New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Emerging Challenges in Primary Care: Update 2013

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Faculty •  Robert S. Busch, MD, FACE Managing Partner of The Endocrine Group, LLP, Albany, NY

•  Luigi F. Meneghini, MD, MBA Professor of Clinical Medicine, Division of Endocrinology, Diabetes & Metabolism Director, Kosow Diabetes Treatment Center, Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL

•  Mark Stolar, MD Associate Professor of Clinical Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 2

NACE – Emerging Challenges in Primary Care: Update 2013

Diabetes - 1

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Faculty Disclosure •  Robert S. Busch, MD, FACE –  Speakers Bureau - Merck, Janssen, Bristol Myers Squibb and Novo Nordisk

•  Luigi F. Meneghini, MD, MBA –  Advisory Board - Novo Nordisk and Halozyme –  Consultant - Novo Nordisk and Sanofi –  Researcher - MannKind, Pfizer, Boehringer Ingelheim, Biodel and Sanofi Aventis (pending)

•  Mark Stolar, MD –  Advisory Board – Takeda –  Speaker - Vivus

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Learning Objectives for Discussion: •  Discuss the role of the kidney in the pathophysiology of diabetes in health and disease •  Discuss the role of glycemic control in the pathogenesis of microvascular complications •  Discuss the physiology of SGLT-2 in glucose metabolism •  Discuss the role of SGLT-2 inhibitor therapy in management of diabetes and possible impact on other metabolic risk factors

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NACE – Emerging Challenges in Primary Care: Update 2013

Diabetes - 2

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Pre-Test Question 1

ON A SCALE OF 1 TO 5, PLEASE RATE HOW CONFIDENT YOU ARE IN RECOGNIZING THE ROLE OF SGLT2-INHIBITORS IN THE MANAGEMENT OF DIABETES 1.  Not at all confident 2.  Slightly confident 3.  Moderately confident 4.  Pretty much confident 5.  Very confident

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Pre-Test Question 2

Which of the following is incorrect about the kidney in diabetes? 1.  Serum creatinine and eGFR are equally predictive of renal function in diabetes 2.  The kidney contributes 20-25% of all glucose output in the fasting state and 40% of all gluconeogenesis 3.  Renal glucose production is increased in the diabetic postprandial state contributing to hyperglycemia 4.  The risk of hypoglycemia is significantly increased in renal impairment

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NACE – Emerging Challenges in Primary Care: Update 2013

Diabetes - 3

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Pre-Test Question 3

Which of the following is incorrect regarding metabolic memory and the legacy effect? 1.  It is likely mediated by oxidative stress induced changes in the mitochondria 2.  May be mediated by advanced glycosylated end products (AGE’s) 3.  Both the EDIC and UKPDS trials demonstrated the presence of an enduring legacy effect. 4.  Clinical trials have consistently shown that early aggressive treatment of diabetes will reduce long term risk of complications 5.  VADT trial did not show significant benefit of intensive control on complication risk

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Pre-Test Question 4

Which of the following is incorrect about SGLT-2 physiology in the kidney? 1.  10% of all glucose filtered by the kidney are reabsorbed by these receptors 2.  SGLT-2 activity is upregulated in diabetes 3.  SGLT-2 inhibition causes natriuresis and a drop in systolic and diastolic blood pressure 4.  SGLT-2 inhibition of glucose uptake by renal cells may reduce progression of diabetic kidney disease

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NACE – Emerging Challenges in Primary Care: Update 2013

Diabetes - 4

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Pre-Test Question 5

Which of the following does not occur with use of SGLT-2 Inhibitors? 1.  2.  3.  4.  5. 

lowering of A-1c by 0.5-0.7% lowering of LDL-cholesterol lowering of blood pressure increased glucose excretion in urine decreased body weight

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Challenges in Type 2 Diabetes

•  Progressive worsening of insulin secretory deficit requiring increased number of antihyperglycemic medications over time •  Treatment models do not match disease state understanding •  Risk for hypoglycemia, weight gain and ? CV risk with some therapies •  Preventing and managing complications and co-morbidities of renal dysfunction and cvd •  Difficulty attaining and sustaining optimal long-term glycemic control

CDC  2010.  Na*onal  Diabetes  Fact  Sheet.  US  Department  of  Health  and  Human  Services.   Cefalu,  WT.  Am  J  Med.  2012;343(1):21-­‐26.    

NACE – Emerging Challenges in Primary Care: Update 2013

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Diabetes - 5

New Therapies in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

Type 2

UKPDS: Correlation Between A1C and Microvascular Endpoints Microvascular endpoints* 10 Hazard ratio (log scale)

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