A Clinical Context Report

Transcription

1 Type 2 Diabetes in Practice An Expert Commentary with Silvio E. Inzucchi, MD A Clinical Context Report

2 Clinical Context: Type 2 Diabetes in Practice Expert Commentary Jointly Sponsored by: and

3 Clinical Context: Type 2 Diabetes in Practice Expert Commentary This activity is supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. which was made possible, in part, through a collaboration with Eli Lilly and Company.

4 Type 2 Diabetes in Practice Clinical Context Series The goal of this series is to provide up-todate information and multiple perspectives on the pathogenesis, patient identification, symptoms, risk factors, current and emerging treatments, and best practices in the management of type 2 diabetes.

5 Type 2 Diabetes in Practice Clinical Context Series Target Audience Endocrinologists, cardiologists, diabetes educators, primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the care of patients with type 2 diabetes.

6 Activity Learning Objective Upon successful completion of this educational program, participants should be able to: l Review the relevance and significance of the activity in the broader context of clinical care.

7 CME Information: Physicians l Statement of Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Projects In Knowledge and MedPage Today. Projects In Knowledge is accredited by the ACCME to provide continuing medical education for physicians.

8 CME Information l Credit Designation Projects In Knowledge designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

9 CME Information: Physicians l Credit for Family Physicians MedPage Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, Term of approval is for one year from this date. Each article is approved for 0.5 Elective credits. Credit may be claimed for one year from the date of each article.

10 CE Information: Nurses l Statement of Accreditation Projects In Knowledge, Inc. (PIK) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center s Commission on Accreditation. Projects In Knowledge is also an approved provider by the California Board of Registered Nursing, Provider Number CEP This activity is approved for 0.50 nursing contact hours. There is no fee for this activity. DISCLAIMER: Accreditation refers to educational content only and does not imply ANCC, CBRN, or PIK endorsement of any commercial product or service.

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12 Discussant Silvio E. Inzucchi, MD Professor of Medicine Clinical Director, Section of Endocrinology Director, Yale Diabetes Center Director, Endocrinology & Metabolism Fellowship Director, Yale Affiliated Hospitals Program New Haven, Connecticut

13 Disclosure Information Silvio Inzucchi, MD, has disclosed the following relevant financial relationships: Salary/Honoraria: Over the past 12 months, has served on advisory boards or, has consulting agreements from: Boehringer Ingelheim, Merck, and Takeda Research/Support from: Eli Lilly, and Takeda

14 Disclosure Information Dori F. Zaleznik, MD, Associate Clinical Professor of Medicine, Harvard Medical School, Boston; Kristina Fiore; and Dorothy Caputo, MA, BSN, RN, Nurse Planner, have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staffs of Projects In Knowledge and MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

15 ADA/EASD Guidelines for Hyperglycemia Clinicians should take an individualized, patientcentric approach to therapeutic management of type 2 diabetes 1 After metformin, no second-line agent is a clear winner 1. Inzucchi SE, et al Management of hyperglycemia in type 2 diabetes: a patientcentered approach. Position statement of the ADA and EASD

16 Individualization of Therapy Much individualization is based on adverse effects Sulfonylureas and insulin not ideal for patients at high risk of hypoglycemia TZDs not optimal for those with baseline edema or in women with osteoporosis Avoid GLP-1 agonists in patients who can t tolerate GI effects DPP-4 inhibitors have mild side effects but are less potent

17 Thiazolidinediones (TZDs) Risks still unclear Caution arose with 2007 study linking Avandia with MI 2 Actos included in ADA/EASD guidelines, appears to improve CV complications overall However, concerns remain about Actos and risks of heart failure due to fluid retention, fractures in women, and bladder cancer 2. Nissen SE, Wolski K Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes N Engl J Med 2007; 356.

18 Early Aggressive Management Recent Lancet study found insulin as second-line agent improves glycemic control over sitagliptin 3 Patients may prefer pill over injection Most clinicians still use insulin as third-line agent 3. Achsner P, et al Insulin glargine versus sitagliptin in insulin-naïve patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicenter, randomized, open-label trial Lancet 2012; DOI: /S (12)

19 ACCORD - ADVANCE - VADT Trials found no cardiovascular benefits for aggressive glycemic control Caveat: trials recruited patients with advanced disease Aggressive management may improve microand macrovascular complications if done early on in disease course, but benefits may not be seen for decades

20 Attempting Early Aggressive Management Focus on lifestyle: diet and exercise alone can help significantly reduce HbA1c Metformin is the preferred first-line therapy after diet and exercise After metformin, use combination therapy with an SU, TZD, DPP-4 inhibitor, GLP-1 agonist or insulin GLP-1 agonist as third-line therapy may be as potent as insulin

21 In the Pipeline About 10 to 15 classes under investigation Many will never make it to market SGLT-2 Inhibitors: Canagliflozin Dapagliflozin (received thumbs-down from FDA advisory committee) Empagliflozin Block reabsorption of glucose by kidney Side effects: UTI, yeast infections

22 In the Pipeline (continued) Glucagon receptor agonists Glucokinase activators 11-beta-HSD inhibitors Very early in development

23 Summary At the end of this activity, participants should understand: l l l l Joint guidelines from ADA and EASD recommend a highly individualized approach to the management of type 2 diabetes. After lifestyle modification and metformin, there is no clear winner among second-line agents. Reasonable choices: sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 agonists and basal insulin Most individualization of therapy is based on the adverse effects associated with each agent.

24 Summary (cont.) Sulfonylureas and insulin should be avoided if possible in patients at high risk of hypoglycemia. TZDs are not recommended for patients who should not gain more weight, or for women with osteoporosis and those at risk of fracture Patients who cannot tolerate gastrointestinal side effects aren t the best candidates for GLP-1 agonists. DPP-4 inhibitors have milder side effects but are less potent.

25 Summary (cont.) l l l Some studies have shown that when aggressive management is started early, it may hold cardiovascular benefits further down the line. Trials that have found little benefit for early aggressive management were largely conducted in patients with advanced disease, which may skew the results. Clinicians can practice early aggressive management by strongly encouraging significant lifestyle changes when the disease is first diagnosed.

26 Summary (cont.) l l l There are several new agents coming down the pike, notably the SGLT-2 inhibitors SGLT-2s work by dumping excess glucose into the urine, which appears to up the risk of genitourinary infections. Investigational agents, such as other glucagon receptor agonists and glucokinase activators, are still very far from clinical use.