Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy

Author(s): Castellano Elena*, Giorgio Borretta, Roberto Attanasio, Boriano Alberto, Daniela Agrimi, Nicola Argese, Cassandra Crescenti, Olga Disoteo, Alessandra Fusco, Enrico Gabellieri, Rinaldo Guglielmi, Giuseppe Lisco, Feliciano Lo Pomo, Maurizio Nizzoli, Annalisa Panico, Barbara Pirali, Antonio Stefano Salcuni, Federica Turchi and Franco Grimaldi

Volume 23, Issue 6, 2023

Published on: 04 January, 2023

Page: [818 - 825] Pages: 8

DOI: 10.2174/1871530323666221115091621

open access plus

Abstract

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients.

Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi).

Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration.

Conclusion: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

Keywords: Type 2 diabetes mellitus, metformin, dosage, HbA1c level, first-line treatment, anti-diabetic drug.

Graphical Abstract
[1]
Bellary, S.; Kyrou, I.; Brown, J.E.; Bailey, C.J. Type 2 diabetes mellitus in older adults: Clinical considerations and management. Nat. Rev. Endocrinol., 2021, 17(9), 534-548.
[http://dx.doi.org/10.1038/s41574-021-00512-2] [PMID: 34172940]
[2]
Khan, M.A.B.; Hashim, M.J.; King, J.K.; Govender, R.D.; Mustafa, H.; Al Kaabi, J. Epidemiology of type 2 diabetes – global burden of disease and forecasted trends. J. Epidemiol. Glob. Health, 2019, 10(1), 107-111.
[http://dx.doi.org/10.2991/jegh.k.191028.001] [PMID: 32175717]
[3]
Sesti, G.; Antonelli Incalzi, R.; Bonora, E.; Consoli, A.; Giaccari, A.; Maggi, S.; Paolisso, G.; Purrello, F.; Vendemiale, G.; Ferrara, N. Management of diabetes in older adults. Nutr. Metab. Cardiovasc. Dis., 2018, 28(3), 206-218.
[http://dx.doi.org/10.1016/j.numecd.2017.11.007] [PMID: 29337017]
[4]
Schernthaner, G.; Schernthaner, G.H. The right place for metformin today. Diabetes Res. Clin. Pract., 2020, 159, 107946.
[http://dx.doi.org/10.1016/j.diabres.2019.107946] [PMID: 31778746]
[5]
9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care, 2022, 45(S1), S125-S143.
[http://dx.doi.org/10.2337/dc22-S009]
[6]
Buse, J.B.; Wexler, D.J.; Tsapas, A.; Rossing, P.; Mingrone, G.; Mathieu, C.; D’Alessio, D.A.; Davies, M.J. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 2020, 43(2), 487-493.
[http://dx.doi.org/10.2337/dci19-0066] [PMID: 31857443]
[7]
The American Diabetes Association (ADA). Older Adults: Standards of Medical Care in Diabetes—2020. Diabetes Care, 2020, 43(Suppl. 1), S152-S162.
[http://dx.doi.org/10.2337/dc20-S012] [PMID: 31862755]
[8]
DeFronzo, R.; Fleming, G.A.; Chen, K.; Bicsak, T.A. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism, 2016, 65(2), 20-29.
[http://dx.doi.org/10.1016/j.metabol.2015.10.014] [PMID: 26773926]
[9]
Bonora, E.; Cataudella, S.; Marchesini, G.; Miccoli, R.; Vaccaro, O.; Fadini, G.P.; Martini, N.; Rossi, E. Initial treatment of diabetes in Italy. A nationwide population-based study from of the ARNO Diabetes Observatory. Nutr. Metab. Cardiovasc. Dis., 2021, 31(9), 2661-2668.
[http://dx.doi.org/10.1016/j.numecd.2021.06.006] [PMID: 34218990]
[10]
Mahabaleshwarkar, R.; DeSantis, A. Metformin dosage patterns in type 2 diabetes patients in a real-world setting in the United States. Diabetes Res. Clin. Pract., 2021, 172, 108531.
[http://dx.doi.org/10.1016/j.diabres.2020.108531] [PMID: 33157115]
[11]
Iglay, K.; Sawhney, B.; Fu, A.Z.; Fernandes, G.; Crutchlow, M.F.; Rajpathak, S.; Khunti, K. Dose distribution and up‐titration patterns of metformin monotherapy in patients with type 2 diabetes. Endocrinol. Diabetes Metab., 2020, 3(1), e00107.
[http://dx.doi.org/10.1002/edm2.107] [PMID: 31922032]
[12]
Kidney disease. Improving global outcomes (KDIGO) CKD work group. 2013 KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl., 2013, 3, 1-150.
[13]
Schaeffner, E.S.; Ebert, N.; Delanaye, P.; Frei, U.; Gaedeke, J.; Jakob, O.; Kuhlmann, M.K.; Schuchardt, M.; Tölle, M.; Ziebig, R.; van der Giet, M.; Martus, P. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann. Intern. Med., 2012, 157(7), 471-481.
[http://dx.doi.org/10.7326/0003-4819-157-7-201210020-00003] [PMID: 23027318]
[14]
Baker, C.; Retzik-Stahr, C.; Singh, V.; Plomondon, R.; Anderson, V.; Rasouli, N. Should metformin remain the first-line therapy for treatment of type 2 diabetes? Ther. Adv. Endocrinol. Metab., 2021, 12, 1-13.
[http://dx.doi.org/10.1177/2042018820980225] [PMID: 33489086]
[15]
Bonnet, F.; Scheen, A. Understanding and overcoming metformin gastrointestinal intolerance. Diabetes Obes. Metab., 2017, 19(4), 473-481.
[http://dx.doi.org/10.1111/dom.12854] [PMID: 27987248]
[16]
Nunes, B.P.; Flores, T.R.; Mielke, G.I.; Thumé, E.; Facchini, L.A. Multimorbidity and mortality in older adults: A systematic review and meta-analysis. Arch. Gerontol. Geriatr., 2016, 67, 130-138.
[http://dx.doi.org/10.1016/j.archger.2016.07.008] [PMID: 27500661]
[17]
Schlender, L.; Martinez, Y.V.; Adeniji, C.; Reeves, D.; Faller, B.; Sommerauer, C.; Al Qur’an, T.; Woodham, A.; Kunnamo, I.; Sönnichsen, A.; Renom-Guiteras, A. Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: A systematic review for the development of recommendations to reduce potentially inappropriate prescribing. BMC Geriatr., 2017, 17(S1), 227.
[http://dx.doi.org/10.1186/s12877-017-0574-5] [PMID: 29047344]
[18]
Disoteo, O.; Grimaldi, F.; Papini, E.; Attanasio, R.; Tonutti, L.; Pellegrini, M.A.; Guglielmi, R.; Borretta, G. State of the art review on diabetes care in Italy. Ann. Glob. Health, 2016, 81(6), 803-813.
[http://dx.doi.org/10.1016/j.aogh.2015.12.013] [PMID: 27108147]
[19]
Scarpello, J.H. Optimal dosing strategies for maximising the clinical response to metformin in type 2 diabetes. Br. J. Diabetes Vasc. Dis., 2001, 1(1), 28-36.
[http://dx.doi.org/10.1177/14746514010010010501]
[20]
Association of Diabetologists Doctors. AMD Annals. 2020. Available from: https://aemmedi.it/wp-content/uploads/2020/10/Annali-nuova-versione-2020_1-ok.pdf
[21]
Garber, A.J.; Duncan, T.G.; Goodman, A.M.; Mills, D.J.; Rohlf, J.L. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am. J. Med., 1997, 103(6), 491-497.
[http://dx.doi.org/10.1016/S0002-9343(97)00254-4] [PMID: 9428832]
[22]
Sivitz, W.I.; Phillips, L.S.; Wexler, D.J.; Fortmann, S.P.; Camp, A.W.; Tiktin, M.; Perez, M.; Craig, J.; Hollander, P.A.; Cherrington, A.; Aroda, V.R.; Tan, M.H.; Krakoff, J.; Rasouli, N.; Butera, N.M.; Younes, N.; Crandall, J.P.; Diane McKee, M.; Brown-Friday, J.; Xhori, E.; Ballentine-Cargill, K.; Duran, S.; Lukin, J.; Beringher, S.; Gonzalez de la torre, S.; Phillips, L.; Burgess, E.; Olson, D.; Rhee, M.; Wilson, P.; Stephanie Raines, T.; Costello, J.; Gullett, C.; Maher-Albertelli, M.; Morehead, F.; Mungara, R.; Person, S.; Savoye, L.; Sibymon, M.; Tanukonda, S.; Ann White, C.; Holloway, L.; Adams, C.; Ross, A.; Balasubramanyam, A.; Gonzalez, E.; Wright, C.; Hollander, P.; Roe, E.; Uy, A.; Burt, P.; Estrada, L.; Chionh, K.; Ismail-Beigi, F.; Falck-Ytter, C.; Sayyed Kassem, L.; Sood, A.; Tiktin, M.; Cramer, B.; Iacoboni, J.; Kononets, M.V.; Kulow, T.; Newman, C.; Stancil, K.A.; Sanders, C.; Tucker, L.; Werner, A.; Krol, A.; McPhee, G.; Patel, C.; Colosimo, L.; Goland, R.; Pring, J.; Kringas, P.; Tejada, J.; Hausheer, C.; Schneier, H.; Gumpel, K.; Kirpitch, A.; Green, J.B.; AbouAssi, H.; Chatterjee, R.; Feinglos, M.N.; English Jones, J.; Khan, S.A.; Kimpel, J.B.; Zimmer, R.P.; Furst, M.; Satterwhite, B.M.; Thacker, C.R.; Evans Kreider, K.; Mather, K.J.; Lteif, A.; Hamilton, T.; Patel, N.; Riera, G.; Jackson, M.; Pirics, V.; Howard, D.; Aguillar, D.; Hurt, S.; Bergenstal, R.; Carlson, A.; Martens, T.; Johnson, M.; Hill, R.; Hyatt, J.; Jensen, C.; Madden, M.; Martin, D.; Willis, H.; Konerza, W.; Passi, R.; Kleeberger, K.; Fortmann, S.; Herson, M.; Mularski, K.; Glauber, H.; Prihoda, J.; Ash, B.; Carlson, C.; Anne Ramey, P.; Schield, E.; Torgrimson-Ojerio, B.; Arnold, K.; Kauffman, B.; Panos, E.; Sahnow, S.; Bays, K.; Cook, J.; Gluth, J.; Sasaki, D.; Schell, K.; Criscola, J.; Friason, C.; Jones, S.; Nazarov, S.; Barzilay, J.; Rassouli, N.; Puttnam, R.; Curtis, M.; Stokes, K.; Hollis, B.; Sanders-Jones, C.; Nelson, R.; El-Haqq, Z.; Kolli, A.; Tran, T.; Wexler, D.; Mary, L.; Meigs, J.; Dushkin, A.; Rocchio, G.; Chambers, B.; Yepes, M.; Steiner, B.; Dulin, H.; Cayford, M.; DeManbey, A.; Gurry, L.; Hillard, M.; Martin, K.; Stevens, C.; Thangthaeng, N.; Kochis, R.; Raymond, E.; Ripley, V.; Park, J.; Aroda, V.; Ghazi, A.; Loveland, A.; Hurtado, M.; Kuhn, A.; Mofor, F.; Florez, H.J.; Valencia, W.M.; Marks, J.; Oropesa-Gonzalez, L.; Riccio Veliz, A.K.; Nieto-Martinez, R.; Gutt, M.; Ahmann, A.; Aby-Daniel, D.; Joarder, F.; Morimoto, V.; Sprague, C.; Yamashita, D.; Cady, N.; Kirchhoff, P.; Rivera-Eschright, N.; Adducci, J.; Gomez, B.M.; Goncharova, A.; Hox, S.H.; Petrovitch, H.; Matwichyna, M.; Jenkins, V.; Bermudez, N.O.; Ishii, R.R.; Hsia, D.S.; Cefalu, W.T.; Greenway, F.L.; Waguespack, C.; King, E.; Haynes, N.; Thomassie, A.; Bourgeois, B.; Hazlett, C.; Henry, R.; Mudaliar, S.; Boeder, S.; Pettus, J.; Diaz, E.; DeLue, C.; Castro, E.; Hernandez, S.; Krakoff, J.; Curtis, J.M.; Killean, T.; Joshevama, E.; Diaz, E.; Martin, D.; Karshner, T.; Albu, J.; Pi-Sunyer, F.X.; Frances, S.; Maggio, C.; Ellis, E.; Bastawrose, J.; Gong, X.; Ann Banerji, M.; August, P.; Lorber, D.; Brown, N.M.; Josephson, D.H.; Thomas, L.L.; Tsovian, M.; Cherian, A.; Jacobson, M.H.; Mishko, M.M.; Kirkman, M.S.; Bergamo, K.; Buse, J.B.; Dostou, J.; Young, L.; Goley, A.; Kerr, J.; Largay, J.F.; Guarda, S.; Cuffee, J.; Culmer, D.; Fraser, R.; Almeida, H.; Coffer, S.; Debnam, E.; Kiker, L.; Morton, S.; Josey, K.; Fuller, G.; Garvey, W.T.; Cherrington, A.; Golson, D.; Griffith, O.; Catherine Robertson, M.; Agne, A.; McCullars, S.; Cohen, R.M.; Craig, J.; Kersey, K.; Rogge, M.C.; Wilson, C.; Burton, K.; Lipp, S.; Vonder Meulen, M.B.; Rasouli, N.; Schroeder, E.; Steiner, S.; Baker, C.; Underkofler, C.; Douglass, S.; Sivitz, W.; Cline, E.; Knosp, L.; McConnell, J.; Lowe, T.; Herman, W.H.; Pop-Busui, R.; Tan, M.H.; Martin, C.; Waltje, A.; Goodhall, L.; Eggleston, R.; Kuo, S.; Bule, S.; Kessler, N.; LaSalle, E.; Seaquist, E.R.; Bantle, A.; Kumar, A.; Redmon, B.; Bantle, J.; Harindhanavudhi, T.; Coe, M.; Mech, M.; Taddese, A.; Lesne, L.; Smith, S.; Desouza, C.; Kuechenmeister, L.; Shivaswamy, V.; Laura Morales, A.; Rodriguez, M.G.; Seipel, K.; Alfred, A.; Eggert, J.; Lord, G.; Taylor, W.; Tillson, R.; Schade, D.S.; Adolphe, A.; Burge, M.; Duran-Valdez, E.; Martinez, J.; McGinnis, D.H.; Pucchetti, B.; Scripsick, E.; DeFronzo, R.A.; Cersosimo, E.; Abdul-Ghani, M.; Triplitt, C.; Verastiqui, H.; Irene Garza, R.; Wright, K.; Puckett, C.; Raskin, P.; Rhee, C.; Abraham, S.; Fan Jordan, L.; Sao, S.; Morton, L.; Smith, O.; Osornio Walker, L.; Schnurr-Breen, L.; Ayala, R.; Brian Kraymer, R.; Sturgess, D.; Utzschneider, K.M.; Kahn, S.E.; Alarcon-Casas Wright, L.; Boyko, E.J.; Tsai, E.C.; Trence, D.L.; Fattaleh, B.N.; Montgomery, B.K.; Atkinson, K.M.; Concepcion, T.; Kozedub, A.; Moak, C.; Rhothisen, S.; Elasy, T.A.; Martin, S.; Shackelford, L.; Goidel, R.; Hinkle, N.; Lipps Hogan, J.; Lovell, C.; Myers, J.; McGill, J.B.; Salam, M.; Kissel, S.; Schweiger, T.; Recklein, C.; Tamborlane, W.; Gatcomb, P.; Camp, A.; Gulanski, B.; Inzucchi, S.; Pham, K.; Alguard, M.; Lessard, K.; Perez, M.; Magenheimer, E.; Montoza, A.; Nathan, D.M.; Lachin, J.; Buse, J.B.; Kahn, S.E.; Krause-Steinrauf, H.; Larkin, M.; Tiktin, M.; Wexler, D.; Burch, H.B.; Linder, B.; Bremer, A.; Lachin, J.; Krause-Steinrauf, H.; Younes, N.; Backman, M.; Bebu, I.; Buys, C.J.; Fagan Murphy, A.; Gao, Y.; Gramzinski, M.; Hall, S.; Legowski, E.; Arey, A.; Bethepu, J.; Lund, C.; Mangat Dhaliwal, P.; McGee, P.; Mesimer, E.; Ngo, L.; Steffes, M.; Seegmiller, J.; Saenger, A.; Arends, V.; Gabrielson, D.; Conner, T.; Warren, S.; Day, J.; Scrymgeour, A.; Soliman, E.Z.; Zhang, Z-M.; Campbell, C.; Hu, J.; Keasler, L.; Hensley, S.; Li, Y.; Herman, W.; Martin, C.; Waltje, A.; Kuo, S.; Mihalcea, R.; Perez-Rosas, V.; Prosser, L.; Resnicow, K.; Ye, W.; Shao, H.; Zhang, P.; Luchsinger, J.; Sanchez, D.; Burch, H.B.; Bremer, A.; Linder, B.; Fradkin, J.; Groessl, E.; Chong, H.; Hillery, N.; Abdouch, I.; Brantley, P.; Broyles, F.E.; Canaris, G.; Copeland, P.; Craine, J.J.; Fein, W.L.; Lee, M.S.; Meiners, R.; Meiners, V.; O’Neal, H.; Park, J.E.; Sledge, E., Jr; Steppel-Resnick, J.; Turchin, A.; Brooks-Worrell, B.; Hampe, C.S.; Newgard, C.B.; Palmer, J.P.; Shojaie, A.; Higgins, J.; Fischer, L.; Golden, S.; Gonzalez, J.; Naik, A.; Walker, E.; Doner Lotenberg, L.; Gallivan, J.M.; Lim, J.; Tuncer, D.M.; Behringer-Massera, S. Optimization of metformin in the grade cohort: Effect on glycemia and body weight. Diabetes Care, 2020, 43(5), 940-947.
[http://dx.doi.org/10.2337/dc19-1769] [PMID: 32139384]
[23]
Hirst, J.A.; Farmer, A.J.; Ali, R.; Roberts, N.W.; Stevens, R.J. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care, 2012, 35(2), 446-454.
[http://dx.doi.org/10.2337/dc11-1465] [PMID: 22275444]
[24]
Moreno Juste, A.; Menditto, E.; Orlando, V.; Monetti, V.M.; Gimeno Miguel, A.; González Rubio, F.; Aza-Pascual-Salcedo, M.M.; Cahir, C.; Prados Torres, A.; Riccardi, G. Treatment patterns of diabetes in Italy: A population-based study. Front. Pharmacol., 2019, 10, 870.
[http://dx.doi.org/10.3389/fphar.2019.00870] [PMID: 31447672]
[25]
Luis-Lima, S.; Porrini, E. An overview of errors and flaws of estimated GFR versus true GFR in patients with diabetes mellitus. Nephron J., 2017, 136(4), 287-291.
[http://dx.doi.org/10.1159/000453531] [PMID: 27978513]

© 2024 Bentham Science Publishers | Privacy Policy