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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 12. 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 12 Stan Schwartz MD,FACP Affiliate, Main Line Health System Emeritus, Clinical Associate Professor of Medicine, U of Pa. 6105472000

  2. Incretins in Natural History of DM Type 2- reduce bolus need Type 1- decrease variability, dawn, pumps Late-pp hypo, Prevention / Delay of DM AACE Guideline based Delay of 1st-phase Metabolic syndrome Pre-diabetes DM- non- insulin Rx Insulin need insulin release Weight reduction methods- GLP-1;Glp-1 before pio; GLP-1 before insulin Dpp-4/ GLP-1 RA Instead of SU/Glinide Get off Insulin Stress/ Steroid DM Even late in DM

  3. Renal Threshold SGLT-2 Inh. DM nml SGLT-2 Inhibitors DM NML 80 SGLT-2-INH.

  4. Thus the Logic for SGLT-2 Inhibition: we’ll discuss Benefit/ Risks My Own Comment on MOA- Logic for Benefit: • Kidney is an ‘active player’ in Hyperglycemia-- eg: • EARLY (in pre-diabetes) Up-regulation of SGLT-2 protein is a Mal-adaptive response to body perceiving lose of glucose as a risk for insufficient glucose for brain function • Lowering blood sugar by reducing tubular re-absorption of glucose treats THE Core defect in Diabetes- abnormal b-cell function, by decreasing glucotoxicity

  5. 40-50% efficient as hepatic glucose production increased, yielding up to 1% drops; Obviate with incretin Rx- Durable up to 1 year No hypoglycemia Reduce fluctuation Durable and effective across natural Hx DM

  6. SGLT-2 Inhibitors • Canagliflozin • Dapagliflozin • Empagliflozin Principles in our discussion: There are no head-to-head-trials: can’t compare numbers so emphasize commonality of efficacy/ safety/risk ; minor differences between these agents !

  7. General Observations Across Clinical Trials • No significant changes in plasma electrolytes • Slight increase in Hct and decreases in serum uric acid • CV • Improvement in triglycerides and HDL cholesterol • Slight increase in LDL cholesterol • Consistent decreases in SBP, DBP, and weight • Consistent increase in “genital infections” • Inconsistent increase in lower urinary tract infections • Volume depletion risk

  8. SGLT-2 Inhibitor Infection Risk: Principles Ferrannini E, et al. Diabetes Care. 2010;33(10):2217-2224. Increased incidence of urinary tract • more common if history of frequent UTI’s or colonized; • if get one, low risk recurrence • Rare pyelonephritis/ urosepsis Genital yeast infections : • more common if history of frequent UTI’s or colonized • If get 1, low risk of recurrence • In men, rare if circumcised; vast majority occurred in uncircumcised

  9. Side Effects SGLT-2 Inhibition cana cana cana Minimize by- push PO intake, fastidious bathroom habits; urinate after intercourse before sleep If baseline BP low- cut back or d/c diuretic or antihyperetensive Watch K+, if older, eGFR 45-60, on ACE / spironolactone

  10. Practical Clinical Approaches To Maximize Benefits and Minimize Risks • Initial Script • Check eGFR, BUN/Cr, K+, BP, recent sugar eGFR appropriate dosing lower doses for lower eGFR, older, on loop-diuretic; Advise push PO fluids, hold med with a GI flu, etc; note increased urination expected • Female- careful bathroom habits, urinate after intercourse before sleep • Male- especially uncircumsized- get tip of penis dry before leave bathroom • K+ high nml- adjust K=sparing diuretic,ACE/ARB decrease high K+ foods • Low BP- cut back/stop something- HCTZ, or BP med • Very High sugar- start other meds and NCS diet first, start SGLT-2 3 days later • 2 - 4 week visit- Re-inforce benefits they’ve seen; supports compliance – Check eGFR, BUN/Cr, K+, BP Treat yeast infections- clotrimazole topical/vaginal; diflucan 150 mg and repeat 2 days later

  11. Lowers Renal Glucose Threshold to 80 – Very EFFECTIVE, but…Should drop HgA1c more:Liver Compensates for increased glycosuria with increased hepatic glucose production

  12. Thus Logic for SGLT-2 Inhibitor with Incretins

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