Du gusts is megl che one. Edoardo Mannucci

Transcription

1 Du gusts is megl che one Edoardo Mannucci

2 Conflitti di interessi Negli ultimi due anni, E. Mannucci ha ricevuto compensi per relazioni e/o consulenze da: Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, and Takeda. La struttura diretta da E. Mannucci ha ricevuto donazioni, finanziamenti per ricerca o compensi per trial clinici da: AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, and Novo Nordisk. 2

3 Du gust is megl che one

4 Available fixed combinations in Italy Sulfonylureas plus metformin Pioglitazone plus metformin DPP4 inhibitors plus metformin DPP4 inhibitors plus pioglitazone SGLT2 inhibitors plus metformin GLP receptor agonists plus basal insulin SGLT2 inhibitors plus DPP4 inhibitors 4

5 Oral treatment in type 2 diabetes in Italy, ARNO database Gaddi AV et al. Publ Health 5 28:70-76, 204

6 Terapia del diabete: il presente 6

7 Initial combo met+dpp4i versus metformin monotherapy Meta-analysis of RCTs We H et al. Diabetes Obes Metab 7 6:30-37, 204

8 Advantages of fixed combinations Greater convenience Higher adherence Lower cost 8

9 Available fixed combinations in Italy Sulfonylureas plus metformin Pioglitazone plus metformin DPP4 inhibitors plus metformin DPP4 inhibitors plus pioglitazone SGLT2 inhibitors plus metformin GLP receptor agonists plus basal insulin SGLT2 inhibitors plus DPP4 inhibitors 9

10 Conditions for the use of fixed combinations Both drugs have a favorable risk/benefit ratio The therapeutic effects are at least partly additive There is no safety issue arising from the combination of the two drugs There is no need for dose titration of any of the two components 0

11 SU + metformin and cardiovascular events Results of the UKPDS Endpoint HR [95%CI] Principal endpoint: Long-term diabetic complications All-cause mortality.60 [ ] Cardiovascular mortality.96 [ ] Myocardial infarction.09 [ ] Stroke.2 [ ] 537 T2DM patients inadequately controlled on sulfonylurea alone Treatment: metformin + SU (vs SU alone), follow-up 6 y UKPDS Group. Lancet 352:854-65, 998

12 Combinations of sulfonylureas and metformin: mortality Results of a retrospective observational cohort study Principal endpoint: All-cause mortality 927 T2DM patients treated with fixed combination of sulfonylureas and low-dose metformin. Mean follow-up 55. months Mannucci E et al. Diabetes Metab Res Rev 20:44-7,

13 Conditions for the use of fixed combinations Both drugs have a favorable risk/benefit ratio The therapeutic effects are at least partly additive There is no safety issue arising from the combination of the two drugs There is no need for dose titration of any of the two components 3

14 Combinations of basal insulin and once-daily GLPRAs , Liraglutide Degludec Lixisenatide Glargine 4

15 ideglira in comparison with degludec and liraglutide: HbAc Results of a double-blind, placebo-controlled randomized trial (DUAL-I) Principal endpoint: HbAc at 24 wk,663 T2DM patients inadequately controlled on metformin Gough C et al. Lancet Diabetes Endcorinol 2:885-93, 204 5

16 ideglira in comparison with degludec and liraglutide: body weight Results of a double-blind, placebo-controlled randomized trial (DUAL-I) Principal endpoint: HbAc at 24 wk,663 T2DM patients inadequately controlled on metformin Gough C et al. Lancet Diabetes Endcorinol 2:885-93, 204 6

17 ideglira in comparison with degludec and liraglutide: hypoglycemia Results of a double-blind, placebo-controlled randomized trial (DUAL-I) Principal endpoint: HbAc at 24 wk,663 T2DM patients inadequately controlled on metformin Gough C et al. Lancet Diabetes Endcorinol 2:885-93, 204 7

18 Liraglutide: effect on major cardiovascular events Results of the LEADER trial Principal endpoint: 3-point MACE (nonfatal MI, nonfatal stroke, and cardiovascular death) 9,340 T2DM patients with prior cardiovascular disease and/or high CV risk, Liraglutide vs placebo :. Follow-up: 4 y Marso SP et al. N Engl J Med 375: 3-22, 206 8

19 Liraglutide: effect on all-cause mortality Results of the LEADER trial Secondary endpoint: All-cause mortality 9,340 T2DM patients with prior cardiovascular disease and/or high CV risk, Liraglutide vs placebo :. Follow-up: 4 y Marso SP et al. N Engl J Med 375: 3-22, 206 9

20 Available fixed combinations in Italy Sulfonylureas plus metformin Pioglitazone plus metformin DPP4 inhibitors plus metformin DPP4 inhibitors plus pioglitazone SGLT2 inhibitors plus metformin GLP receptor agonists plus basal insulin SGLT2 inhibitors plus DPP4 inhibitors 2 0