1. Diabetes Mellitus 101 for Cardiologists (and Alike): 2015 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000 An Aggressive Pathophysiologic Approach to Therapy of Type 2 Diabetes in Cardiometabolic Patients: Looking at Diabetes Medications with a Cardiologists Eye Part 8

2. Pioglitazone  ADVANTAGES-  Improves insulin resistance (fat/muscle), decreases insulin conc., improves endothelial dysfunction, dysfibrinolysis, BP, decreased microalbumin, improved beta-cell function, treats PCOS and steatohepatitis Lipids (GLIA study) Advantage to pio - decrease TG, decreased # of buoyant LDL particles, decrease non-HDL chol. May use in renal insufficiency  No hypoglycemia used alone or with metformin, incretin mimetics  Potential to delay or prevent DM and progression; lower secondary failure rate than SU/met  Pio decreased prospective composite endpoint (MI,CVA, death) 16% in PROactive trial (Can’t assume class effect), dec. risk second MI/ ACS, decreased risk second stroke 47%

3. Non-Insulin Therapy for Hyperglycemia in Type 2 Diabetes,Treating Defronzo’s Octet: Match Patient Characteristics to Drug Characteristics: PIOGLITAZONE improves 5 of 8 MOAs 5. Gut CHO Absorption: Incretin, Pramlintide, Glucosidase inh. Peripheral glucose uptake -- - 1.Pancreatic insulin Secretion: Incretin, ranolazine 2.Pancreatic glucagon Secretion- Incretin HYPERGLYCEMIA 6.Fat- TZD, metformin 7.Brain- TZD,INCRETIN, bromocryptine 8.Kidney- SGLT2 3. Muscle- TZD, Incretin 4.Liver Hepatic glucose production: Metformin, incretin De

4. Pioglitazone in Dysmetabolic Syndrome, Prediabetes, Type 2 Diabetes  Safety  No liver toxicity  Increased distal fractures in women  Edema-renal sodium and total body water retention - can be prevented/minimized (patient selection, NAS diet) - treated with spironolactone, amilioride, triamterene  Weight gain not an obligatory side effect- studies- portion control/ education freq.  Bone loss in women = risk/benefit evaluation for each patient  CHF not a cardiac issue except more susceptible with diastolic dysfunction –function of renal sodium and total body water retention -Can be prevented/reduced- low salt diet/ patient selection; ranolazine

12. © 2000 educateMD.com University of Pennsylvania School of Medicine Wang CH, et al. Glitazones and Heart Failure. Circulation. 2003;107:1350-1354. Reprinted with permission