Skip to main content

ADA/EASD Issue New Hyperglycemia Management Guidelines


April 19, 2012 — The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have issued a joint position statement emphasizing patient-specific treatment of hyperglycemia in persons with type 2 diabetes. The new guidelinesare reported concurrently in the April 19 online edition of Diabetes Care and in Diabetologia.
"All guidelines are in a state of evolution based on new information, and the overall standard of care is updated every January," Vivian Fonseca, MD, ADA president of medicine and science, told Medscape Medical News in a telephone interview.
The last guidelines specific to management of hyperglycemia were published about 4-5 years ago, and more recent developments have been incorporated into the new guidelines."
The impetus underlying the new guidelines was the growing complexity and controversy surrounding contemporary glycemic management in persons with type 2 diabetes. Factors complicating management include the increasing number and variety of available pharmacotherapy, issues regarding potential adverse effects, and new uncertainties concerning the effects of intensive glycemic control on macrovascular complications.
Dr. Fonseca, who is also professor of medicine and endocrinology at Tulane University in New Orleans, Louisiana, explained that there has been a small change in what the optimal blood glucose goal should be. On the basis of findings from ACCORD (Action to Control Cardiovascular Risk in Diabetes study) and other studies, the ADA has set the HbA1c goal at 7% in general, but with some individualization.
"For patients with advanced cardiovascular disease, reduced life expectancy, and multiple medical problems, for example, the goal may be higher," Dr. Fonseca said. "For patients who are newly diagnosed and very motivated, the goal may be lower."
Another recent change underlying the new guidelines is the recognition that many people with diabetes will need multiple agents. For example, the dipeptidyl peptidase-4 (DPP4) inhibitors have become available since the last hyperglycemia guideline was published.
Patient-Centered Management
Rather than using clearly defined algorithms, the new guidelines are less prescriptive and more patient-centered. Recommendations are tailored to individual patient needs, preferences, and tolerances and are based on differences in age and disease course. Other factors affecting individualized treatment plans include specific symptoms, comorbid conditions, weight, race/ethnicity, sex, and lifestyle.
"We start with metformin, and if the patient is not meeting goal in 3 months, we change therapy based on patient-specific factors," said Dr. Fonseca, who was not involved in writing the new guidelines.
"There have been no good studies comparing all available treatment strategies, so we base the decision on individual factors such as willingness to self-inject, or need for weight loss. If that fails, we try another option. There is no clear-cut decision tree as there was in the previous hyperglycemia guideline, because this guideline is more patient-centric."
The position statement mandates diabetes education for all patients, to be administered to individuals or groups. The curriculum should highlight dietary intervention and the key role of increased physical activity and weight management, when appropriate, in an individual or group setting.
"The new guideline should actually be easier for physicians to implement because there is greater flexibility in management, offering a road map rather than a single path," Dr. Fonseca concluded. "The ADA guidelines in general are already fairly widely implemented, and we are seeing benefits from that. Over the past 10-15 years, HbA1c has been dropping, and over the past year, there has started to be a drop in rates of diabetes-related blindness, retinopathy, dialysis, and amputation. But there still remain a large number of patients with these outcomes, so we still have a ways to go."
Key Points
Key recommendations in the new ADA/EASD statement include the following:
  • Glycemic targets and treatments to lower glucose must be individualized according to specific patient characteristics.
  • The mainstay of any type 2 diabetes treatment program is still diet, exercise, and education.
  • Metformin is the preferred first-line drug, in the absence of contraindications.
  • Data are limited regarding use of agents other than metformin. A reasonable approach is combination therapy with 1 to 2 additional oral or injectable agents, with the goal of minimizing side effects to the extent possible.
  • To maintain glycemic control, many patients will ultimately need insulin monotherapy or in combination with other medications.
  • Whenever possible, the patient should participate in all treatment decisions, focusing on their preferences, needs, and values.
  • A major treatment goal must be comprehensive cardiovascular risk reduction.
Others Weigh in on the New Guidelines
In an accompanying editorial, Diabetes Care editor William Cefalu, MD, notes that some experts prefer an algorithm-based management plan offering consistent treatment guidelines, whereas others favor flexible treatment options based on specific pathophysiology.
"The most attractive aspect of the new position statement is that more than any other previously reported guidelines to date, it clearly emphasizes that 'one size clearly does not fit all'," Dr. Cefalu writes.
EASD President Andrew J.M. Boulton also commended the new guidelines for their patient-specific approach.
"The new guidelines were prepared using the best available evidence," Dr. Boulton said in a news release. "Diabetes is a condition which affects people in a multitude of ways: the new guidelines take a more holistic approach, focusing on treating the patient as an individual and understanding that treatments need to be 'made to measure,' an approach that will likely improve not only patient care, but also quality of life."
The statement authors report various financial disclosures with Abbott Diabetes Care, Amylin, Bayer, Becton Dickinson, Boehringer Ingelheim, Calibra, DexCom, Eli Lilly, Halozyme, Helmsley Trust, Hygieia, Johnson & Johnson, Medtronic, National Institutes of Health, Novo Nordisk, Roche, Sanofi, Takeda, Merck, AstraZeneca, Biodel Inc; Bristol-Myers Squibb, Diartis Pharmaceuticals Inc, F. Hoffmann-La Roche, Halozyme Therapeutics, Medtronic MiniMed, Pfizer Inc, TransPharma Medical Ltd, Poxel Pharma, Astra-BMS, GlaxoSmithKline, Novartis, Servier,Tolerx, Berlin-Chemie, Diartis, Intarcia Therapeutics, sanofi-aventis Pharma, Versartis, MSD, and/or Merck Serono. Dr. Fonseca states that he has no conflicts of interest regarding the new guidelines. He has been involved in research trials funded by Novo Nordisk, sanofi-aventis, Eli Lilly, Reata, Abbott, Mesoblast, Pan-American Laboratory, and Takeda. He has been a consultant for Takeda, Novo Nordisk, sanofi-aventis, Eli Lilly, Pan-American Laboratory, Daichi-Sankyo, Xoma, Astra Zeneca, Abbott, Bristol-Myers Squibb, and GlaxoSmithKline.

Comments

Popular posts from this blog

Missing Data Lead FDA Panel to Vote Against Rivaroxaban for ACS May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting, the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel, or ticlopidine. Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . The 'missingness' of the data doesn't invalidate it, but it certainly makes it hard to infer [the conclusion]." Dr Steven Nissen (Cleveland Clinic, OH) said that the decision to use the modified intention-to-treat analysis had a "profound impact" on the interpretability of the data. "It's saying we don't care what happens after 30 days, [and] that colored the trial in ways we couldn't recover from." Given the risk of major bleeding, "I want to see better evidence that this strategy of adding an Xa inhibitor or a direct thrombin inhibitor or something else to a good antiplatelet agent is robustly better for the patient," Nissen said. He recommends that the companies run a new trial of the 2.5 twice-daily dose of rivaroxaban using a strict intention-to-treat approach, but, he said, "I don't expect the death benefit to be too robust." Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. "What I want to know is, among the people who had events, how differential was the follow-up, but I can tell you by just looking at it, there was a very slightly different amount of follow-up of the people in the treatment arm. But I don't know whether everyone in the treatment arm was cured and they were trekking in the Himalayas and everyone in the placebo arm went home to die. I don't know that that's not the case." Dr Maury Krantz (University of Colorado, Denver) voted in favor of approval but said he does not know how rivaroxaban would perform in general clinical practice, especially when used with aspirin and clopidogrel. "I felt very much torn by this. This isn't a simple paradigm shift. It means going to triple therapy, which is really a three-headed monster in many ways. I think that what you're going to see in practice, if this is not done carefully with the proper labeling and secondary studies, is really dramatic magnification of bleeding and perhaps minimization of the efficacy benefit."

May 23, 2012   (Updated May 24, 2012)  (Silver Spring, Maryland)  —  The missing data issues plaguing the  ATLAS ACS 2 TIMI 51   trial of the factor Xa inhibitor  rivaroxaban  (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the  FDA  Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting , the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus  clopidogrel , or  ticlopidine . Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the  ATLAS ACS TIMI 46   phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the ri...

Antidepressants Linked to Higher Diabetes Risk in Kids

Pediatric patients who use antidepressants may have an elevated risk for type 2 diabetes, the authors of a new study report. In a retrospective cohort study of more than 119,000 youths 5 to 20 years of age, the risk for incident type 2 diabetes was nearly twice as high among current users of certain types of antidepressants as among former users, Mehmet Burcu, PhD, and colleagues report in an article  published online October 16 in  JAMA Pediatrics . The risk intensified with increasing duration of use, greater cumulative doses, and higher daily doses of these antidepressants. The findings point to a growing need for closer monitoring of these products, including greater balancing of risks and benefits, in the pediatric population, the authors caution. They undertook the study because, despite growing evidence of an association between antidepressant use and an increased risk for type 2 diabetes in adults, similar research in pediatric patients was scarce. "To our know...

Sitting at Work Raises All-Cause and CV Mortality Risk

May 21, 2012 (Lyon, France) — Sitting at work raises the risk of dying from cardiovascular (CV) and metabolic diseases, as well as the risk of dying from all causes, regardless of any exercise in which the individual may engage. That was the finding of a study reported here at the 19th European Congress on Obesity (ECO) by Anne Grunseit, PhD, from the Prevention Research Collaboration in the School of Public Health at the University of Sydney, Australia, and Norwegian colleagues. Research is increasingly focusing on sedentary behavior with low energy expenditure, including sitting and lying down, as behavioral risk factors for obesity and chronic disease. Sitting occurs during travel, while watching television, using computers, and reading. But with people often spending at least 9 hours a day at work, with fewer than 20% of jobs requiring physical exertion, and with many people spending at least 4 hours a day sitting at work, the sedentary time at work is high, and many people ar...