DIABETEKSEN KÄYPÄ HOITO - SUOSITUKSEN PÄIVITYS Merja Laine

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1 DIABETEKSEN KÄYPÄ HOITO - SUOSITUKSEN PÄIVITYS Merja Laine

2 Tyypin 2 diabetes ja komplikaahot Diabeettinen Diabetic retinopatia retinopathy Leading cause Suurin of blindness sokeuteen johtava in working-age syy työikäisillä adults 1 aikuisilla 1 Diabetic nephropathy Diabeettinen nefropatia Leading cause of end-stage Suurin syy renal loppuvaiheen disease 2 munuaissairauteen 2 Aivohalvaus Stroke 2- to 4-fold increase in Aivohalvaus cardiovascular ja mortality SVT -kuolleisuus and stroke 3 lisääntyvät 2-4 -kertaisesti 3 Sydän ja Cardiovascular verisuonitauti disease 8/10 diabeetikosta kuolee SVT - tapahtumien seurauksena 4 Diabetic neuropathy Diabeettinen Leading neuropatia cause of non-traumatic lower Suurin syy extremity amputations ei-traumaattisiin 5 raaja-amputaatioihin 5 1. Fong et al. Diabetes Care 2003; 2. Molitch et al. Diabetes Care 2003; 3. Kannel et al. Am Heart J 1990; 4. Hogan et al Diabetes care 2003; 5. Mayfield et al. diabetes Care 2003

3 Diabetes Käypä Hoito suositus 2013

4 Diabetes Käypä Hoito suositus glukoosi - lipidit - verenpaine - ASAn mielekäs käymö - painon hallinta - ruokavalio - liikunta - tupakoino - alkoholin käymö

5 Tyypin 2 diabeteksen patofysiologia

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7 PATIENT / DISEASE FEATURES Risks potentially associated with hypoglycemia and other drug adverse effects more stringent low Approach to the management of hyperglycemia HbA1c& 7%&& less stringent high Disease duration newly diagnosed long-standing Life expectancy long short Usually not modifiable Important comorbidities absent few / mild severe Established vascular complications absent few / mild severe Patient attitude and expected treatment efforts highly motivated, adherent, excellent self-care capacities less motivated, non-adherent, poor self-care capacities Potentially modifiable Resources and support system Readily available limited Diabetes Care 2015;38: ; Diabetologia 2015;58:

8 Diabetes käypä hoito 2013

9 ADA/EASD 2015

10 Hoidon seuranta Diabetes KH 2013

11 CV death is increased in pahents with diabetes and mulhple risk factors Age- adjusted CVD death risk/10,000 person- years Number of risk factors Diabetes No diabetes Risk factors were serum cholesterol 200 mg/dl, current smoker, SBP 120 mmhg Stamler et al. Diabetes Care 1993;16:434.

12 34.7 % tyypin 2 diabeehkoista on merkiwävä munuaisvaurio (egfr < 60 ml/min ja/tai albuminuria) Metsärinne K, Bröijersen A, Kantola I, Niskanen L, Rissanen A, Appelroth T, Pöntynen N, Poussa T, Koivisto V, Virkamäki A. Primary Care Diabetes 2014.

13 Meaormiini ja munuaisten vajaatoiminta kreacl ml/min: meaormiinia voi jatkaa, munuaistoiminnan kontrolli 3-6kk välein kreacl ml/min: erityinen varovaisuus, 50% pienennemy annos tai puolet maksimista, ei uuma aloitusta, tarkka monitoroino kreacl <30 ml/min: meaormiinin lopetus tauotus akuuon sairauden yhteydessä, erityistä tarkkuuma monisairailla ja polyfarmasiassa Diabetes Care 2011;34:

14 Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement.

15 Diabetes käypä hoito 2013

16 sic! 4/2013, Jorma Lahtela

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20 HOITOSUUNNITELMA HoitotavoiMeiden pohominen poolaan kanssa yhdessä Kontrollit - mitä - milloin - kenellä

21 Diabetes käypä hoito 2013

22 Diabetes is associated with significant loss of life years Men Women 7 6 Non-vascular deaths Vascular deaths 7 6 Years of life lost Age (year) Age (year) On average, a 50-year old with diabetes but no history of vascular disease is ~6 years younger at time of death than a counterpart without diabetes Seshasai et al. N Engl J Med 2011;364:

23 Glucose- lowering studies confirmed benefit on microvascular complicahons but mixed results on macrovascular outcomes Study 1 Baseline HbA 1c Control vs intensive Mean duration of diabetes at baseline (years) Microvascular CVD Mortality UKPDS 9% 7.9% vs 7% Newly diagnosed ACCORD % 7.5% vs 6.4% 10.0 * ADVANCE 7.5 % 7.3% vs 6.5% 8.0 ** VADT 9.4 % 8.4% vs 6.9% 11.5? Long- term follow- up 1,4,5 *No change in primary microvascular composite but significant decreases in micro/ macroalbuminuria 2,3 **No change in major clinical microvascular events but significant reducoon in ESRD (p = 0.007) 5 1. Table adapted from Bergenstal et al. Am J Med 2010;123:374.e9 e Genuth et al. Clin Endocrinol Metab 2012;97: Ismail- Beigi et al. Lancet 2010;376: Hayward et al. N Engl J Med 2015;372: (VADT). 5. Zoungas et al. N Engl J Med 2014;371:

24 Urinary glucose excretion via SGLT2 inhibition1 Filtered glucose load > 180 g/day SGLT2 SGLT2 inhibitor SGLT1 1. Bakris et al. Kidney Int 2009;75; SGLT2 inhibitors reduce glucose reabsorption in the proximal tubule, leading to urinary glucose excretion* and osmotic diuresis

25 EMPA-REG OUTCOME : Study design Aim Compound-specific To determine CV safety of empagliflozin vs placebo + usual care for glycaemic control and CV risk in patients with T2D and high CV risk 12 weeks of stable background glucose-lowering therapy Background therapy adjustment allowed after Week 12 2 weeks Placebo run-in Screening (n = 11,507) Empagliflozin 10 mg QD + usual care Follow-up Placebo + usual care Empagliflozin 25 mg QD + usual care Visit 1-3 Visit 2-2 Visit 3 Visits 4 7 every 4 weeks Week Zinman et al. Cardiovasc Diabetol 2014;13:102. End of Visits 8 10 Visits every study every 12 weeks 14 weeks visit days

26 CV death Empagliflozin 10 mg HR 0.65 (95% CI 0.50, 0.85) p= Empagliflozin 25 mg HR 0.59 (95% CI 0.45, 0.77) p= Cumulative incidence function. HR, hazard ratio 26

27 Hospitalisation for heart failure Empagliflozin 10 mg HR 0.62 (95% CI 0.45, 0.86) p= Empagliflozin 25 mg HR 0.68 (95% CI 0.50, 0.93) p= Cumulative incidence function. HR, hazard ratio 27

28 All-cause mortality Empagliflozin 10 mg HR 0.70 (95% CI 0.56, 0.87) p= Empagliflozin 25 mg HR 0.67 (95% CI 0.54, 0.83) p= HR 0.68 (95% CI 0.57, 0.82) p< Kaplan-Meier estimate. HR, hazard ratio 28

29 Empagliflozin modulates several factors related to CV risk!bp!arterial stiffness Other!Albuminuria!Sympathetic nervous system activity!glucose!insulin!uric acid!weight!visceral adiposity LDL-C HDL-C!Triglycerides!Oxidative stress Adapted from Inzucchi SE,Zinman, B, Wanner, C et al. Diab Vasc Dis Res 2015;12:90-100