Nuove prospettive nella terapia della PCOS: Ruolo dei GLP-1 RA. Edoardo Mannucci

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1 Nuove prospettive nella terapia della PCOS: Ruolo dei GLP- RA 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 Actual and potential indications of GLP-RAs Type 2 diabetes Obesity Type diabetes associated with overweight/obesity Cardiovascular protection in high-risk patients with diabetes Prevention of CKD in patients with diabetes NAFLD PCOS 3

4 Effect of exenatide on non-diabetic women with PCOS Results of a RCT Exenatide vs metformin 2 g/d or combination exe+met N=60 Patients: PCOS, BMI>27 Duration of trial: 24 wk Principal endpoint: cyclicity Elkind-Hirsch et al. J Clin Endocrinol Metab 4 937:2670-8, 2008

5 Effect of liraglutide on body weight in women with PCOS Results of an open-label RCT RCT, liraglutide.2 mg vs metformin vs PDE5 inhibitor roflumilast, 2 wk N=45 women with PCOS and BMI>30 (N=4 completers) Jensterle M et al. J 5Ovar Res 8:32, 205

6 Effect of liraglutide on body weight in women with PCOS Analysis of patients from 2 RCTs N=57 women with PCOS and BMI>30 enrolled in trials (N=2) with liraglutide.2mg Jensterle M et al. Eur J Clin Pharmacol 6 7:87-24, 205

7 Effect of liraglutide on body composition in women with PCOS Results of the LIPT study DB RCT, liraglutide.8 mg vs placebo 2:, 26 wk N=57 (PP) women with PCOS and BMI>25; assessment with DEXA and MRI Frøssing et al. Diabet 7 Obes Metab 207

8 Liraglutide and thrombogenic potential in women with PCOS Results of a randomized clinical trial Treatments: Liraglutide.8mg vs placebo, 2:, for 26 wk Patients: 72 women with PCOS Principal outcome: weight loss Nylander M et al. Endocr Connect 8 6:89-99, 207

9 Liraglutide in women with PCOS Meta-analysis of randomized trials Testosterone SHBG Niafar M et al. Arch Gynecol Obstet 9 293:509-5, 206

10 Exenatide BID vs metformin in women with PCOS Results of a randomized clinical trial Treatments: Exenatide 0 mcg BID vs metformin g BID for 2 wk, all metformin for further 2 wk Patients: 76 women with PCOS, aged 8-40, BMI>24 Principal outcome: weight loss No between-group difference in androgens and LH/FSH 0 Liu X et al. Clin Endocrinol 207

11 Liraglutide and menstrual cyclicity in women with PCOS Results of a randomized clinical trial with liraglutide.8 vs placebo for 26 wk Patients: 72 women with PCOS; Principal outcome: weight loss Nylander M et al. Reprod Biomed Online 35:2-7, 207

12 Effect of exenatide on non-diabetic women with PCOS Results of a RCT Exenatide vs metformin 2 g/d or combination exe+met N=60 Patients: PCOS, BMI>27 Duration of trial: 24 wk Principal endpoint: cyclicity Elkind-Hirsch et al. J Clin Endocrinol Metab 937:2670-8,

13 Effect of bariatric surgery in PCOS Meta-analysis of observational studies Prevalence of hyrsutism, post- vs pre-surgery Skubleny D et al. Obes Surg 26:69 76, 206 3

14 Effect of GLP on insulin sensitivity Clamp studies in healthy rats, acute GLP infusion 4 Chai W et al. Diabetes 63: , 204

15 Effect of GLPRA on adiponectin expression In vitro studies on human adipocyte precursors from subcutaneous fat Cantini G et al. Mol Cell Endocrinol 402:43-50, 205 5

16 Effect of metformin in PCOS Diamanti-Kandarakis E et al. Eur J Endocrinol 62: 93-23, 200 6

17 Effect of addition of metformin to liraglutide in PCOS Results of a RCT Liraglutide.2mg monoth. vs combo with metformin Patients: PCOS, BMI>30 N=44 Duration of trial: 24 wk Principal endpoint: body weight Elkind-Hirsch et al. Exp Ther Med :94-200, 206 7

18 Effect of metformin addition to liraglutide in PCOS Results of a 2-wk open-label RCT N=30 women with PCOS and BMI>30 Jensterle M et al. BMC Endocr Disord 7:5, 207 8