3. Cardiovascular Disease?

Transcription

1 Swiss recommendations 2016 Swiss Society of Endocrinology and Diabetology 1. Deficiency? Basal Premixed- Basal + GLP-1 RA (Xultophy ) or Basal Bolus 2. egfr < 30 ml/min? 3. Cardiovascular Disease? 4. Heart Failure? yes no DPP-4 Inhibitors SGLT2 I. GLP-1 RA SGLT2 I. or SGLT2 I. GLP-1 RA or + DPP-4 I. Metformin + DPP-4 I. Basal + DPP-4 I. or Gliclazide or Basal + Gliclazide or Basal + Gliclazide or Basal Basal

2 Guidelines for Type 2 Diabetes: Keeping the Finger on the Pulse...Several national guidelines, including those from Canada and Switzerland, have also responded quickly to these new data. However, to our knowledge, NICE in the UK has not yet responded to this evidence, even though results from EMPA- REG OUTCOME were published 3 months before the most recent NICE guidance in 2015 (NG28)... Lancet Diabetes Endocrinol 2017 Anthony H Barnett, Paul O Hare, Julian Halcox Published Online April 19, S (17)

3 Overview of current T2D treatments Which Priorities? Class Rarely used medications not used in treatment recommendations (<5% market share = a-glucosidase inhibitors, Pioglitazone, Repaglinide) Priority according to treatment strategy Reduction cardiovascular complications Relative HbA 1c Lowering (Effectiveness) Reduced e-gfr ( <45/<30 mlmin) Hypoglycemia Risk Body Weight Application Metformin (long-term) + /- oral $ Costs SGLT-2 Inhibitors GLP-1 R Agonists DPP-4 Inhibitors (basal) Sulfonylurea - + /- oral $$ ( ) + /- Injection $$$ + /+ oral $$ + /+ Injection -/- oral $ $ - $$

4 Swiss Recommendations 2016 Priority: Reduction of cardiovascular disease Classes SGLT-2 Inhibitors GLP-1 R Agonists Reduction cardiovascular complications Relative HbA 1c Lowering (Effectiveness) Reduced e-gfr ( <45/<30 mlmin) Hypoglycemia Risk Body Weight Application Costs - + /- oral $$ ( ) + /- Injection $$$ Metformin (long-term) + /- oral $ DPP-4 Inhibitors (basal) Sulfonylurea + /+ oral $$ + /+ Injection -/- oral $ $ - $$

5 Swiss Recommendations 2016 Priority: No Hypoglycemia Classes Reduction cardiovascular complications Relative HbA 1c Lowering (Effectiveness) Reduced e-gfr ( <45/<30 mlmin) Hypoglycemia Risk Body Weight Application Metformin (long-term) + /- oral $ Costs SGLT-2 Inhibitors GLP-1 R Agonists DPP-4 Inhibitors (basal) Sulfonylurea - + /- oral $$ ( ) + /- Injection $$$ + /+ oral $$ + /+ Injection -/- oral $ $ - $$

6 Swiss Recommendations 2016 Priority: Costs Classes Reduction cardiovascular complications Relative HbA 1c Lowering (Effectiveness) Reduced e-gfr ( <45/<30 mlmin) Hypoglycemia Risk Body Weight Application Metformin (long-term) + /- oral $ Costs Sulfonylurea (basal) SGLT-2 Inhibitors DPP-4 Inhibitors GLP-1 R Agonists -/- oral $ + /+ Injection - + /- oral $$ + /+ oral $$ ( ) + /- Injection $$$ $ - $$

7 Swiss recommendations clinical questions 1. Deficiency? 2. egfr < 45/30 ml/min? 3. Cardiovascular Disease? 4. Heart Failure?

8 Question 1: Is there insulin deficiency? SGLT-2 Metformin GLP-1 Inhibitor o RA DPP-4 inhibitor Sulfonylurea Deficiency o o o o + o Symptomatic Hyperglycemia + Metabolic Decompensation Polyuria Polydipsia Weight Loss Volume Depletion 1. SSED/SGED guidelines update.

9 use in type 2 diabetes in Switzerland Increasing need for insulin with advancing kidney failure patients (mean age 66.5 ± 12.4 years) included by 109 primary care physicians need (27-50%) Swiss Med Wkly Feb 28;146:w14282

10 Diabetes Treatment with CKD in Switzerland CKD e-gfr <60 ml/min: 22.4% CKD 4+5: egfr < 30 ml/min? CKD 3b: egfr < 45 and >30 ml/min? CKD 3a: egfr < 60 and > 45 ml/min? 2.4 % of all patients 6.1 % of all patients 13.9 % of all patients DPP-4 Inhibitor Metformin (1/2 dose) +SGLT2-I. or GLP-1 RA Early combination Metformin +SGLT2-I. or GLP-1 RA Basal DPP-4 I. Basal- Swiss Med Wkly Feb 28;146:w14282 DPP-4 I. /Glicazide Basal-

11 Swiss recommendations 2016 Asymptomatic with high risk for cardiovascular event 3. Cardiovascular Disease? yes Predict Study (589 Patients (50-70 years old: T2D + no cardiovascular disease): Coronary Artery Calcium Score (CACS) Follow-up: 4 years; first CHD + stroke event BMI > 28 Relative Risk Percentage of population SGLT2 I. GLP-1 RA 1 4 ~25/50% of all patients with T2D >13 or 7 fold increased risk for CHD and stroke events % 51% 22% Eur Heart J. 2008;29(18): doi: /eurheartj/ehn279

12 Swiss recommendations 2016 Symptomatic cardiovasular disease? 1.9 Million Individuals > 30 years and free of cardiovascular disease Follow-up: 5.5 years 3. Cardiovascular Disease? SGLT2 I. yes BMI > 28 GLP-1 RA Endpoint: First occurence of cardiovascular disease event Type 2 Diabetes (n=34 198) 6137 events = 17.9% of population Most frequent: PAD 16.2% and heart failure 14.1% No Diabetes events = 5.7% of population Heart failure 12.1% and PAD: 9.2% Lancet Diabetes Endocrinol Feb; 3(2):

13 Cardiovascular disease in individuals without and with type 2 diabetes? 9.4% 12.2% 11.4% 14.1% 9.4% 9.3% 10.2% 5.2% 4.7% 4.9% 3.0% 2.1% 2.8% 1.2% Lancet Diabetes Endocrinol Feb; 3(2): % peripheral arterial disease 14.1% heart failure 11.9% stable angina 11.5% non-fatal MI 10.3% stroke not specified 10.2% coronary disease not spec. 8.4% transient ischemic attack 5.1% ischemic stroke 4.2% unheralded coronary death 4.0% unstable angina 1.6% arrhythmia or sudden cardiac death 1.4% intracerebral hemorrhage 1.0% aortic aneurysm 0.2% subarachnoid hemorrhage

14 Swiss recommendations 2016 Symptomatic cardiovasular disease? Swedish National Diabetes Register individuals with type 2 diabetes Age: 65 years Coronary Heart Disease: 17.3% Acute Myocardial Infarction: 9.1 Stroke: 6.6% Amputation: 0.4% Atrial fibrillation 7.6% Heart failure: 6.6% 24.3% Rawshani A. et al, NEJM 2017, 376:

15 4 th clinical question: Asymptomatic Heart Failure? 581 Patients >60 years with T2D and no none heart failure in primary care HFpEF: 22.9% HFrEF: 4.8% 27.6% Asymptomatic, diagnosed with echocardiography 25% of Patients >60 years have asymptomatic heart failure 1. SSED/SGED guidelines update. HFrEF: 4.8% Diabetologia Aug; 55(8): HFpEF: 22.9%

16 4 th clinical question: Symptomatic Heart Failure? Diagnosed clinically? 9591 individuals with type 2 diabetes Kaiser Permanente, Oregon, USA 64 years old 4.8 years diabetes duration 25% with coronary heart disease 52% with hypertension 19.7% on insulin Prevalence 11.8% vs. 4.5% (without diabetes) Incidence per year 7.7% vs. 3.4% (without diabetes) Age = major risk factor Prevalence yrs: 3.3% yrs: 6.8% yrs: 13.5% Incidence yrs: 1.0% yrs: 2.6% yrs: 3.4% 2x 2x Nichols GA et al. Diabetes Care 2001; 24:

17 1 st step: individual HbA1c-Target 2 nd step: best individual therapy for patients: Setting which priorities? 3 rd step: Think in drug classes: choose the substance with the best evidence

18 Classes+Substances Product Name Combination with Metformin Biguanides Metformin Glucophage or Generics SGLT-2-Inhibitors Canagliflozin Invokana (2x mehr Amputationen) Vokanamet Dapagliflozin Forxiga Xigduo XR* Empagliflozin Jardiance Jardiance Met DPP-4-Inhibitors Alogliptin Vipidia Vipdomet Linagliptin Trajenta Jentadueto Saxagliptin Onglyza Kombiglyze XR* Sitagliptin Januvia, Xelevia Janumet, -XR*, Velmetia Vildagliptin Galvus Galvumet Sulfonylurea Gliclazide Diamicron or Generika Glibenclamide Daonil /Semi-Daonil or Genercs Glucovance /- mite Glimepiride Amaryl or Generics Drugs in red have better evidence for reduction of mortality, as well as micro-and macro-vascular complications and should be prefered

19 Class/Substance Product Name Combination GLP-1 Rezeptor Agonists (Glucagon-Like Peptide 1) Exenatide Byetta (2x daily) Exenatide Slow Release Bydureon Pen (1x weekly) Liraglutide Victoza (1x daily) + Degludec: Xultophy Semaglutide Dulaglutide Trulicity (1x weekly) analogs, long-acting Degludec* Tresiba + Liraglutid: Xultophy Detemir Levemir Glargine Lantus - Glargine 300 Toujeo SoloStar ( tested, but not longer duration) - Glargine-Biosimilar Abasaglar Human insulin, intermediate duration of action NPH Huminsulin, Insulatard analogs, short-acting Lispro Humalog Aspart NovoRapid Glulisin Apidra Premixed insulins with short- and long-acting insulin analogs or NPH- Lispro Humalog Humalog Mix (NPH-) Aspart NovoRapid NovoMix (NPH ) Degludec/Aspart NovoRapid Ryzodeg (Degludec) Drugs in red have better evidence for reduction of mortality, and micro-and macro-vascular complications and should be prefered

20 Swiss recommendations 2016 Swiss Society of Endocrinology and Diabetology 1. Deficiency? ~25% of all patients Basal Premixed- Basal + GLP-1 RA (Xultophy ) or Basal Bolus 2. egfr < 30 ml/min? 3. Cardiovascular Disease? 4. Heart Failure? 2.4% of all patients yes no ~ 10% of all patients (~25% asymptomatic) DPP-4 Inhibitors ~20-25% of all patients (~50% asymptomatic) SGLT2 I. GLP-1 RA SGLT2 I. or GLP-1 RA SGLT2 I. or + DPP-4 I. Basal Metformin + DPP-4 I. ~25% e-gfr < %: e-gfr %: e-gfr DPP-4 I. or Gliclazide or Basal + Gliclazide or Basal + Gliclazide or Basal Basal