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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

This article provides a comprehensive overview of an aggressive pathophysiological approach to the therapy of type 2 diabetes in cardiometabolic patients. It discusses the use of diabetes medications from a cardiologists' perspective and emphasizes the importance of combination therapy to address multiple etiologies of hyperglycemia. The article also highlights the need to match drug characteristics with patient characteristics and provides recommendations based on A1C levels. Overall, the article aims to provide guidance on selecting the right drugs for the right patients to achieve optimal glycemic control and reduce complications.

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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

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  1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: Looking at Diabetes Medications with a Cardiologists Eye Part 16 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000

  2. New ADA Guidelines- 4/20/12 SU Still Prominent But Incretins including DPP-4s on list Inzucchi, Diabetes Care 2012;35:1364 Inzucchi, Diabetologia 4/20/12

  3. Strongly disagree with less stringent Advice- ie: I would be as aggressive in care as other Patients, as long as don’t use agents that cause weight gain or hypoglycemia Figure 1 Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print] (Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)

  4. AACE/ACE:Recommendations Based on A1C at Diagnosis/ or When you see in OfficeEMPHASIS on Using Combination Therapy to ADDRESS multiple etiologies of hyperglycemia in Octet Lifestyle Modifications Monotherapy Dual therapy Triple therapy A1C 6.5%-7.5% A1C 7.6%-9.0% A1C >9.0% If under treatment If drug naive Symptoms No symptoms Dual therapy Insulin plus other agent(s)* Insulin plus other agent(s)* Triple therapy Triple therapy Use Sulfonylureas/Glinides LAST, IF AT ALL Therapeutic Choice, based on Safety/ Efficacy, Should Match The Drug Characteristics With Patient Characteristics Rodbard HW, et al. Endocr Pract. 2009;15:540-559.

  5. Follow current AACE GUIDELINE PRINCIPLES • Treat as many of the Ominous Octet Targets as needed, with least # of agents, to get lowest sugars/HgA1c as possible without undue weight gain or hypoglycemia • Early Combination Therapy First Tier- Efficacy, (my add- CV event reduction, Weight Loss) • Treat with agents thataddress FBS AND PPG • Ideally agents will stabilize, preserve beta-cells , the CORE DEFECT ( NO SU/GLINIDES) • Ideally agents will have potential to synergistically decrease in CV risk factors/ outcomes

  6. Initial Triple Combination Therapy is Superior to ADA Guide 147 newly diagnosed T2DM (age = 45±1; BMI=36±0.5; A1c = 8.6±0.1%; diabetes duration = 5.6±0.5mo) were randomized to receive Results: Triple Therapy, A1c 8.6 to 6.1% at 6 mo and remained stable at 6.1% at 24 Conventional Therapy, 6.1% at 6 mo and then increased to 6.6% at 24 mo (p < 0.01).More subjects in Conventional Arm failed to achieve the treatment A1c goal <6.5% (46 vs 22%, p<0.0001)., Triple Therapy subjects had a 13.6-fold lower rate of hypoglycemia compared to subjects receiving Conventional Therapy. Triple Therapy subjects had mean weight loss of 1.2 kg versus 3.6 kg weight gain (p=0.02) in subjects on Conventional Therapy.

  7. First Tier/ Second Tier AACE Meds • First Tier- drop HgA1c 1-2% • Metformin, pioglitazone , GLP-1 RA • Second Tier • SGLT-2 inh. • DPP-4 Inh, ranolazine, • bromocriptine-QR, colsevalam, alpha-glucosidaseinh.

  8. Uses Across Continuum of Care 1. Pre-Diabetes 2. Rest of Continuum of Care 3. AACE Guidelines, Triple RX before Insulin Pick Right Drug for Right Patient 4. Delay Need for Insulin No need for Early Insulin 5. If need Insulin, Continue Non-Insulin RX Avoids need for Meal-Time Insulin Decrease Risk Hypoglycemia 85% 6. Get Patients off insulin Had been given Early Insulin

  9. Concurrent Therapy

  10. Aggressive medical therapy in diabetes ACE inhibitorsARBs β-blockersCCBsDiuretics Hypertension Atherosclerosis StatinsFibric acid derivatives Colsevalam Dyslipidemia MetforminTZDsSulfonylureas/GlinideRANOLAZINE colsevalam Incretins Insulin Hyperglycemia/ Insulin resistance ASAClopidogrelTiclopidine Platelet activationand aggregation Adapted from Beckman JA et al. JAMA. 2002;287:2570-81.

  11. Treating the ABCs Reduces Diabetic Complications 1 UKPDS Study Group (UKPDS 33). Lancet. 1998;352:837-853. 2 Hansson L, et al. Lancet. 1998;351:1755-1762. 3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:703-713. 4 Grover SA, et al. Circulation. 2000;102:722-727. 5 Pyŏrälä K, et al. Diabetes Care. 1997;20:614-620.

  12. Synergies In Therapy for the Cardiometabolic Syndrome ?√ ?√

  13. Summary Treat aggressively-benefit on cost and complications Treat elements of pathophysiology Resistance-glycemia,endothelial dysfunction,lipids,BP,coag. Secretion-first phase,incretin,importance of PPG Multi-hormonal issues Use SIDE-BENEFITS of the various agents Treat to new goals using combinations that make pathophysiologic sense Guidelines should help pick right drug(s) for right patients

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