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Diabetes Mellitus 101 for Cardiologists (and Alike): 2015

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 13. Stan Schwartz MD,FACP Affiliate, Main Line Health System

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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 13 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000

  2. Insulin Secretagogues: Sulfonylureas and “Glinides” • Safety and Efficacy -Decreases HbA1c approx1–2%(sfu, repaglinide)(0.5-1.0%,neteglanide) -Adverse events: Wt gain, sulfa allergy (sfu,rare), -cell apoptosis (sfu) Main risk = hypoglycemia , inc ischemia risk(~50% less w/repaglinide,75% less with neteglanide) Increase Cancer vs Metformin Abnormal ischemia pre-conditioning SO WHY USE SOMETHING THAT DESTROYS BETA-CELLS THAT YOU’D LIKE TO SAVE Davies MJ. Curr Med Res Opin. 2002;18(Suppl 1):s22-30.

  3. Sulfonylureas and Ischemic Pre-conditioning

  4. Meta-Analysis: Cardiovascular Risk With Sulfonylurea Plus Metformin Relative Risk (95% CI) Bruno (1999) Olsson (2000) Johnson (2005) Koro (2005) Evans (2006) (A) Evans (2006) (B) Evans (2006) (C) Overall 1.04 (0.62-1.75) 1.86 (1.33-2.61) 0.96 (0.82-1.12) 1.38 (1.13-1.69) 2.24 (1.26-3.99) 1.86 (1.03-3.35) 1.52 (0.84-2.76) 1.43 (1.10-1.85) 0.25 1.0 4.0 Results With Combination Therapy • Increased composite cardiovascular risk end point (RR 1.43; 95% CI, 1.10-1.85) • All-cause mortality alone – not significant • Cardiovascular disease mortality alone – not significant Composite end point: cardiovascular hospitalization or mortality Relative risk: combination therapy vs. diet, metformin alone, or sulfonylurea alone Rao AD, et al. Diabetes Care. 2008;31:1672-1678. RR = relative risk

  5. Higher Mortality Is Associated With Greater Exposure to Sulfonylurea Monotherapy group Monotherapy group Deaths/1000 person-years Deaths/1000 person-years Hazard ratio Hazard ratio Adherence Daily Dose Poor (good) 1.55 1.34 1.33 49.0 (75.8) Glyburide (n = 4138) 1.10 1.09 0.98 Lower (higher) 1.32 1.29 1.29 37.7 (41.3) Metformin (n = 1537) 53.4 (70.2) Glyburide (n = 4138) 0 1 2 0.92 0.96 0.84 41.5 (37.6) Metformin (n = 1537) Unadjusted Adjusted for age, sex, chronic disease score (CDS), and nitrate use Adjusted for age, sex, CDS, nitrate use, physician visits, and hospital admissions 0 1 2 There was a greater risk of death associated with higher daily doses and better adherence for patients who used glyburide (HR = 1.3; 95% CI, 1.2-1.4), but not metformin (HR = 0.8; 95% CI, 0.7-1.1) A retrospective, inception cohort study conducted in 5795 new users of oral glucose-lowering medications - Insulin or combination therapy were excluded - Mean age: 66.3 years - Mean follow-up: 4.6 years - Main outcomes: all-cause mortality, death from acute ischemic event Simpson SH, et al. CMAJ. 2006;174:169-174.

  6. MUST CONSIDER TOTAL COST- Incretin vs Sulfonylureas- not per/pill • ER Visits • Hospitalizations • Mortality • Under-recognized- hypoglycemic unawareness • Lifestyle Restrictions, diminished quality of life • Worry for Spouse, Friends, Co-workers • Fear of Hypoglycemic leads to inadequate Control • Severe Hypoglycemia Raises the Risk of Dementia • Increased cost of increased number SMBG testing And 2 Part-D insurers now ask for prior auth for GLYBURIDE, ? SUs And Given Apoptosis, death of beta-cells with SU, you’ll need expensive drugs anyway in 1-3 years- but now at disadvantage of having lost b-cell mass

  7. Decrease b-cell demand- - dec CV outcomes, STOP- NIDDM • Decrease HbA1c 0.5–1% • Decrease PPG,TG • Delay DM Adverse events: flatulence,treat hypoglycemia with glucose

  8. Other Meds with ‘synergistic’ Glycemic and CV Benefit Colsevelam lipid benefit (Ranolazine) Decrease angina ( or equivalent) Decreases arrhythmia Improves diastolic dysfunction, thus-decreases edema of Pio-, Decreases HgA1c, FBS in glucose dependent fashion , no hypoglycemia

  9. Colsevelam in Prediabetes Handelsman

  10. Other Meds with ‘synergistic’ Glycemic and CV Benefit Colsevelam lipid benefit (Ranolazine) Decrease angina ( or equivalent) Decreases arrhythmia Improves diastolic dysfunction, thus-decreases edema of Pio-, Decreases HgA1c, FBS in glucose dependent fashion , no hypoglycemia

  11. P l a c e b o CHANGE FROM BASELINE IN HbA1c IN DIABETIC PATIENTS M o n t h s o f F o l l o w U p 4 8 0 R a n o l a z i n e - 0 . 2 N=770 N=535 Change in HbA1c (%) - 0 . 4 P<0.001 - 0 . 6 P<0.001 - 0 . 8 Modified from: Morrow et al. Circulation Suppl. 2008 (Abstract)

  12. p = 0 . 0 0 2 8 p < 0 . 0 0 0 1 CARISA: DOSE DEPENDENT EFFECT OF RANOLAZINE ON HbA1c AFTER 12 WEEKS n=47 n=47 0 n=37 - 0 . 5 HbA1c (%) (change from baseline) - 1 . 0 - 1 . 5 0 7 5 0 m g 1 0 0 0 m g R a n o l a z i n e Chisholm and Belardinelli (2008). CVT unpubl data

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