Effectiveness of GLP1-RAs in type 2 diabetes: a gender analysis

Alessandro Cuttone, Annalisa Giandalia, Andrea Muscarà, Letterio Giorgianni, Carmela Morace, Giovanni Squadrito, Domenico Cucinotta, Giuseppina Russo

Abstract


In type 2 diabetes (T2D), several differences have been described between men and women, concerning risk factors, clinical manifestations and chronic complications. The impact of gender on the efficacy and safety of hypoglycaemic drugs is still to be clarified. Some data suggest that GLP1-RAs may have greater efficacy on body weight in women, but comparable efficacy on glycaemic control and cardiovascular risk (CVD) in both sexes. The aim of our study was to evaluate in real-life clinical practice the possible influence of gender on the effectiveness and safety of GLP1-RAs long-acting therapy in T2D outpatients. In this single-centre observational study, we evaluated laboratory parameters, chronic complications, hypoglycaemic episodes, and any adverse events of subjects with T2D who started treatment with GLP1-RAs long-acting between  1 June 2018 and 31 May 2019, in add on to metformin or other hypoglycaemic drugs, and who practiced this therapy for at least two years. In the present analysis, 391 subjects with T2D were included (men 59.3%, women 40.7%), with a mean age of 64.1 years and mean duration of diabetes of 18.4 years. At baseline, patients were on average obese (BMI 32.8 kg/m2) with an inadequate glycaemic control (HbA1c 7.8%). Women had higher BMI values than men; glycaemic control was similar in both genders. After two years of follow-up, therapy with GLP1-RAs long-acting determined a significant reduction of BMI and blood pressure values, HbA1c, fasting glucose and GPT levels and an improvement in lipid profile. The reduction observed in BMI values was significantly greater in T2D women than in men. At stepwise regression analysis, female gender was among the independent predictors of the effectiveness of GLP1-RAs in terms of BMI reduction, together with fasting blood glucose, but not in terms of reduction of HbA1c levels, which was significantly associated with baseline blood glucose levels and metformin use, irrespective of gender. Overall, the treatment with GLP1-RAs was well tolerated, and only mild gastro-intestinal adverse events were observed (n=22; 5.6%, 14 men and 12 women P>0.05), in both genders. In conclusion, in real-life clinical practice, the therapy with GLP1-RAs long-acting is safe and effective in both men and women, and it seems to be associated with a more beneficial effect on body weight in women than in men.

Keywords


type 2 diabetes, GLP1-RAs, gender differences

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References


1. Bonora, E. (2022). La pandemia diabete in Italia. L'Endocrinologo. 23, 337–344. https://doi.org/10.1007/s40619-022-01130-4.

2. American Diabetes Association. (2021). Standards of Medical Care in Diabetes-2022. Diabetes Care. 45, S1-S2. doi: https://doi.org/10.2337/dc22-Sint.

3. Yeo, J.L., Brady, E.M., McCann, G.P., Gulsin, G.S. (2021). Sex and ethnic differences in the cardiovascular complications of type 2 diabetes. Ther Adv Endocrinol Metab. 4, 12:20420188211034297. doi: 10.1177/20420188211034297.

4. Schütt, M., Zimmermann, A., Hood, R., Hummel, M., Seufert, J., Siegel, E., Tytko, A., Holl, R. (2015). Gender-specific Effects of Treatment with Lifestyle, Metformin or Sulfonylurea on Glycemic Control and Body Weight: A German Multicenter Analysis on 9 108 Patients. Experimental and Clinical Endocrinology & Diabetes. 10, 622-6. doi: 10.1055/s-0035-1559608.

5. Kautzky-Willer, A., Harreiter, J. (2017). Sex and gender differences in therapy of type 2 diabetes. Diabetes e Clin Pract. 131, 230-241. doi: 10.1016/j.diabres.2017.07.012. Epub 2017 Jul 13.

6. Russo, G.T., Giandalia, A., Romeo, E.L., Nunziata, M., Muscianisi, M., Ruffo, M.C., Catalano, A., Cucinotta, D. (2016). Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences. Int J Endocrinol. 1615735. doi: 10.1155/2016/1615735. Epub 2016 Dec 4.

7. Rentzeperi, E., Pegiou, S., Koufakis, T., Grammatiki, M., Kotsa, K. (2022). Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care. J. Pers. Med. 12, 454. doi: 10.3390/jpm12030454.

8. Pencek, R., Blickensderfer, A., Li, Y., Brunnell, S.C., Chen, S. (2012). Exenatide once weekly for the treatment of type 2 diabetes:effectiveness and tolerability in patient subpopulations. Int J Clin Pract. 66, 1021-1032. doi: 10.1111/j.1742-1241.2012.03006.x. Epub 2012 Aug 24.

9. Mirabelli, M., Chiefari, E., Caroleo, P., Arcidiacono, B., Corigliano, D.M., Giuliano, S., Brunetti, F.S., Tanyolaç, S., Foti, D.P., Puccio, L., Brunetti, A. (2019). Long-Term Effectiveness of Liraglutide for Weight Management and Glycemic Control in Type 2 Diabetes. Int J Environ Res Public Health. 27, 17(1):207. doi: 10.3390/ijerph17010207.

10. Overgaard, R.V., Petri, K.C.C., Jacobsen, L.V., Jensen, C.B. (2016). Liraglutide 3.0 mg for Weight 10. anagement: A Population Pharmacokinetic Analysis. Clin. Pharmacokinet. 55(11), 1413-1422. doi: 10.1007/s40262-016-0410-7.

11. Raparelli, V., Elharram, M., Moura, C.S., Abrahamowicz, M., Bernatsky, S., Behlouli, H., Pilote, L. (2020). Sex Differences in Cardiovascular Effectiveness of Newer Glucose-Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus. Journal of the American Heart Association. 9, e012940. doi.org/10.1161/JAHA.119.012940

12. Anichini, R., Cosimi, S., Di Carlo, A., Orsini, P., De Bellis, A., Seghieri, G., Franconi, F., Baccetti, F. (2013). Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience. Diabetes Metab Syndr Obes. 6, 123-129. doi: 10.2147/DMSO.S42729.

13. Fadini, G.P., Simioni, N., Frison, V., Dal Pos, M., Bettio, M., Rocchini, P., Avogaro, A. (2013). Independent glucose and weight-reducing effects of Liraglutide in a real-world population of type 2 diabetic outpatients. Acta Diabetol. 50(6), 943-9. doi: 10.1007/s00592-013-0489-3. Epub 2013 Jun 11

14. Russo, G.T., Labate, A.M., Giandalia, A., Romeo, E.L., Villari, P., Alibrandi, A., Perdichizzi, G., Cucinotta, D. (2014). Twelve -month treatment with Liraglutide ameliorates Visceral Adiposity Index and common cardiovascular risk factors in type 2 diabetes outpatients. Endocrinol Invest. 38(1), 81-9. doi: 10.1007/s40618-014-0163-9. Epub 2014 Aug 31.




DOI: https://doi.org/10.13129/1828-6550/APMB.111.2.2023.OS1

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