Extending The Healthspan Of Those With Diabetes And Prediabetes Anne Peters, MD Professor, USC Keck School of Medicine Director, USC Clinical Diabetes Programs
Disclosure Advisory Boards Research Funding • Abbott Diabetes Care • Dexcom • Astra Zeneca • Mannkind • Bigfoot Biomedical • BD, BI • Lexicon, Lilly, Livongo • Medscape, Merck • NovoNordisk (also Speaker’s Bureau) • Omada Health • Sanofi, Science37
Objectives 1. Review burden of diabetes 2. Discuss diabetes prevention in 2018 3. Analyze CVOT outcome data in T2DM 4. Look at outcomes beyond A1C
Years of Life Lost Due to Diabetes by Age of Onset Age at Diabetes Onset Narayan et al JAMA 2003;290:1884-1890
Complications in T2D and the Metabolic Syndrome Hyperglycemia Hypertension Dyslipidemia Insulin Resistance 6 Macrovascular To General Population Disease 5 Risk Relative 4 3 2 Diabetic 1 Retinopathy 0 -20 -15 -10 -5 0 5 10 15 20 Years of Diabetes Adapted from: Kendall DM. Am J Manag Car e 7S327-S343, 2001.
Diabetes Prevention Program: Incidence of T2D 40 Placebo Cumulative incidence 30 28.9% of diabetes (%) Metformin 21.7% 20 Lifestyle 14.4% 10 0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 P <0.001 for each comparison. Years N = 3324 Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.
Medicare Diabetes Prevention Program https://innovation.cms.gov/initiatives/medicare-diabetes-prevention- program/
LDL Cholesterol Targets in Diabetes 4S LIPID CARE Post CABG Clinical Event Rate ASCOT HPS Risk Attributable CARDS to LDL-C PROVE IT Residual Risk of CVD ? Role of other lipid and non-lipid factors 60 80 100 120 140 160 180 200 220 LDL Cholesterol (mg/dl)
Severe Hypoglycemia and Mortality Risk ACCORD ADVANCE VADT Severe Hypo Intensive Standard Intensive Standard Intensive Standard (%/ year) 3.1% 1.1% 0.7% 0.4% 12.0% 4.0% Annual mortality 5.0% 4.9% 4.0% Yellow = 2.8% 3.0% +severe hypo 2.0% 1.0% 1.3% 1.0% 0.0% Intensive Standard Bonds et al. BMJ 2010;340:b4909
CV Outcomes Trials in Diabetes: DPP-IV I Study SAVOR EXAMINE TECOS CAROLINA CARMELINA DPP4-I saxagliptin alogliptin sitagliptin linagliptin linagliptin Comparator placebo placebo placebo SU placebo N 16,492 5,380 14,735 6,072 7,003 Reported 2013 2013 2015 2018 2018 CVOT Neutral Neutral Neutral Outcome Other Increased Increased CHF CHF • CHF warning on all DPP-IV I’s in patients at risk for heart failure N Engl J Med 2013; 369:1317-1326 N Engl J Med 2013; 369:1327-1335 N Engl J Med 2015; 373:232-242
CV Outcomes Trials in Diabetes: GLP1-RA Study ELIXA FREEDOM LEADER SUSTAIN 6 EXSCEL -CVO GLP1-RA lixisenatide ITCA-650 liraglutide semaglutide exenatide LR exenatide N 6068 ~4,000 9,340 3,297 14,752 Reported 2015 2016 2016 2016 2017 CVOT Neutral Neutral Benefit Benefit Neutral In label Outcome Other Renal Worsening benefit retinopathy Ongoing = REWIND Dulaglutide n = 9901 N Engl J Med 2016; 375:1834-1844, N Engl J Med 2016;375:311-322, Diab Obes Metab 2018;20:42-49, N Engl J Med 2017;377:1228-1239, NEJM 2015;373:2247-2257
Primary outcome CV death, non-fatal myocardial infarction, or non-fatal stroke The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio. Presented at the American Diabetes Association 76 th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
CV death The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio. Presented at the American Diabetes Association 76 th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
Hospitalization for heart failure The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional- hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; HR: hazard ratio. Presented at the American Diabetes Association 76 th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
Time to first renal event Macroalbuminuria, doubling of serum creatinine, ESRD, renal death The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional- hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; ESRD: end-stage renal disease; HR: hazard ratio. Presented at the American Diabetes Association 76 th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
CV Outcomes Trials in Diabetes: SGLT-2 I Study EMPA-REG CANVAS DECLARE- VERTIS-CV Program TIMI SGLT-2 I empagliflozin canagliflozin dapagliflozin ertugliflozin N 7028 10,142 17,276 ~8,000 Reported 2015 2017 2018 2019 CVOT Benefit Benefit Pending Pending In label Outcome Other Reduction in Increased risk CHF of amputation Renal Benefit and fracture N Engl J Med 2015; 373:2117-2128, N Engl J Med 2017; 377:644-657,
EMPA-REG CV death HR 0.62 (95% CI 0.49, 0.77) p <0.0001 N Engl J Med 2015; 373:2117-2128
EMPA-REG Heart Failure Hospitalization HR 0.65 (95% CI 0.50, 0.85) p =0.0017 N Engl J Med 2015; 373:2117-2128
EMPA-REG Renal Function over Time Wanner C et al. N Engl J Med 2016;375:323-334
The Many Paths to an A1C = 7% Brown A, Close K. Close Concerns FDA briefing
T1DM: A1C =6.8%, low variability 180 80
T1DM: A1C = 6.9%, high variability
Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes A Consensus Statement of AACE, AADE, ADA, Endo Society, JDRF International, Helmsley Charitable Trust, Pediatric Endo Soc and the T1D Exchange
Hypoglycemia Level Definition Level 1 Glucose <70 mg/dl (3.9 mmol/L) and >54 mg/dl (3.0 mmol/L) Level 2 Glucose <54 mg/dl (3.0 mmol/L) Level 3 A severe event characterized by altered mental and/or physical status requiring assistance American Diabetes Association Standards of Medical Care in Diabetes. Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
Hyperglycemia Level Definition Level 1 Glucose >180 mg/dl (10 mmol/L) and <250 mg/dl (13.9 mmol/L) Level 2 Glucose >250 mg/dl (13.9 mmol/L)
Time in Range/DKA Outcome Definition Time in Range Percentage of readings in the range of 70 mg/dl (3.9 mmol/L) - 180 mg/dl (10 mmol/L) per unit of time DKA • Elevated serum ketones (above ULN) and • Serum bicarbonate <15 mmol/L or blood pH <7.3
The Value of Continuous Glucose Monitoring
Flash Glucose Monitoring
Nondiabetes
Nondiabetes
Approaching Prediabetes
PreDiabetes
Almost Diabetes
A1C Over 7%
T2DM: On Metformin alone
“Normal” Fasting Blood Sugar Levels 150
“Normal” Fasting Blood Sugar Levels
“Do I Really Need Insulin?”
77 yo on metformin + nateglinide
77 yo on metformin + nateglinide + basal insulin
Knowledge ≠ Adherence: Middle Aged Pharmacist
Real World: Impact of Adherence Diabetes Care 2017 Aug 11. pii: dc162725. doi: 10.2337/dc16-2725. [Epub ahead of print]
JP—On SU/lira/empa/glargine/met, not working
JP on met/dula/degludec
T1DM: Twice daily NPH and Reg, ELA
Stepp-Up Project
ADA 2018: Treatment of Adults with T2DM Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018 . Diabetes Care 2018; 41 (Suppl. 1): S73-S85
ADA 2018: Treatment of Adults with T2DM Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018 . Diabetes Care 2018; 41 (Suppl. 1): S73-S85
Thank You
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