Skip to main content
Top
Published in: Endocrine 2/2019

01-11-2019 | Albiglutide | Meta-Analysis

GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials

Authors: Chuqing Cao, Shuting Yang, Zhiguang Zhou

Published in: Endocrine | Issue 2/2019

Login to get access

Abstract

Purpose

Some preliminary studies reported a link between GLP-1 receptor agonists (GLP-1RAs) and thyroid/pancreatic neoplasms, while its human relevance remained undetermined. The present meta-analysis was performed to collect information on cancers associated with GLP-1RAs in patients with type 2 diabetes mellitus (T2DM).

Methods

Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and ClinicalTrials.gov were extensively searched to identify randomized controlled trials that reported cancer events in T2DM patients treated with GLP-1RAs for at least 52 weeks, up to March 18, 2019. Odds ratio (OR) with 95% Confidence Interval (CI) was calculated for overall cancer (primary outcome), thyroid and pancreatic cancer.

Results

A total of 37 eligible trials were identified. The OR for overall cancer associated with GLP-1RAs was 1.03 (95% CI 0.95–1.12; p = 0.41) compared with comparators. Subgroup analyses showed that treatment with albiglutide was associated with a lower risk of overall cancer (OR 0.76 [95% CI 0.60–0.97]; p = 0.03), and no elevated risk of overall cancer was identified for other GLP-1RAs. No significant differences in the risks of thyroid nor pancreatic cancer were disclosed between GLP-1RAs and comparators.

Conclusions

This meta-analysis did not suggest any increased risk of cancers associated with GLP-1RAs use in T2DM. The reduction in the risk of overall cancer associated with albiglutide needs to be examined further.
Appendix
Available only for authorised users
Literature
3.
go back to reference X. Michelet, L. Dyck, A. Hogan, R.M. Loftus, D. Duquette, K. Wei, S. Beyaz, A. Tavakkoli, C. Foley, R. Donnelly, C. O'Farrelly, M. Raverdeau, A. Vernon, W. Pettee, D. O'Shea, B.S. Nikolajczyk, K.H.G. Mills, M.B. Brenner, D. Finlay, L. Lynch, Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat. Immunol. 19(12), 1330–1340 (2018). https://doi.org/10.1038/s41590-018-0251-7 CrossRefPubMed X. Michelet, L. Dyck, A. Hogan, R.M. Loftus, D. Duquette, K. Wei, S. Beyaz, A. Tavakkoli, C. Foley, R. Donnelly, C. O'Farrelly, M. Raverdeau, A. Vernon, W. Pettee, D. O'Shea, B.S. Nikolajczyk, K.H.G. Mills, M.B. Brenner, D. Finlay, L. Lynch, Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat. Immunol. 19(12), 1330–1340 (2018). https://​doi.​org/​10.​1038/​s41590-018-0251-7 CrossRefPubMed
5.
go back to reference Y. Zhao, L. Yang, Y. Xiang, L. Liu, G. Huang, Z. Long, X. Li, R.D. Leslie, X. Wang, Z. Zhou, Dipeptidyl peptidase 4 inhibitor sitagliptin maintains beta-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. J. Clin. Endocrinol. Metab. 99(5), E876–E880 (2014). https://doi.org/10.1210/jc.2013-3633 CrossRefPubMed Y. Zhao, L. Yang, Y. Xiang, L. Liu, G. Huang, Z. Long, X. Li, R.D. Leslie, X. Wang, Z. Zhou, Dipeptidyl peptidase 4 inhibitor sitagliptin maintains beta-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. J. Clin. Endocrinol. Metab. 99(5), E876–E880 (2014). https://​doi.​org/​10.​1210/​jc.​2013-3633 CrossRefPubMed
6.
go back to reference L. Bjerre Knudsen, L.W. Madsen, S. Andersen, K. Almholt, A.S. de Boer, D.J. Drucker, C. Gotfredsen, F.L. Egerod, A.C. Hegelund, H. Jacobsen, S.D. Jacobsen, A.C. Moses, A.M. Molck, H.S. Nielsen, J. Nowak, H. Solberg, T.D. Thi, M. Zdravkovic, U. Moerch, Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 151(4), 1473–1486 (2010). https://doi.org/10.1210/en.2009-1272 CrossRefPubMed L. Bjerre Knudsen, L.W. Madsen, S. Andersen, K. Almholt, A.S. de Boer, D.J. Drucker, C. Gotfredsen, F.L. Egerod, A.C. Hegelund, H. Jacobsen, S.D. Jacobsen, A.C. Moses, A.M. Molck, H.S. Nielsen, J. Nowak, H. Solberg, T.D. Thi, M. Zdravkovic, U. Moerch, Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 151(4), 1473–1486 (2010). https://​doi.​org/​10.​1210/​en.​2009-1272 CrossRefPubMed
10.
go back to reference A.R. Jadad, R.A. Moore, D. Carroll, C. Jenkinson, D.J. Reynolds, D.J. Gavaghan, H.J. McQuay, Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin. Trials 17(1), 1–12 (1996)CrossRef A.R. Jadad, R.A. Moore, D. Carroll, C. Jenkinson, D.J. Reynolds, D.J. Gavaghan, H.J. McQuay, Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin. Trials 17(1), 1–12 (1996)CrossRef
11.
go back to reference M.C. Bunck, M. Diamant, A. Corner, B. Eliasson, J.L. Malloy, R.M. Shaginian, W. Deng, D.M. Kendall, M.R. Taskinen, U. Smith, H. Yki-Jarvinen, R.J. Heine, One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 32(5), 762–768 (2009). https://doi.org/10.2337/dc08-1797 CrossRefPubMedPubMedCentral M.C. Bunck, M. Diamant, A. Corner, B. Eliasson, J.L. Malloy, R.M. Shaginian, W. Deng, D.M. Kendall, M.R. Taskinen, U. Smith, H. Yki-Jarvinen, R.J. Heine, One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 32(5), 762–768 (2009). https://​doi.​org/​10.​2337/​dc08-1797 CrossRefPubMedPubMedCentral
13.
go back to reference B. Gallwitz, J. Guzman, F. Dotta, B. Guerci, R. Simo, B.R. Basson, A. Festa, J. Kiljanski, H. Sapin, M. Trautmann, G. Schernthaner, Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial. Lancet 379(9833), 2270–2278 (2012). https://doi.org/10.1016/S0140-6736(12)60479-6 CrossRefPubMed B. Gallwitz, J. Guzman, F. Dotta, B. Guerci, R. Simo, B.R. Basson, A. Festa, J. Kiljanski, H. Sapin, M. Trautmann, G. Schernthaner, Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial. Lancet 379(9833), 2270–2278 (2012). https://​doi.​org/​10.​1016/​S0140-6736(12)60479-6 CrossRefPubMed
14.
go back to reference R.R. Holman, M.A. Bethel, R.J. Mentz, V.P. Thompson, Y. Lokhnygina, J.B. Buse, J.C. Chan, J. Choi, S.M. Gustavson, N. Iqbal, A.P. Maggioni, S.P. Marso, P. Ohman, N.J. Pagidipati, N. Poulter, A. Ramachandran, B. Zinman, A.F. Hernandez, E.S. Group, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 377(13), 1228–1239 (2017). https://doi.org/10.1056/NEJMoa1612917 CrossRefPubMed R.R. Holman, M.A. Bethel, R.J. Mentz, V.P. Thompson, Y. Lokhnygina, J.B. Buse, J.C. Chan, J. Choi, S.M. Gustavson, N. Iqbal, A.P. Maggioni, S.P. Marso, P. Ohman, N.J. Pagidipati, N. Poulter, A. Ramachandran, B. Zinman, A.F. Hernandez, E.S. Group, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 377(13), 1228–1239 (2017). https://​doi.​org/​10.​1056/​NEJMoa1612917 CrossRefPubMed
15.
go back to reference S.A. Jabbour, J.P. Frias, E. Hardy, A. Ahmed, H. Wang, P. Ohman, C. Guja, Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled trial. Diabetes Care 41(10), 2136–2146 (2018). https://doi.org/10.2337/dc18-0680 CrossRefPubMedPubMedCentral S.A. Jabbour, J.P. Frias, E. Hardy, A. Ahmed, H. Wang, P. Ohman, C. Guja, Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled trial. Diabetes Care 41(10), 2136–2146 (2018). https://​doi.​org/​10.​2337/​dc18-0680 CrossRefPubMedPubMedCentral
17.
go back to reference M.A. Nauck, S. Duran, D. Kim, D. Johns, J. Northrup, A. Festa, R. Brodows, M. Trautmann, A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50(2), 259–267 (2007). https://doi.org/10.1007/s00125-006-0510-2 CrossRefPubMed M.A. Nauck, S. Duran, D. Kim, D. Johns, J. Northrup, A. Festa, R. Brodows, M. Trautmann, A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50(2), 259–267 (2007). https://​doi.​org/​10.​1007/​s00125-006-0510-2 CrossRefPubMed
18.
20.
go back to reference S.C. Gough, B.W. Bode, V.C. Woo, H.W. Rodbard, S. Linjawi, M. Zacho, P.D. Reiter, J.B. Buse, One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes. Metab. 17(10), 965–973 (2015). https://doi.org/10.1111/dom.12498 CrossRefPubMedPubMedCentral S.C. Gough, B.W. Bode, V.C. Woo, H.W. Rodbard, S. Linjawi, M. Zacho, P.D. Reiter, J.B. Buse, One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes. Metab. 17(10), 965–973 (2015). https://​doi.​org/​10.​1111/​dom.​12498 CrossRefPubMedPubMedCentral
22.
go back to reference K. Kaku, A. Kiyosue, Y. Ono, T. Shiraiwa, S. Kaneko, K. Nishijima, H. Bosch-Traberg, Y. Seino, Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: a randomized, 52-week, open-label, parallel-group trial. J. Diabetes Investig. 7(1), 76–84 (2016). https://doi.org/10.1111/jdi.12367 CrossRefPubMed K. Kaku, A. Kiyosue, Y. Ono, T. Shiraiwa, S. Kaneko, K. Nishijima, H. Bosch-Traberg, Y. Seino, Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: a randomized, 52-week, open-label, parallel-group trial. J. Diabetes Investig. 7(1), 76–84 (2016). https://​doi.​org/​10.​1111/​jdi.​12367 CrossRefPubMed
23.
go back to reference S.P. Marso, G.H. Daniels, K. Brown-Frandsen, P. Kristensen, J.F. Mann, M.A. Nauck, S.E. Nissen, S. Pocock, N.R. Poulter, L.S. Ravn, W.M. Steinberg, M. Stockner, B. Zinman, R.M. Bergenstal, J.B. Buse; L.S. Committee, L.T. Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375(4), 311–322 (2016). https://doi.org/10.1056/NEJMoa1603827 CrossRefPubMedPubMedCentral S.P. Marso, G.H. Daniels, K. Brown-Frandsen, P. Kristensen, J.F. Mann, M.A. Nauck, S.E. Nissen, S. Pocock, N.R. Poulter, L.S. Ravn, W.M. Steinberg, M. Stockner, B. Zinman, R.M. Bergenstal, J.B. Buse; L.S. Committee, L.T. Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375(4), 311–322 (2016). https://​doi.​org/​10.​1056/​NEJMoa1603827 CrossRefPubMedPubMedCentral
24.
go back to reference M. Nauck, A. Frid, K. Hermansen, A.B. Thomsen, M. During, N. Shah, T. Tankova, I. Mitha, D.R. Matthews, Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes. Metab. 15(3), 204–212 (2013). https://doi.org/10.1111/dom.12012 CrossRefPubMed M. Nauck, A. Frid, K. Hermansen, A.B. Thomsen, M. During, N. Shah, T. Tankova, I. Mitha, D.R. Matthews, Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes. Metab. 15(3), 204–212 (2013). https://​doi.​org/​10.​1111/​dom.​12012 CrossRefPubMed
25.
go back to reference R. Pratley, M. Nauck, T. Bailey, E. Montanya, R. Cuddihy, S. Filetti, A. Garber, A.B. Thomsen, H. Hartvig, M. Davies, L.-D.-S Group, One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J. Clin. Pract. 65(4), 397–407 (2011). https://doi.org/10.1111/j.1742-1241.2011.02656.x CrossRefPubMedPubMedCentral R. Pratley, M. Nauck, T. Bailey, E. Montanya, R. Cuddihy, S. Filetti, A. Garber, A.B. Thomsen, H. Hartvig, M. Davies, L.-D.-S Group, One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J. Clin. Pract. 65(4), 397–407 (2011). https://​doi.​org/​10.​1111/​j.​1742-1241.​2011.​02656.​x CrossRefPubMedPubMedCentral
28.
29.
go back to reference M.A. Pfeffer, B. Claggett, R. Diaz, K. Dickstein, H.C. Gerstein, L.V. Kober, F.C. Lawson, L. Ping, X. Wei, E.F. Lewis, A.P. Maggioni, J.J. McMurray, J.L. Probstfield, M.C. Riddle, S.D. Solomon, J.C. Tardif, E. Investigators, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373(23), 2247–2257 (2015). https://doi.org/10.1056/NEJMoa1509225 CrossRefPubMed M.A. Pfeffer, B. Claggett, R. Diaz, K. Dickstein, H.C. Gerstein, L.V. Kober, F.C. Lawson, L. Ping, X. Wei, E.F. Lewis, A.P. Maggioni, J.J. McMurray, J.L. Probstfield, M.C. Riddle, S.D. Solomon, J.C. Tardif, E. Investigators, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373(23), 2247–2257 (2015). https://​doi.​org/​10.​1056/​NEJMoa1509225 CrossRefPubMed
30.
go back to reference M. Pinget, R. Goldenberg, E. Niemoeller, I. Muehlen-Bartmer, H. Guo, R. Aronson, Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes. Metab. 15(11), 1000–1007 (2013). https://doi.org/10.1111/dom.12121 CrossRefPubMed M. Pinget, R. Goldenberg, E. Niemoeller, I. Muehlen-Bartmer, H. Guo, R. Aronson, Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes. Metab. 15(11), 1000–1007 (2013). https://​doi.​org/​10.​1111/​dom.​12121 CrossRefPubMed
31.
go back to reference M.C. Riddle, R. Aronson, P. Home, M. Marre, E. Niemoeller, P. Miossec, L. Ping, J. Ye, J. Rosenstock, Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care 36(9), 2489–2496 (2013). https://doi.org/10.2337/dc12-2454 CrossRefPubMedPubMedCentral M.C. Riddle, R. Aronson, P. Home, M. Marre, E. Niemoeller, P. Miossec, L. Ping, J. Ye, J. Rosenstock, Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care 36(9), 2489–2496 (2013). https://​doi.​org/​10.​2337/​dc12-2454 CrossRefPubMedPubMedCentral
32.
go back to reference J. Rosenstock, M. Hanefeld, P. Shamanna, K.W. Min, G. Boka, P. Miossec, T. Zhou, I. Muehlen-Bartmer, R.E. Ratner, Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J. Diabetes Complicat. 28(3), 386–392 (2014). https://doi.org/10.1016/j.jdiacomp.2014.01.012 CrossRefPubMed J. Rosenstock, M. Hanefeld, P. Shamanna, K.W. Min, G. Boka, P. Miossec, T. Zhou, I. Muehlen-Bartmer, R.E. Ratner, Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). J. Diabetes Complicat. 28(3), 386–392 (2014). https://​doi.​org/​10.​1016/​j.​jdiacomp.​2014.​01.​012 CrossRefPubMed
33.
go back to reference B. Ahren, L. Masmiquel, H. Kumar, M. Sargin, J.D. Karsbol, S.H. Jacobsen, F. Chow, Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 5(5), 341–354 (2017). https://doi.org/10.1016/S2213-8587(17)30092-X CrossRefPubMed B. Ahren, L. Masmiquel, H. Kumar, M. Sargin, J.D. Karsbol, S.H. Jacobsen, F. Chow, Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 5(5), 341–354 (2017). https://​doi.​org/​10.​1016/​S2213-8587(17)30092-X CrossRefPubMed
35.
go back to reference S.P. Marso, S.C. Bain, A. Consoli, F.G. Eliaschewitz, E. Jodar, L.A. Leiter, I. Lingvay, J. Rosenstock, J. Seufert, M.L. Warren, V. Woo, O. Hansen, A.G. Holst, J. Pettersson, T. Vilsboll; S.-. Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375(19), 1834–1844 (2016). https://doi.org/10.1056/NEJMoa1607141 CrossRefPubMed S.P. Marso, S.C. Bain, A. Consoli, F.G. Eliaschewitz, E. Jodar, L.A. Leiter, I. Lingvay, J. Rosenstock, J. Seufert, M.L. Warren, V. Woo, O. Hansen, A.G. Holst, J. Pettersson, T. Vilsboll; S.-. Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375(19), 1834–1844 (2016). https://​doi.​org/​10.​1056/​NEJMoa1607141 CrossRefPubMed
36.
go back to reference B. Ahren, S.L. Johnson, M. Stewart, D.T. Cirkel, F. Yang, C. Perry, M.N. Feinglos, H.S. Group, HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care 37(8), 2141–2148 (2014). https://doi.org/10.2337/dc14-0024 CrossRefPubMed B. Ahren, S.L. Johnson, M. Stewart, D.T. Cirkel, F. Yang, C. Perry, M.N. Feinglos, H.S. Group, HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care 37(8), 2141–2148 (2014). https://​doi.​org/​10.​2337/​dc14-0024 CrossRefPubMed
37.
go back to reference A.F. Hernandez, J.B. Green, S. Janmohamed, R.B. D′Agostino Sr., C.B. Granger, N.P. Jones, L.A. Leiter, A.E. Rosenberg, K.N. Sigmon, M.C. Somerville, K.M. Thorpe, J.J.V. McMurray, S. Del Prato; c. Harmony Outcomes, investigators, Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392(10157), 1519–1529 (2018). https://doi.org/10.1016/S0140-6736(18)32261-X CrossRefPubMed A.F. Hernandez, J.B. Green, S. Janmohamed, R.B. D′Agostino Sr., C.B. Granger, N.P. Jones, L.A. Leiter, A.E. Rosenberg, K.N. Sigmon, M.C. Somerville, K.M. Thorpe, J.J.V. McMurray, S. Del Prato; c. Harmony Outcomes, investigators, Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392(10157), 1519–1529 (2018). https://​doi.​org/​10.​1016/​S0140-6736(18)32261-X CrossRefPubMed
38.
go back to reference P.D. Home, P. Shamanna, M. Stewart, F. Yang, M. Miller, C. Perry, M.C. Carr, Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5. Diabetes Obes. Metab. 17(2), 179–187 (2015). https://doi.org/10.1111/dom.12414 CrossRefPubMed P.D. Home, P. Shamanna, M. Stewart, F. Yang, M. Miller, C. Perry, M.C. Carr, Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5. Diabetes Obes. Metab. 17(2), 179–187 (2015). https://​doi.​org/​10.​1111/​dom.​12414 CrossRefPubMed
39.
go back to reference L.A. Leiter, M.C. Carr, M. Stewart, A. Jones-Leone, R. Scott, F. Yang, Y. Handelsman, Efficacy and safety of the once-weekly GLP-1 receptor agonist albiglutide versus sitagliptin in patients with type 2 diabetes and renal impairment: a randomized phase III study. Diabetes Care 37(10), 2723–2730 (2014). https://doi.org/10.2337/dc13-2855 CrossRefPubMed L.A. Leiter, M.C. Carr, M. Stewart, A. Jones-Leone, R. Scott, F. Yang, Y. Handelsman, Efficacy and safety of the once-weekly GLP-1 receptor agonist albiglutide versus sitagliptin in patients with type 2 diabetes and renal impairment: a randomized phase III study. Diabetes Care 37(10), 2723–2730 (2014). https://​doi.​org/​10.​2337/​dc13-2855 CrossRefPubMed
41.
go back to reference M.A. Nauck, M.W. Stewart, C. Perkins, A. Jones-Leone, F. Yang, C. Perry, R.R. Reinhardt, M. Rendell, Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetologia 59(2), 266–274 (2016). https://doi.org/10.1007/s00125-015-3795-1 CrossRefPubMed M.A. Nauck, M.W. Stewart, C. Perkins, A. Jones-Leone, F. Yang, C. Perry, R.R. Reinhardt, M. Rendell, Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetologia 59(2), 266–274 (2016). https://​doi.​org/​10.​1007/​s00125-015-3795-1 CrossRefPubMed
42.
go back to reference P.N. Weissman, M.C. Carr, J. Ye, D.T. Cirkel, M. Stewart, C. Perry, R. Pratley, HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea. Diabetologia 57(12), 2475–2484 (2014). https://doi.org/10.1007/s00125-014-3360-3 CrossRefPubMed P.N. Weissman, M.C. Carr, J. Ye, D.T. Cirkel, M. Stewart, C. Perry, R. Pratley, HARMONY 4: randomised clinical trial comparing once-weekly albiglutide and insulin glargine in patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea. Diabetologia 57(12), 2475–2484 (2014). https://​doi.​org/​10.​1007/​s00125-014-3360-3 CrossRefPubMed
43.
go back to reference L. Blonde, J. Jendle, J. Gross, V. Woo, H. Jiang, J.L. Fahrbach, Z. Milicevic, Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet 385(9982), 2057–2066 (2015). https://doi.org/10.1016/S0140-6736(15)60936-9 CrossRefPubMed L. Blonde, J. Jendle, J. Gross, V. Woo, H. Jiang, J.L. Fahrbach, Z. Milicevic, Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet 385(9982), 2057–2066 (2015). https://​doi.​org/​10.​1016/​S0140-6736(15)60936-9 CrossRefPubMed
44.
45.
go back to reference K.R. Tuttle, M.C. Lakshmanan, B. Rayner, R.S. Busch, A.G. Zimmermann, D.B. Woodward, F.T. Botros, Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 6(8), 605–617 (2018). https://doi.org/10.1016/S2213-8587(18)30104-9 CrossRefPubMed K.R. Tuttle, M.C. Lakshmanan, B. Rayner, R.S. Busch, A.G. Zimmermann, D.B. Woodward, F.T. Botros, Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 6(8), 605–617 (2018). https://​doi.​org/​10.​1016/​S2213-8587(18)30104-9 CrossRefPubMed
51.
go back to reference L. Hegedus, A.C. Moses, M. Zdravkovic, T. Le Thi, G.H. Daniels, GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J. Clin. Endocrinol. Metab. 96(3), 853–860 (2011). https://doi.org/10.1210/jc.2010-2318 CrossRefPubMed L. Hegedus, A.C. Moses, M. Zdravkovic, T. Le Thi, G.H. Daniels, GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J. Clin. Endocrinol. Metab. 96(3), 853–860 (2011). https://​doi.​org/​10.​1210/​jc.​2010-2318 CrossRefPubMed
55.
57.
go back to reference L. Azoulay, K.B. Filion, R.W. Platt, M. Dahl, C.R. Dormuth, K.K. Clemens, M. Durand, D.N. Juurlink, L.E. Targownik, T.C. Turin, J.M. Paterson, P. Ernst; I. Canadian Network for Observational Drug Effect Studies, Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ 352, i581 (2016). https://doi.org/10.1136/bmj.i581 CrossRefPubMedPubMedCentral L. Azoulay, K.B. Filion, R.W. Platt, M. Dahl, C.R. Dormuth, K.K. Clemens, M. Durand, D.N. Juurlink, L.E. Targownik, T.C. Turin, J.M. Paterson, P. Ernst; I. Canadian Network for Observational Drug Effect Studies, Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ 352, i581 (2016). https://​doi.​org/​10.​1136/​bmj.​i581 CrossRefPubMedPubMedCentral
60.
61.
Metadata
Title
GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials
Authors
Chuqing Cao
Shuting Yang
Zhiguang Zhou
Publication date
01-11-2019
Publisher
Springer US
Published in
Endocrine / Issue 2/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-02055-z

Other articles of this Issue 2/2019

Endocrine 2/2019 Go to the issue