XIX Congresso Nazionale AMD Insulina basale e GLP-1 RA. Dipartimento di Medicina Interna Università di Perugia

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1 XIX Congresso Nazionale AMD Insulina basale e GLP-1 RA Gabriele Perriello Dipartimento di Medicina Interna Università di Perugia Insulina: i benefici di un trattamento tempestivo nel DMT2 Roma, 31 maggio 2013

2 Approccio tempestivo/ intensivo nel DMT2 Approccio STEPWISE Ogni step può potenzialmente prolungare l esposizione all effetto glucotossico, che contribuisce al deterioramento della betacellula e delle complicanze micro e macrovascolari 2 Approccio tempestivo/ intensivo orientato al paziente Nel diabete tipo 2 la terapia insulinica e inizialmente aggiunta alla terapia orale (aggiungendo glargine, o detemir, o umana NPH, o lispro NPH la sera, oppure piccoli boli di analogo rapido ai pasti) per poi, se necessario, essere adattata o intensificata secondo lo schema basal-bolus o, in rari casi selezionati, con premiscelate. 1. Standard Italiani per la cura del diabete mellito Roman G et al. Horm Metab Res 2009;41:

3 PKD of different basal insulins in T1DM median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001) Porcellati elt al. Diabetes Care 30: , 2007

4 Modello di studio Treat-To-Target Insulin-naïve T2DM patients (n=756): aged 55 years; BMI 32 kg/m 2 ; diabetes duration 8 9 years on 1 or 2 OHAs; HbA1c % Weekly forced-titration schedule to FPG <100 mg/dl (5.5 mmol/l) OHAs NPH insulin + continued OHAs Insulin glargine + continued OHAs Week 4 (recruitment) Week 0 (baseline) Week 24 (endpoint) Screening Titration and treatment phase Insulin starting dose: 10 units/day Hypoglycaemia: PG <4 mmol/l (<72 mg/dl) BMI=body mass index. Riddle M, et al. Diabetes Care 2003;26:

5 Studio LANMET: algoritmo di titolazione Patients self-adjusted dose FPG values transferred by modem to diabetes monitoring centre Insulin dose titrated to FPG mmol/l ( mg/ dl) Measure FPG daily for 3 days If mean of FPG measurements >5.6 mmol/l (>100 mg/dl) ADD 2 UNITS OF BASAL INSULIN No increase in dose if FPG <4.0 mmol/l (<72 mg/dl) FPG=fasting plasma glucose. Yki-Jarvinen H et al. Diabetologia. 2006;49:442-51

6 Median Glargine Dose & IQR (U/kg) Median (IQR) 28 (19-39) U/d in 70 Kg Person

7 Adherence to Insulin Glargine in 6264 Allocated to Insulin Permanently Stopped During the Trial (%) N stopped drug 19 Reason for Stopping Refusal 90 Hypoglycemia 4 Weight Gain 0.3 Hyperglycemia 0.3 Other 5

8 Hypoglycemia & Weight (6-7 years) Glargine (N=6264) Standard (N=6273) % /100py % /100py Any Non- severe 1 or more episodes <0.001 Severe 1 or more episodes <0.001 P Weight Change Since Randomized Glargine Standard P 1.6 kg (3.5 lbs) -0.5 kg (1 lb) <0.001

9 Median FPG in all patients

10 Median FPG by subgroups Median FPG mmol/l No diabetes Standard Glargine Std Glar Median FPG mmol/l Std Glar Diabetes Years of treatment Standard Glargine End

11 Median A1C Levels in all patients IQR IQR

12 Percent <7.0% A1C by subgroups Percentage A1C <7.0% No diabetes Glargine Standard Percentage A1C <7.0% Diabetes Glargine Standard Years of treatment

13 Percent with A1C <6.5% at 1 and 5 years Baseline 1 year 5 years No diabetes Glargine Standard Diabetes Glargine Standard

14 Main independent predictors* of maintaining mean A1C <6.5% up to 5 y Odds ratio (95% CI) p DM vs no DM 0.31 ( ) <0.001 Baseline A1C (per 1%) 0.19 ( ) <0.001 Alcohol use (>2x/wk) 1.61 ( ) <0.001 Glargine vs Standard 2.98 ( ) <0.001 *Fully adjusted logistic regression model

15 Conclusions Glargine (0,4 U/kg) is well tolerated (>80% of treated patients) over 6-7 years Low risk of hypoglycemia & minimal weight gain Early target-directed intervention can maintain nearnormal A1C levels for at least 5 years The glargine-based regimen is more likely to keep A1C <6.5% (three times vs standard therapy) Clear answers to patient s questions Basal insulin glargine has a neutral effect on CV events Basal insulin glargine reduces progression of diabetes Basal insulin glargine has a neutral effect on cancers

16 XIX Congresso Nazionale AMD Insulina basale e GLP-1 RA Gabriele Perriello Dipartimento di Medicina Interna Università di Perugia Grazie per la vostra attenzione Roma, 31 maggio 2013