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Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

2023; Nature Portfolio; Volume: 3; Issue: 1 Linguagem: Inglês

10.1038/s43856-023-00359-w

2730-664X

Katherine Young, Eram Haider McInnes, Robert Massey, Anna R. Kahkoska, Scott J. Pilla, Sridharan Raghavan, Maggie A. Stanislawski, Deirdre K. Tobias, Andrew McGovern, Adem Y. Dawed, Angus G. Jones, Ewan R. Pearson, John Dennis, Deirdre K. Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L. Benham, Dhanasekaran Bodhini, Amy L. Clark, Kevin Colclough, Rosa Corcoy, Sara J. Cromer, Daisy Duan, Jamie L. Felton, Ellen C. Francis, Pieter Gillard, Véronique Gingras, Romy Gaillard, Eram Haider, Alice E. Hughes, Jennifer M. Iklé, Laura M. Jacobsen, Jarno L. T. Kettunen, Raymond J. Kreienkamp, Lee‐Ling Lim, Jonna M. E. Männistö, Robert Massey, Niamh‐Maire Mclennan, Rachel G. Miller, Mario Luca Morieri, Jasper Most, Rochelle N. Naylor, Bige Özkan, Kashyap Patel, Scott J. Pilla, Katsiaryna Prystupa, Sridaran Raghaven, Mary R. Rooney, Martin Schön, Zhila Semnani‐Azad, Magdalena Sevilla-González, Pernille Svalastoga, Wubet Worku Takele, Claudia H.T. Tam, Anne Cathrine B. Thuesen, Mustafa Tosur, Amelia S. Wallace, Caroline C. Wang, Jessie J. Wong, Jennifer M. Yamamoto, Katherine Young, Chloé Amouyal, Mette K. Andersen, Maxine P. Bonham, Mingling Chen, Feifei Cheng, Tinashe Chikowore, Sian C. Chivers, Christoffer Clemmensen, Dana Dabelea, Adem Y. Dawed, Aaron J. Deutsch, Laura T. Dickens, Linda A. DiMeglio, Monika Dudenhöffer‐Pfeifer, Carmella Evans‐Molina, María Mercè Fernández-Balsells, Hugo Fitipaldi, Stephanie L. Fitzpatrick, Stephen E. Gitelman, Mark O. Goodarzi, Jessica A. Grieger, Marta Guasch‐Ferré, Nahal Habibi, Torben Hansen, Chuiguo Huang, Arianna Harris-Kawano, Heba M. Ismail, Benjamin Hoag, Randi K. Johnson, Angus G. Jones, Robert W. Koivula, Aaron Leong, Gloria K. W. Leung, Ingrid Libman, Kai Liu, S. Alice Long, William L. Lowe, Robert W. Morton, Ayesha A. Motala, Suna Önengüt-Gümüşcü, James S. Pankow, Maleesa Pathirana, Sofia Pazmino, Dianna Perez, John R. Petrie, Camille E. Powe, Alejandra Quinteros, Rashmi Jain, Debashree Ray, Mathias Ried‐Larsen, Zeb Saeed, Vanessa Santhakumar, Sarah Kanbour, Sudipa Sarkar, Gabriela S. F. Monaco, Denise Scholtens, Elizabeth Selvin, Wayne Huey‐Herng Sheu, Cate Speake, Maggie A. Stanislawski, Nele Steenackers, Andrea K. Steck, Norbert Stefan, Julie Støy, Rachael W. Taylor, Sok Cin Tye, Gebresilasea Gendisha Ukke, Marzhan Urazbayeva, Bart Van der Schueren, Camille Vatier, John M. Wentworth, Wesley Hannah, Sara L. White, Gechang Yu, Yingchai Zhang, Shao J. Zhou, Jacques Beltrand, Michel Polak, Ingvild Aukrust, Elisa De Franco, Sarah E. Flanagan, Kristin A. Maloney, Andrew McGovern, Janne Molnes, Mariam Nakabuye, Pål R. Njølstad, Hugo Pomares‐Millan, Michele Provenzano, Cécile Saint‐Martin, Cuilin Zhang, Yeyi Zhu, Sungyoung Auh, Russell J. de Souza, Andrea J. Fawcett, Chandra Gruber, Eskedar Getie Mekonnen, Emily Mixter, Diana Sherifali, Robert H. Eckel, John J. Nolan, Louis H. Philipson, Rebecca J. Brown, Liana K. Billings, Kristen E. Boyle, Tina Costacou, John Dennis, José C. Florez, Anna L. Gloyn, Maria F. Gomez, Peter A. Gottlieb, Siri Atma W. Greeley, Kurt Griffin, Andrew T. Hattersley, Irl B. Hirsch, Marie‐France Hivert, Korey K. Hood, Jami L. Josefson, Soo Heon Kwak, Lori M. Laffel, Siew Lim, Ruth J. F. Loos, Ronald C.W., Chantal Mathieu, Nestoras Mathioudakis, James B. Meigs, Shivani Misra, Viswanathan Mohan, Rinki Murphy, Richard A. Oram, Katharine R. Owen, Susan E. Ozanne, Ewan R. Pearson, Wei Perng, Toni I. Pollin, Rodica Pop‐Busui, Richard E. Pratley, Leanne M. Redman, María J. Redondo, Rebecca M. Reynolds, Robert K. Semple, Jennifer L. Sherr, Emily K. Sims, Arianne Sweeting, Jaakko Tuomilehto, Miriam S. Udler, Kimberly K. Vesco, Tina Vilsbøll, Róbert Wágner, Stephen S. Rich, Paul W. Franks,

Diabetes Management and Research

Abstract Background A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Results Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Conclusions Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.