¿Hacia dónde van los algoritmos de la ADA/EASD, AACE y ALAD en el tratamiento DM2. Control glucémico y protección cardiovascular como objetivo?
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Memorias Conferencia Científica Anual sobre Síndrome Metabólico 2017 - Programa Científico ¿Hacia dónde van los algoritmos de la ADA/EASD, AACE y ALAD en el tratamiento DM2. Control glucémico y protección cardiovascular como objetivo? Dr. Guillermo E. Umpiérrez Professor of Medicine in the Division of Endocrinology at Emory University School of Medicine, Section Head, Diabetes and Endocrinology. USA. Editor en Jefe del BJM Open Diabetes Research and Care.
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¿Hacia dónde van los algoritmos de la ADA/EASD, AACE y ALAD en el tratamiento DM2. Control glucémico y protección cardiovascular como objetivo?
- 1. Guillermo E. Umpierrez, MD, CDE, FACP, FACE Professor of Medicine Director Clinical Research, Diabetes & Metabolism Center Emory University School of Medicine Chief, Endocrinology Section, Grady Health System
- 2. External Industry Relationships * Company Name(s) Role Equity, stock, or options in biomedical industry companies or publishers BMJ Open Diabetes Research & Care AACE Editor-in-Chief Board of Directors Industry funds to Emory University for my research Merck, Sanofi, Novo Nordisk Boehringer Ingelhein Astra Zeneca Investigator-Initiated Research Projects Industry Advisory/Consultant activities Dr. Guillermo Umpierrez, Personal/Professional Financial Relationships with Industry February 2017 • ADA Professional Practice Recommendation Committee • AACE Diabetes Council and Guidelines Writing Committee • Chairman National AACE Primary care Diabetes Education
- 3. DIABETES MANAGEMENT GUIDELINES 1. Therapeutic options in T2DM 2. ADA-EASD Statements 3. AACE & Other Guidelines 4. Considerations in Choosing Drugs 5. A Look to the Future
- 6. Current Antihyperglycemic Medications Sulfonylureas Generalized insulin secretagogue 12 Groups with Different Mechanisms of Action -Glucosidase Inhibitors Delay CHO absorption Biguanide Reduces hepatic insulin resistance TZDs Reduce peripheral insulin resistance Amylin Analog Suppresses glucagon GLP-1 Analogs Stimulate b cells Suppress glucagon Colesevelam Bile acid sequestrant Bromocriptine Hypothalamic pituitary reset Insulin Replacement Therapy SGLT-2 Inhibitors Block renal glucose reabsorption Glinides Restore postprandial insulin patterns DPP-4 Inhibitors Restore GLP-1 Level
- 7. + - - peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple Complex Pathophysiological Abnormalities in T2DM renal glucose excretion
- 8. + - - peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 DA agonists T Z D sMetformin S U sGlinides DPP-4 inhibitors GLP-1R agonists A G I s Amylin mimetics Insulin Bile acid sequestrants Multiple Pathophysiologically-Based Therapies for T2DM renal glucose excretion SGLT-2 inhibitors
- 9. + - - peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 T Z D sMetformin DPP-4 inhibitors GLP-1R agonists S U s Insulin Major Pathophysiologically-Based Therapies for T2DM renal glucose excretion SGLT-2 inhibitors
- 10. Classes Generic Names A1c Side effects Insulin Degludec, Glargine, Detemir, NPH, Regular, Lispro, Aspart, Glulisine No limit Hypo, weight gain, injections SU’s Glyburide, Glipizide, Glimepiride 1-1.5% Hypo, weight gain Metformin Metformin 1-1.5% GI, lactic acidosis, B-12 deficiency TZD’s Rosiglitazone, Pioglitazone 1-1.5% Weight gain, edema, HF, bone fx’s, ?bladder ca DPP-4 i’s Sitagliptin, Saxagliptin, Alogliptin, Linagliptin 0.5-1% Urticaria, ?pancreatitis GLP-1 RA’s Exenatide, Liraglutide, Albiglutide, Dulaglutide, Lixisenatide 1-1.5% GI, ?pancreatic disease, injections SGLT2-i’s Canagliflozin, Dapagliflozin, Empagliflozin 0.5-1% Polyuria, GU infections, DKA, ?bone fxs
- 11. Classes Generic Names A1c Costs Insulin Degludec, Glargine, Detemir, NPH, Regular, Lispro, Aspart, Glulisine No limit variable SU’s Glyburide, Glipizide, Glimepiride 1-1.5% $ Metformin Metformin 1-1.5% $ TZD’s Rosiglitazone, Pioglitazone 1-1.5% $ - $$$ DPP-4 i’s Sitagliptin, Saxagliptin, Alogliptin, Linagliptin 0.5-1% $$$$ GLP-1 RA’s Exenatide, Liraglutide, Albiglutide, Dulaglutide, Lixisenatide 1-1.5% $$$$ SGLT2-i’s Canagliflozin, Dapagliflozin, Empagliflozin 0.5-1% $$$$
- 13. DIABETES MANAGEMENT GUIDELINES 1. Therapeutic options in T2DM 2. ADA-EASD Statements 3. AACE & Other Guidelines 4. Considerations in Choosing Drugs 5. A Look to the Future
- 14. ADA - EASD Consensus Statement (2008) Nathan DM, et al. Diabetes Care. 2008;31:1 At Diagnosis: Lifestyle + Metformin Lifestyle + Metformin + Sulfonylureaa Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + Intensive Insulin Lifestyle + Metformin + Pioglitazone Lifestyle + Metformin + GLP-1 agonistb Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + Pioglitazone + Sulfonylureaa STEP 1 STEP 2 STEP 3 Tier 2: Less well-validated therapies Tier 1: Well-validated therapies Reinforce lifestyle changes at every visit and check A1C every 3 months until < 7.0%, then at least every 6 months thereafter. Change interventions whenever A1C ≥ 7.0%. aSulfonylureas other than glibenclamide (glyburide) or chlorpropamide. bInsufficient clinical use to be confident regarding safety.
- 15. 2012 ADA-EASD ‘Position Statement’: Management of Hyperglycemia in T2DM: A Patient-Centered Approach GLUCOSE-LOWERING THERAPY • Glycemic targets - HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l]) - Pre-prandial PG <130 mg/dl (7.2 mmol/l) - Post-prandial PG <180 mg/dl (10.0 mmol/l) - Individualization is key: Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0%+) - older, comorbidities, hypoglycemia prone, etc. PG = plasma glucose Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596 • Pharmacological options - Individualize drug choice - Minimize adverse effects, especially hypoglycemia - Patient-centered care
- 16. Figure 1 Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596
- 17. Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596 2012 ADA-EASD Position Statement
- 18. 2012 ADA-EASD Position Statement
- 20. more stringent less stringent Patient attitude and expected treatment efforts highly motivated, adherent, excellent self-care capacities less motivated, non-adherent, poor self-care capacities Risks potentially associated with hypoglycemia and other drug adverse effects low high Disease duration newly diagnosed long-standing Life expectancy long short Important comorbidities absent severefew / mild Established vascular complications absent severefew / mild Readily available limited Usually not modifiable Potentially modifiable HbA1c 7% PATIENT / DISEASE FEATURES Approach to the management of hyperglycemia Resources and support system Diabetes Care 2015;38:140-49; Diabetologia 2015 58:429-42 Figure 1. Modulating intensive- ness of A1c lowering in T2DM
- 21. Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema,HF,fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + 2015ADA-EASD PositionStatement onManagementof Hyperglycemiain T2DM Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
- 22. Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema,HF,fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442 HbA1c ≥9% Metformin intolerance or contraindication Uncontrolled hyperglycemia (catabolic features, BG ≥300-350 mg/dl, HbA1c ≥10-12%)
- 23. AMERICAN DIABETES ASSOCIATION Standards of Medical Care in Diabetes - 2017 Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2017;40:S66 In patients with long-standing suboptimally controlled type 2 diabetes and established atherosclerotic cardiovascular disease, empagliflozin or liraglutide should be considered as they have been shown to reduce cardiovascular and all-cause mortality when added to standard care. Ongoing studies are investigating the cardiovascular benefits of other agents in these drug classes. B
- 25. HbA1c Weight Exenatide therapy: • Less nocturnal hypoglycemia • Higher patient-satisfaction • Increased risk GI side effects
- 26. DIABETES MANAGEMENT GUIDELINES 1. Pathophysiologically based therapeutic options in T2DM 2. ADA-EASD Statements 3. AACE & Other Guidelines 4. Considerations in Choosing Drugs 5. A Look to the Future
- 29. DM GUIDELINES: ADA-EASD vs. AACE ADA-EASD AACE Focus Glycemia Comprehensive (CV risk, weight, preDM) Gen’l A1c target <7.0% <6.5% Monotherapy metformin various Combination tx @ A1c 9.0% @ A1c 7.5% Therapeutic choices More narrow More broad Updates Every 3 years Annual
- 31. Algorithm for blood glucose lowering therapy in adults with type 2 diabetes
- 32. Oral Pharmacologic Treatment of T2DM: A Clinical Practice Guideline Update from the American College of Physicians Qaseem A et al. Ann Intern Med 2017 [Epub ahead of print 3 January 2017] doi: 10.7326/M16-1860 …monotherapy with metformin… …add a second agent… …add orals when lifestyle (has) failed…1 2 3
- 33. ALAD: Asociacion LatinoAmericana de Diabetes Glucose < 240 mg/dl and/or HbA1c < 8% Guzman et al. Rev Panam Salud Publica. 2010 Dec 28 (6) 463-71
- 34. ALAD: Asociacion LatinoAmericana de Diabetes Glucose < 240 mg/dl and/or HbA1c < 8% Guzman et al. Rev Panam Salud Publica. 2010 Dec 28 (6) 463-71
- 35. DIABETES MANAGEMENT GUIDELINES 1. Pathophysiologically based therapeutic options in T2DM 2. ADA-EASD Statements 3. AACE & Other Guidelines 4. Considerations in Choosing Drugs 5. A Look to the Future
- 36. 6 P’s of Personalizing of Diabetes Care 1. Pathophysiology Insulin resistance vs. deficiency? Stage of disease? 2. Potency Distance from A1c target? 3. Precautions Side effects, contraindications? (GI, renal, CV) 4. Pluses Added benefits beyond glucose control? (weight, BP, CV events) 5. Practicalities Pills vs. injections? Frequency? Need for BG monitoring? 6. Price Branded vs. generic? Formulary coverage?
- 37. www.GoodRx.com/, accessed June 18, 2016, (lowest price for New Haven, CT 06510) $0 $100 $200 $300 $400 $500 $600 $700 Liraglutide 1.8mg QD Canagliflozin 300mg QD Glargine 50U QD (pen) Sitagliptin 100mg QD NPH 50U QD (vials) Pioglitazone 45mg QD Glipizide 10mg BID Metformin 1000mg QD Cost for 30 days of therapy $4. $733. 183 X (!)
- 38. JAMA July 4, 2017 Volume 318, Number 1
- 39. DIABETES MANAGEMENT GUIDELINES 1. Pathophysiologically based therapeutic options in T2DM 2. ADA-EASD Statements 3. AACE & Other Guidelines 4. Considerations in Choosing Drugs 5. A Look to the Future
- 40. EFFICACY Lowering HgA1c SAFETY Hypoglycemia Prevention Management of Type 2 Diabetes Cardiovascular Disease Protection
- 41. Under Consideration: AMERICAN DIABETES ASSOCIATION Standards of Medical Care in Diabetes - 2018
- 44. Recommendations to prevent or delay the development of overt heart failure or prevent death before the onset of symptoms 2016 ESC Guidelines for the Diagnosis & Treatment of Acute & Chronic Heart Failure Ponikowski P et al. Eur Heart J 2016;37, 2129–200
- 45. CONFIDENTIAL 2008 2020 EXSCEL (exenatida) LEADER (liraglutida) REWIND (dulaglutida) ELIXA (lixisenatida) 2014 SUSTAIN-6 (semaglutida) 2010 2012 2016 CANVAS (canagliflozina) DECLARE (dapagliflozina) EMPA-Reg(empagliflozian) 2018 GLP1 Receptor Agonists SGLT-2 Inhibitors ORIGIN (glargina) Long Acting Insulin EXAMINE (alogliptina) CAROLINA (linagliptina) TECOS (sitagliptina) SAVOR (saxagliptina) DPP-4 Inhibitors 450 Reported Not-Reported Cardiovascular Safety Studies
- 46. • 9,340 T2D patients with high CVD risk • Mean age 64 yrs, A1c 8.7%, BMI 32.5 • Randomized to liraglutide 1.8mg or placebo (double blind)
- 47. N Engl J Med 2016;375:311-322. Placebo Liraglutide Modest A1c reduction compared to placebo
- 48. LEADER trial: Primary Outcome 15 10 20 5 0 0 6 12 18 24 30 36 42 48 54 Placebo Liraglutide Patientswithanevent(%) Months since randomisation Hazard ratio, 0.87 (95% CI, 0.78–0.97) P<0.001 for noninferiority P=0.01 for superiority First occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke in the time-to- event analysis in patients with type 2 diabetes and high CV risk. Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial Adapted from: Marso SP et al., NEJM 2016
- 49. LEADER trial: Death from Cardiovascular Causes 15 10 20 5 0 0 6 12 18 24 30 36 42 48 54 Placebo Liraglutide Patientswithanevent(%) Months since randomisation Hazard ratio, 0.78 (95% CI, 0.66–0.93) P=0.007 Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial Adapted from: Marso SP et al., NEJM 2016 CV death reduced by 22%
- 50. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes Marzo et al. NEJM 375;1874-88, 2016 The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
- 51. N Engl J Med 2015;373:2117-2128. • 7,020 T2D patients with CVD • Mean age 63 yrs, A1c ~8%, BMI ~31 • Randomized to empagliflozin 10mg, 25mg, or placebo (double blind) Primary outcome: Composite of death from cardiovascular causes, nonfatal MI, nonfatal CVA
- 52. EMPA-REG TRIAL • Study medication was given in addition to standard of care – Glucose-lowering therapy was to remain unchanged for first 12 weeks • Treatment assignment double masked • The trial was to continue until at least 691 patients experienced an adjudicated primary outcome event Randomised and treated (n=7020) Empagliflozin 10 mg (n=2345) Empagliflozin 25 mg (n=2342) Placebo (n=2333) Screening (n=11531) Zinman, B et al. NEJM 2015;373:2117-28.
- 53. Placebo Empagliflozin Modest A1c reduction with EMPA 29% of placebo, 23% of EMPA discontinued tx prematurely N Engl J Med 2015;373:2117-2128.
- 54. EMPA-REG Primary outcome: 3-point MACE (CV death, MI, stroke) Cumulative incidence function. MACE, Major Adverse Cardiovascular Event; HR, hazard ratio. * Two-sided tests for superiority were conducted (statistical significance was indicated if p≤0.0498) Zinman, B et al. NEJM 2015;373:2117-28.
- 55. EMPA-REG Cardiovascular Death Cumulative incidence function. HR, hazard ratio Zinman, B et al. NEJM 2015;373:2117-28.
- 56. HF Hospitalization reduced by 35% Placebo Empagliflozin N Engl J Med 2015;373:2117-2128.
- 57. CANVAS: CANagliflozin cardioVascular Assessment Study • T2DM ~14 years – Study medication in addition to standard of care – HbA1c ≥7.0% to ≤10.5% • High CV risk – eGFR ≥30 mL/min/1.73 m2 – Age ≥30 years and history of prior CV event – Age ≥50 years with ≥2 CV risk factors Zinman, B et al. NEJM 2017.
- 58. CANVAS n = 4330 2010 2011 2012 2013 2014 2015 2016 20172009 UL 95% CI <1.8 2010 2011 2012 2013 2014 2015 2016 20172009 UL 95% CI <1.3CANVAS trial starts CANVAS-R n = 5812 CANVAS: CANagliflozin cardioVascular Assessment Study Evaluate CV safetyCV safety proved and marketing authorization achieved CANVAS Program N = 10,142 Zinman, B et al. NEJM 2017.
- 59. Primary MACE Outcome CV Death, Nonfatal Myocardial Infarction or Nonfatal Stroke Years since randomization 2 3 4 5 61 Hazard ratio 0.86 (95% CI, 0.75-0.97) p <0.0001 for noninferiority p = 0.0158 for superiority 20 18 16 14 12 10 8 6 4 2 0 0 Patientswithanevent(%) Placebo Canagliflozin CANVAS: CANagliflozin cardioVascular Assessment Study Zinman, B et al. NEJM 2017.
- 60. Progression of Albuminuria 3819 3096 1690 724 626 548 303 5196 4475 2968 1730 1528 1354 775 Hazard ratio 0.73 (95% CI, 0.67-0.79) 2 3 4 5 60 1 100 90 80 70 60 50 40 30 20 10 0 Intent-to-treat analysis No. of patients Placebo Canagliflozin Years since randomization Patientswithanevent(%) Placebo Canagliflozin
- 61. Hazard ratio (95% CI) 1.00.5 2.0 Favors PlaceboFavors SGLT2i Nonfatal myocardial infarction Progression to macroalbuminuria* Renal composite* Hospitalization for heart failure CV death, nonfatal myocardial infarction, or nonfatal stroke CV death Nonfatal stroke Key Outcomes in the CANVAS Program and EMPA-REG OUTCOME *CANVAS Program endpoints comparable with EMPA-REG OUTCOME. 0.25 Zinman Bet al. N Engl J Med. 2015 ;373(22):2117-2128. Wanner K et al. N Engl J Med. 2016;375(4):323-334. CANVAS Program EMPA-REG OUTCOME CV death or hospitalization for heart failure All-cause mortality
- 62. Management of Type 2 Diabetes SU TZD DPP4 SGLT2 GLP1 Insulin Efficacy ++ ++ + ++ ++ ++ Safety + + + + CV Protection - + ++ ++ EFFICACY Lowering HgA1c SAFETY Hypoglycemia Prevention CVD Protection
- 63. Study SAVOR EXAMINE TECOS CAROLINA CARMELINA DPP4-i saxagliptin alogliptin sitagliptin linagliptin linagliptin Comparator placebo placebo placebo sulfonylurea placebo N 16,500 5,400 14,000 6,000 8,300 Results 2013 2013 2015 2017 2017 Study LEADER ELIXA SUSTAIN 6 EXSCEL REWIND GLP1-RA liraglutide lixisenatide semaglutide exenatide LR dulaglutide Comparator placebo placebo placebo placebo placebo N 16,500 14,000 6,000 5,400 8,300 Results 2016 2015 2016 2018 2019 Study EMPA-REG CANVAS DECLARE NCT01986881 SGLT-2-i empaglifozin canagliflozin dapagliflozin ertugliflozin Comparator placebo placebo placebo placebo N 7300 4300 22,200 3900 Results 2015 2017 2019 2020 Large CV Outcomes Trials in Diabetes (Non-Insulin)
- 64. 1. Increasing T2DM prevalance & complexity of therapeutic options have led to the need for treatment “guidelines.” 2. Most begin quite similarly (“Lifestyle…then metformin…”), but differ to varying degrees on what to do next. 3. Emerging data from recent CVOT trials should lead to some modifications in guidelines - particularly in those patients with overt CVD. 4. There will also always be a need for the wise and skilled physician to choose the optimal therapeutic regimen for (and with) each patient.
- 65. Muchas Gracias