins Outweigh Risk Of Diabetes 1

Two new papers provide further evidence that statin usage is associated with an increased risk of diabetes, but both studies also find that the benefits of statins still outweigh the risks.

In the first report, published in the Lancet, Paul Ridker and colleagues analyze data from the JUPITER trial, which compared rosuvastatin to placebo in a primary prevention population.

Among the 17,603 patients randomized in the trial, 11,508 had at least one major risk factor for developing diabetes. In this group, the primary endpoint (MI, stroke, hospitalization for unstable angina, revascularization, or CV death) was reduced by 39% in the statin group (hazard ratio 0·61, CI 0.47–0.79, p=0·0001). The authors calculated that in the statin group 134 vascular events or deaths were avoided  for every 54 new cases of diabetes. For the 6,095 patients without a major risk factor for diabetes, the primary endpoint was reduced by 52%  (HR 0·48, CI 0.33–0.68, p=0·0001). No increase in diabetes was observed. In this group, 86 vascular events or deaths were avoided.

During the JUPITER trial 486 subjects developed diabetes  (270 in the rosuvastatin group and 216 in the placebo group). The risk reduction in this group was consistent with the overall reduction observed in the trial.

“Our results show that in participants with and without diabetes risk, the absolute benefits of statin therapy are greater than the hazards of developing diabetes,” said Paul Ridker, in a press release issued by the Lancet. “We believe that most physicians and patients would regard heart attack, stroke and death to be more severe outcomes than the onset of diabetes, and so we hope that these results ease concern about the risks associated with statin therapy when these drugs are appropriately prescribed – in conjunction with improved diet, exercise and smoking cessation – to reduce patients’ risk of cardiovascular disease.”

The findings from JUPITER were echoed in a large observational study from Taiwan published in the Journal of the American College of Cardiology that compared 8,412 people receiving statins with 33,648 matched controls. The Taiwan investigators found that although, over a median of 7.2 years, the rate of diabetes was significantly higher among statin users  (2.4% vs. 2.1%, p < 0.001), statins were associated with a significant reduction in cardiovascular events (HR 0.91, CI 0.84 to 0.99, p = 0.031).
Click here to read the Lancet press release…

AHA And ADA Cautiously Endorse Non-Nutritive Sweeteners 1

In a newly released scientific statement the American Heart Association and the American Diabetes Association offer a cautious endorsement of the use of non-nutritive sweeteners in the diet. But the statement notes that the products are not “magic bullets” and that there is no strong evidence demonstrating beneficial effects of the products.

Sugar in the diet has been linked repeatedly to obesity, type 2 diabetes, and cardiovascular disease, leading to recommendations that sugar intake should be limited. However, the evidence to date is “inconclusive” that non-nutritive sweeteners (including aspartame, acesulfame-K, neotame, saccharin, sucralose, and stevia) can reduce caloric intake, lower body weight, or help prevent diabetes or cardiovascular disease.

“Determining the potential benefits from non-nutritive sweeteners is complicated and depends on where foods or drinks containing them fit within the context of everything you eat during the day,” sad Christopher Gardner, one of the authors of the report, in an AHA press release. “For example, if you choose a beverage sweetened with non-nutritive sweeteners instead of a 150-calorie soft drink, but then reward yourself with a 300-calorie slice of cake or cookies later in the day, non-nutritive sweeteners are not going to help you control your weight because you added more calories to your day than you subtracted.”

“However, if you substitute the beverage with non-nutritive sweeteners for a 150-calorie sugar-sweetened soft drink, and don’t compensate with additional calories, that substitution could help you manage your weight because you would be eating fewer calories,” said Gardner.

The following text is taken from the summary and recommendations of the report:

At this time, there are insufficient data to determine conclusively whether the use of NNS to displace caloric sweeteners in beverages and foods reduces added sugars or carbohydrate intakes, or benefits appetite, energy balance, body weight, or cardiometabolic risk factors…. There are some data to suggest that NNS may be used in a structured diet to replace sources of added sugars and that this substitution may result in modest energy intake reductions and weight loss. Successful reduction in energy intake requires that there is incomplete compensation of energy reduction from the use of NNS containing beverages and/or foods. The impact of incorporating NNS and NNS-containing beverages and foods on overall diet quality should be included in assessing the overall balance of benefits and risks.

Addressing the negative perception of non-nutritive sweeteners that many people have developed,  weight loss expert and blogger Yoni Freedhoff sent the following comment to CardioBrief:

Likely consequent to the natural fallacy many readily assume that the consumption of NNS carries risk, included among them a risk towards increased consumption and weight gain.  It’s refreshing then to see the analysis of actual evidence on the use of NNS in people rather than animal models concludes that if anything there’s a suggestion of benefit to weight management, rather than risk, with the consumption of NNS.  Given the complexity of weight regulation and human behavior, no intervention will work in a vacuum and my clinical experience definitely suggests a synergy between their use and true caloric literacy and may help to explain the lackluster results.  Hopefully future studies will shine more conclusive light on the situation.”

(Editor’s note: The publication of this statement had been embargoed until 4 PM ET today. However, the AHA appears to have published the statement ahead of schedule and then tweeted it.)

Click here to read the AHA press release…

Linagliptin And Glimepiride Compared In Type Two Diabetes Reply

Sulfonylureas are often added to metformin to improve glycemic control, but at the known risk of increasing hypoglycemia and weight gain. In a report published in the Lancet, more than 1,500 patients with type 2 diabetes taking metformin were randomized to the addition of either linagliptin, a dipeptidyl peptidase-4 inhibitor or the sulfonylurea glimepiride.

After two years the trial achieved the prespecified criterion for noninferiority as treatment with both drugs resulted in a similar effect on HbA1c. Both hypoglycemia and weight gain were reduced in patients taking linagliptin. There was only one case of severe hypoglycemia in the linagliptin group, compared with 12 cases in the glimepridie group. In addition, although there were only a small number of cardiovascular (CV) events, a significant reduction was observed in the linagliptin group.

  • Reduction in mean HbA1c: −0.16% for linagliptin versus −0.36% for glimepiride (difference 0.20%, CI 0.09–0.30)
  • Hypoglycemia: 7% for linagliptin versus 36% for glimepiride (p<0·0001)
  • Weight: −1.4 kg versus  +1.3 kg (p<0·0001)
  •  CV events: 12 vs 26 events, RR 0.46, CI 0.23—0.91 (p=0.0213)

The results, write the authors, “support the use of linagliptin in combination with metformin as a therapeutic option for treatment of type 2 diabetes.”

In an accompanying editorial, André Scheen and Nicolas Paquot discuss the potential benefits of linagliptin and other DPP-4 inhibitors. They note that the smaller reduction in HbA1c with linagliptin “might support the view of a slightly lower efficacy of DPP-4 inhibitors compared with sulphonylureas,” but  say that only a trial with longer followup can assess the durability of of glucose lowering with DPP-4 inhibitors. In the meantime, the effects on weight and the lower rate of hypoglycemia are “important to patients with diabetes” and can improve quality of life.

However, firm conclusions about the drugs can not be reached until long-term trials with cardiovascular outcomes are completed. These trials will “provide enough data for both efficacy (ie, effects on diabetic complications) and safety (ie, concerns about pancreatitis and pancreatic cancer) to draw firm conclusions about the real value of this new approach.”
Click here to read the press release from the Lancet…

Guest Post– Reality Check: The ORIGIN of Spin in a Randomized Trial 2

Editor’s Note: The following guest post is reprinted with permission from CardioExchange, the cardiology social media website published by the New England Journal of Medicine. Steven Coca is a nephrologist at the Yale School of Medicine. 

Reality Check: The ORIGIN of Spin in a Randomized Trial

by Steven Coca, DO, MS

In the ORIGIN randomized trial, involving about 12,500 people who had diabetes or were at risk for it, insulin glargine showed no advantage over standard care in preventing the primary composite cardiovascular endpoints at a median follow-up of 6.2 years (see news coverage on CardioExchange). ORIGIN was a completely negative trial, yet in the article’s abstract the authors reported a benefit of basal insulin in the secondary endpoint of incident diabetes (odds ratio [OR], 0.80; 95% CI, 0.64–1.00; P=0.05) and stated that the treatment “reduced new-onset diabetes.” The discussion section of the paper further asserted that the treatment “slowed progression of dysglycemia.”

A few qualifications are in order:

1. This seemingly positive finding (in incident diabetes) was for only one of several secondary endpoints, and the alpha level needed to detect a difference was not corrected for multiple outcome assessments.

2. Among the 1456 participants without diabetes at randomization, only 44% of insulin glargine recipients and 47% of standard-care recipients underwent both prespecified oral glucose tolerance tests at the end of the study. So, in effect, fewer than half of the patients were assessed on the one, barely positive endpoint of incident diabetes. Plus, the fact that an absolute 3% more of the control group underwent the necessary testing could have resulted in ascertainment bias.

3. Incident diabetes among those 1456 participants was much greater than 10% (30% in the insulin glargine group, 35% in the standard-care group), but the authors reported an odds ratio rather than a relative risk, yielding an overinflation of the purported benefit  The relative risk would have been 0.86, compared with the reported OR of 0.80. (Only when the probability of a disease is low does the odds ratio approximate the relative risk.)

4. The upper boundary of the confidence interval included 1.00.

Despite these realities, Sanofi and the investigators didn’t hesitate to “spin” the trial findings to the media. The Sanofi press release stated, “…the results also showed that insulin glargine delayed progression from pre-diabetes to type 2 diabetes.” Sanofi’s VP of Medical Affairs said, “ORIGIN shows that it is possible to maintain low and stable HbA1c levels that are close to normal over a long time, and to potentially delay the progression from pre-diabetes to diabetes.” One of the lead investigators took this positive angle: “We know that in this study, insulin lowered blood sugar levels and did so safely and effectively. I can look at a patient and say, ‘Your blood sugar is not well controlled right now, so let’s go ahead and add insulin’.”

There is a temptation for those involved in a trial to present findings as positive, even if the positive aspect is only a morsel. However, scientists should stick to the facts. The first sentence of the abstract of this paper asked whether “the provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events.” The results of the trial tell us that the answer is simply “No.”

How did you read the ORIGIN trial? What’s your take on the facts versus the spin?

Is Chronic Kidney Disease A CHD Risk Equivalent? Reply

A new study published in the Lancet provides new data about whether chronic kidney disease (CKD) should, like diabetes, be considered a coronary heart disease (CHD) risk equivalent.

Marcello Tonelli and colleagues analyzed data from a population of 1.25 million people in Alberta, Canada. During a median followup of 4 years, 11,340 people were admitted to the hospital for MI. People with a previous MI were at higher risk for MI admission than people with either diabetes or CKD:

  • MI history: 18.5 per 1000 person-years (CI 17.4–19.8)
  • Diabetes: 5.4 per 1000 person-years (5.2–5.7)
  • CKD: 6.9 per 1000 person-years (6.6–7.2)
After adjustment for other variables, the relative rate of MI was lower in the CKD group than in the diabetes group (rate and adjusted relative rate for MI admission):
  • Previous MI: 7.7%, RR 3.8 (CI 3.5-41)
  • Diabetes and CKD: 6%, RR 2.7 (2.5-2.9)
  • CKD: 2.8%, RR 1.4 (1.3-3.5)
  • Diabetes: 2.4%, RR 2.0 (1.9-2.1)
  • No diabetes or CKD: 0.5%, RR 1 (reference)

The authors write that their “data show that diabetes alone and chronic kidney disease alone… do not increase the rate of myocardial infarction to the same extent as does a history of coronary disease, and therefore do not support the use of the term coronary heart disease risk equivalent for either disorder.” However, they concluded that CKD should “be added to the list of criteria defining people at highest risk of future coronary events.”

In an accompanying comment, Tamar Polonsky and George Bakris write that “despite negative findings for the primary outcome, compelling reasons are provided to consider lipid-lowering therapy in patients with chronic kidney disease.”
Click here to read the Lancet press release…

Transient Glucose Regulation Helps Prevent Progression To Diabetes In Prediabetics Reply

Prediabetics– people with impaired fasting glucose or impaired glucose tolerance– can reduce their high risk of progressing to diabetes if they achieve even a transient return to normal glucose regulation, according to results of the Diabetes Prevention Program Outcomes Study (DPPOS), presented at the American Diabetes Association meeting and published simultaneously online in the Lancet.

Leigh Perreault and colleagues in the Diabetes Prevention Program Research Group analyzed data from 1,990 participants who had been randomized in the original DPP study to either intensive lifestyle intervention, metformin, or placebo. The risk of developing diabetes was significantly lowered by 56% in the study subjects who at some point during the DPP study had normal glucose regulation compared with those who continued to have prediabetes (hazard ratio 0.44, CI 0.37–0.55, p<0.0001). Diabetes prevention was strongly correlated with the number of times subjects were found to have normal glucose regulation.

For diabetes prevention it didn’t matter to which treatment group people were assigned if they attained normal glucose regulation at some point. However, people randomized to intensive lifestyle intervention who remained consistently prediabetic were more likely to develop diabetes.

The investigators wrote that the results of their study suggest “that the strategy is unimportant as long as the intervention is early (when someone has prediabetes) and can restore normal glucose regulation, even if transiently. Further, maintenance of prediabetes despite the potent glucose-lowering effects of intensive lifestyle modification represents a high-risk state and might warrant additional preventive strategies.”

In an accompanying comment, Natalia Yakubovich and Hertzel Gerstein write that “identification of regression to normoglycemia could be an important way to stratify people into those at higher and lower risk of progression to diabetes. Such stratification could therefore identify individuals for whom additional treatment might be needed to prevent diabetes or to slow down disease progression.”
Click here to read the Lancet press release…

Bariatric Surgery Turns Back the Clock on Diabetes 2

Two new randomized trials offer new evidence that bariatric surgery is highly effective in obese patients with diabetes. The results, according to Paul Zimmet and K. George M.M. Alberti, writing in an editorial in the New England Journal of Medicine, “are likely to have a major effect on future diabetes treatment.”

In the STAMPEDE trial, which was presented at the American College of Cardiology and published simultaneously in the New England Journal of Medicine,  150 obese patients with uncontrolled type 2 diabetes were randomized to medical therapy alone or medical therapy plus either Roux-en-Y gastric bypass or sleeve gastrectomy. Philip Schauer presented the main results.

Percent of patients with glycated hemoglobin level of 6% or less at 1 year:
Click to continue reading…

Statins and Diabetes: Real Concern or Much Ado About Nothing? 6

Updated at 7 PM with a detailed comment at the bottom from C. Michael Minder of Johns Hopkins–

In New York Times Op-Ed piece on Monday, Eric Topol comments on last week’s announcement by the FDA that it was changing the label for statins. Topol focuses on the new warning that statins raise the risk of diabetes. He opens with a provocative statement:

We’re overdosing on cholesterol-lowering statins, and the consequence could be a sharp increase in the incidence of Type 2 diabetes.

Topol does the math and calculates that 20 million Americans taking statins equates to 100,000 new statin-induced diabetics:

Not a good thing for the public health and certainly not good for the individual affected with a new serious chronic illness… If there were a major suppression of heart attacks or strokes or deaths, that might be justified. But in patients who have never had heart disease and are taking statins to lower their risk (so-called primary prevention), the reduction of heart attacks and other major events is only 2 per 100. And we don’t know who the 2 per 100 patients are who benefit or the one per 200 who will get diabetes! Moreover, the margin of benefit to risk is quite narrow.

Topol then concludes that statins are beneficial for secondary prevention in people with a history of heart disease or stroke but for “the vast majority of people who take statins — those who have never had any heart disease — there should be a careful review of whether the statin is necessary, in light of the risk of diabetes and the relatively small benefit that can be derived.”
Click to continue reading…