The ABCs (A1C, BP and Cholesterol) of Diabetes

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1 The ABCs (A1C, BP and Cholesterol) of Diabetes Gregg Simonson, PhD Director, Professional Training and Consulting International Diabetes Center; Adjunct Assistant Professor, University of Minnesota Department of Family Practice Dr. Simonson is on the advisory board for Merck & Co., Inc. In the past 12 months, all of Dr. Simonson s industry sponsored consultancy work was performed under contract to the non-profit Park Nicollet Institute and the International Diabetes Center of which Dr. Simonson is a salaried employee. He does not intend to discuss any unapproved/investigative use of a commercial product/device. Faculty Disclosures Dr. Simonson is a member of the Merck Scientific Advisory Board. He does not receive personal honorarium instead all honorarium support the non-profit International Diabetes Center at Park Nicollet. He does not intend to discuss any unapproved / investigative use of commercial product / device.

2 International Diabetes Center Ensuring that every individual with diabetes or at risk for diabetes receives the best possible care Priorities of Care for Older Adults with Diabetes Diagnosis Prevention Dx A1C 6.5%, fasting glucose 126 casual symptoms prevent pre-diabetes (IFG-IGT) & metabolic syndrome Self-Management Knowledge and Skill Monitoring Medication Problem solving Food plan & nutrition Risk reduction Living & coping Physical activity Emotional Health Glucose Lipids Hypertension Microvascular complications Other essentials of care A 2015 International Diabetes Center.

3 Glycemic Targets for Type 2 Diabetes Recommendations by American Diabetes Association Time General Population A1C <7% Fasting/ Premeal (individualized) Older Healthy Older Complex Older Very Complex Poor Health <7.5% <8.0% <8.5% mg/dl mg/dl mg/dl mg/dl Bedtime Not specified mg/dl mg/dl mg/dl Rationale: the longer life expectancy the tighter glycemic control and reducing treatment burden and hypoglycemia risk for patients in older more complex patient in poor health ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1 Benefits of Moderate Glycemic Control Enhancement of wound healing Less dehydration (polyuria) Increased energy Maximize cognitive function Mood improved Lower risk of hyperglycemic hyperosmolar coma ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

4 Avoid Hypoglycemia Hypoglycemia can lead to falls Frail, older adults are at higher risk for serevere hypoglycemia Patients with cognitive impairment at higher risk Potential Causes Not following food plan Impaired renal and/or liver function Misdiagnosis due to dementia, delirium, depression, seizures, CVA Feil, DG et al, Risk of Hypoglycemia in Older Veteran with Dementia, JAGS 2011;59: Why should metformin be considered firstline therapy for older patients with type 2 diabetes? Efficacious and durable therapy Low risk of hypoglycemia Weight neutral, modest improvement in lipids Many years of experience Lower cost Effective in combination therapy (many combo tablets) May reduce risk of cancer Contraindicated with renal insufficiency or significant heart failure Kahn et al., NEJM 2006; 355: UKPDS Study Group, The Lancet1998; 352: Currie et al. Diabetologia. 2009;52:

5 ADA Review: Metformin Dosing with Chronic Kidney Disease (CKD) egfr Level (ml/min/1.73m 2 ) CKD Stage Action 60 1 or 2 No renal contraindication to metformin Monitor renal function annually A Continue use of metformin Monitor renal function every 3-6 months B Prescribe metformin with caution and use lower dose (e.g. 50% or half maximal dose); closely monitor renal function every 3 months Do not start patients on metformin <30 4 or 5 Stop metformin Additional caution is required in patients at risk for acute kidney injury or with anticipated significant fluctuations in renal status, based on previous history, other comorbidities, or potentially interacting medications

6 Overview of Noninsulin Therapies in Older Type 2 Diabetes Population Sulfonylurea (SUs) Class Advantages Disadvantages Comments DPP-4 Inhibitors glipitins Thiazolidinediones (TZDs) GLP-1 Receptor Agonists Effective Low cost Low hypoglycemia Well tolerated Can be used with renal impairment Effective Generic Low hypoglycemia Weight loss Effective Hypoglycemia Higher cost Joint pain Modest efficacy Edema, CHF, bone fracture Higher cost G.I. side effects Glipizide if renal impairment; avoid glyburide Reduce dose for renal impairment (except for linagliptin) Caution with, or at risk for, heart failure Once a week formulations available ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1, Package Inserts Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Mechanism of Action Inhibits renal re-absorption Selective inhibitor of SGLT2 -- acts in early proximal tubule to block reabsorption of filtered glucose Normally ~180 g glucose filtered/day Causes about 70 g (~300 kcal) glucose excretion per day; potential for weight loss Lumen Proximal Tubule Blood List et al. Diabetes Care, 2009; 32: ; Neumiller et al. Drugs, 2010; 70: Nair S. et al. J Clin Endocrinol Metab 2010;95:34-42 Copyright 2010 The Endocrine Society. X

7 Sodium-Glucose Cotransporter 2 (SGLT2) Canagliflozin (Invokana),Dapagliflozin (Farxiga), and Empagliflozin (Jardiance) Clinical Indicators Modest reduction in both FPG and PPG Approved as monotherapy, and in combination with metformin, SU, pioglitazone and/or insulin Modest weight loss, no additional hypoglycemia Precautions and contraindications Use caution with renal impairment (egfr <45-60) Symptomatic hypotension especially in elderly, renal impairment, patients treated with loop diuretics, ACE-I, and/or ARBs Dehydration and DKA (rare) Genital mycotic infections, especially in women or if history of mycotic infections Canagliflozin: Hyperkalemia (periodic monitoring if renal impairment and/or those on medications that impact potassium excretion) Package Insert Data Overview of SGLT2 Inhibitors Drug Dose egfr cutoff Comment Canagliflozin (Invokana) Dapagliflozin (Farxiga) 100/300 mg/day <45; use 100 mg if egfr Not recommended if severe hepatic impairment 5/10 mg/day <60 Avoid if history of bladder cancer Empagliflozin (Jardiance) 10/25 mg/day <45 Increased risk of volume depletion in pts. aged 75 yrs and older Package Insert

8 EMPA- REG Outcome: Time to First Occurrence of CV Death, Non-fatal MI or Non-fatal Stroke HR 0.86 (95.02% CI 0.74, 0.99) p=0.0382* Zinman et al. NEJM 2015 Number Needed to Treat to Prevent One Death in Landmark Trials in Patients with High CV Risk Simvastatin 1 for 5.4 years Ramipril 2 for 5 years Empagliflozin for 3 years High CV risk 5% diabetes, 26% hypertension Pre-statin era High CV risk 38% diabetes, 46% hypertension Pre-ACEi/ARB era <29% statin T2DM with high CV risk 92% hypertension >80% ACEi/ARB >75% statin S investigator. Lancet 1994; 344: HOPE investigator N Engl J Med 2000;342:

9 Priorities of Care for Older Adults with Diabetes Diagnosis Prevention Dx A1C 6.5%, fasting glucose 126 casual symptoms prevent pre-diabetes (IFG-IGT) & metabolic syndrome Self-Management Knowledge and Skill Monitoring Medication Problem solving Food plan & nutrition Risk reduction Living & coping Physical activity Glucose Lipids Hypertension Microvascular complications Other essentials of care B 2015 International Diabetes Center. ADA Hypertension Management Recommendations Systolic BP treatment target of <140 mmhg <150/90 for older, very complex patients in poor health Diastolic BP target <90 mmhg Consistent with JNC8 Treatment recommendations: Lifestyle changes including weight loss, DASH diet, reduced sodium, increased physical activity ACE inhibitor or ARB as first-line therapy Multiple medications often needed to achieve BP target, administer one or more at bedtime ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

10 Role of Intensive BP Control in Diabetes Results of the ACCORD BP Study mmhg 119 mmhg Average 3.4 antihypertensive medications in intensive vs. 2.2 in standard care Serious adverse events occurred 3.3% intensive vs. 1.3% standard care Evidence-base indicates <140 mmhg SBP is target. Or does it? ACCORD Study Group, N Engl J Med Systolic Blood Pressure Intervention (Sprint) Trial N=9361 >50 years with SBP >130 mmhg and high CV risk (no DM or stroke) SBP 140 mmhg vs 120 mmhg Chlorthalidione 1 st line, amlodipine, beta blockers More hypotension, syncope, acute renal injury/failure Stopped early due to lower rate of primary outcome Primary Outcome (MI, ACS, stroke, HF, and death due to CV cause) Years SPRINT Research Group, N Engl J Med

11 Other Sprint Trial Results of Importance for Older Patients 12% RRR in orthostatic hypotension in intensive treatment group No difference in injurious falls between groups Patients >75 years (28% total study population) benefited more than younger patients SPRINT Research Group, N Engl J Med Priorities of Care for Older Adults with Diabetes Diagnosis Prevention Dx A1C 6.5%, fasting glucose 126 casual symptoms prevent pre-diabetes (IFG-IGT) & metabolic syndrome Self-Management Knowledge and Skill Monitoring Medication Problem solving Food plan & nutrition Risk reduction Living & coping Physical activity Glucose Lipids Hypertension Microvascular complications Other essentials of care C 2015 International Diabetes Center.

12 ADA LDL Cholesterol Targets 2014 vs LDL-C Goal Diabetes LDL-C Goal Diabetes + CVD LDL-C Goal Diabetes LDL-C Goal Diabetes + CVD LDL-C <100 mg/dl LDL-C <70 mg/dl No target No target ADA Clinical Practice Recommendations, Diabetes Care 2014; 37 Suppl 1.; ADA Standards of Medical Care. Diab Care 2015; 38 Suppl ADA Dyslipidemia Management Recommendations Rationale Statin therapy benefits most diabetes patients No LDL targets, consistent with 2013 AHA/ACC recommendations ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

13 Intensity of Statin Therapy Statins associated with modest increased risk for diabetes (10-25%), yet CV benefit outweighs risk of diabetes Stone et al., Circulation. 2013; Nov Online. Ridker et al., Lancet. 2012;380: Stone et al, Circulation 2013: Published Online ADA 2015 Statin Therapy Recommendations Grade A Evidence Grade B Evidence ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

14 Primary Prevention in Diabetes Stone et al., Circulation. 2013; Nov Online. Stone et al, Circulation 2013: Published Online Combination Therapy for Dyslipidemia Rationale ACCORD trial showed the addition of fenofibrate to statin therapy did not reduce CV events compared to statin therapy alone AIM-High trial was stopped early due to lack of CV benefit of adding niacin to statin therapy vs. placebo ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

15 Statin & Fibrate Combination Therapy in Type 2 Diabetes Results of the ACCORD Lipid Study Addition of fibrate to statin increased HDL and decreased triglyceride modestly compared to placebo Trend towards benefit in patients with triglyceride 204 mg/dl and HDL 34 ACCORD Study Group, N Engl J Med Anti-platelet Agents in Diabetes Aspirin mg/day in type 1 and type 2 if 10 yr CHD risk >10% Men >50 yrs and Women >60 yrs with at least one additional risk factor Family history CVD, Hypertension, Smoking, Dyslipidemia, Albuminuria Combination with Clopidogrel for up to 1 yr post acute coronary syndrome Other Considerations Safe even if established retinal disease (ETDRS) Clopidogrel (Plavix) if aspirin contraindicated ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

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