GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials
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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).
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.
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.
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.
KeywordsGLP-1 receptor agonists Cancer Meta-analysis Type 2 diabetes mellitus Randomized controlled trials
All authors collectively planned the study. C.C. designed the study and wrote the paper. C.C. and S.Y. collected, extracted, assessed, and analyzed the data. The first draft of the paper was written by C.C., and Z.Z. revised the paper. All authors reviewed the paper for intellectual content and approved the final version.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 3.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 CrossRefPubMedGoogle Scholar
- 5.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 CrossRefPubMedGoogle Scholar
- 6.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 CrossRefPubMedGoogle Scholar
- 9.D. Moher, B. Pham, A. Jones, D.J. Cook, A.R. Jadad, M. Moher, P. Tugwell, T.P. Klassen, Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 352(9128), 609–613 (1998). https://doi.org/10.1016/S0140-6736(98)01085-X CrossRefPubMedGoogle Scholar
- 11.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.M. Diamant, L. Van Gaal, B. Guerci, S. Stranks, J. Han, J. Malloy, M.K. Boardman, M.E. Trautmann, Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2(6), 464–473 (2014). https://doi.org/10.1016/S2213-8587(14)70029-4 CrossRefPubMedGoogle Scholar
- 13.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 CrossRefPubMedGoogle Scholar
- 14.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 CrossRefPubMedGoogle Scholar
- 15.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.M. Jaiswal, C.L. Martin, M.B. Brown, B. Callaghan, J.W. Albers, E.L. Feldman, R. Pop-Busui, Effects of exenatide on measures of diabetic neuropathy in subjects with type 2 diabetes: results from an 18-month proof-of-concept open-label randomized study. J. Diabetes Complicat. 29(8), 1287–1294 (2015). https://doi.org/10.1016/j.jdiacomp.2015.07.013 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.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 CrossRefPubMedGoogle Scholar
- 18.M.J. Davies, R. Bergenstal, B. Bode, R.F. Kushner, A. Lewin, T.V. Skjoth, A.H. Andreasen, C.B. Jensen, R.A. DeFronzo, N.N.S. Group, Efficacy of liraglutide for weight loss among patients with type 2 diabetes: The SCALE diabetes randomized clinical trial. JAMA 314(7), 687–699 (2015). https://doi.org/10.1001/jama.2015.9676 CrossRefPubMedGoogle Scholar
- 19.A. Garber, R.R. Henry, R. Ratner, P. Hale, C.T. Chang, B. Bode, L.-S. Group, Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes. Metab. 13(4), 348–356 (2011). https://doi.org/10.1111/j.1463-1326.2010.01356.x CrossRefPubMedPubMedCentralGoogle Scholar
- 20.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.K. Kaku, M.F. Rasmussen, P. Clauson, Y. Seino, Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes. Diabetes Obes. Metab. 12(4), 341–347 (2010). https://doi.org/10.1111/j.1463-1326.2009.01194.x CrossRefPubMedGoogle Scholar
- 22.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 CrossRefPubMedGoogle Scholar
- 23.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.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 CrossRefPubMedGoogle Scholar
- 25.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Y. Seino, M.F. Rasmussen, T. Nishida, K. Kaku, Efficacy and safety of the once-daily human GLP-1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes. Curr. Med. Res. Opin. 26(5), 1013–1022 (2010). https://doi.org/10.1185/03007991003672551 CrossRefPubMedGoogle Scholar
- 27.B. Ahren, A. Leguizamo Dimas, P. Miossec, S. Saubadu, R. Aronson, Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care 36(9), 2543–2550 (2013). https://doi.org/10.2337/dc12-2006 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.G.B. Bolli, M. Munteanu, S. Dotsenko, E. Niemoeller, G. Boka, Y. Wu, M. Hanefeld, Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet. Med. 31(2), 176–184 (2014). https://doi.org/10.1111/dme.12328 CrossRefPubMedGoogle Scholar
- 29.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 CrossRefPubMedGoogle Scholar
- 30.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 CrossRefPubMedGoogle Scholar
- 31.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.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 CrossRefPubMedGoogle Scholar
- 33.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 CrossRefPubMedGoogle Scholar
- 34.K. Kaku, Y. Yamada, H. Watada, A. Abiko, T. Nishida, J. Zacho, A. Kiyosue, Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: a randomized trial. Diabetes Obes. Metab. 20(5), 1202–1212 (2018). https://doi.org/10.1111/dom.13218 CrossRefPubMedPubMedCentralGoogle Scholar
- 35.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 CrossRefPubMedGoogle Scholar
- 36.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 CrossRefPubMedGoogle Scholar
- 37.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 CrossRefPubMedGoogle Scholar
- 38.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 CrossRefPubMedGoogle Scholar
- 39.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 CrossRefPubMedGoogle Scholar
- 40.L.A. Leiter, J.L. Gross, F. Chow, D. Miller, S. Johnson, B. Ahren, H.S. Group, Once weekly glucagon-like peptide-1 receptor agonist albiglutide vs. prandial insulin added to basal insulin in patients with type 2 diabetes mellitus: Results over 52 weeks. J. Diabetes Complicat. 31(8), 1283–1285 (2017). https://doi.org/10.1016/j.jdiacomp.2017.05.010 CrossRefPubMedGoogle Scholar
- 41.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 CrossRefPubMedGoogle Scholar
- 42.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 CrossRefPubMedGoogle Scholar
- 43.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 CrossRefPubMedGoogle Scholar
- 44.F. Giorgino, M. Benroubi, J.H. Sun, A.G. Zimmermann, V. Pechtner, Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care 38(12), 2241–2249 (2015). https://doi.org/10.2337/dc14-1625 CrossRefPubMedGoogle Scholar
- 45.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 CrossRefPubMedGoogle Scholar
- 46.G. Umpierrez, S. Tofe Povedano, F. Perez Manghi, L. Shurzinske, V. Pechtner, Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 37(8), 2168–2176 (2014). https://doi.org/10.2337/dc13-2759 CrossRefPubMedGoogle Scholar
- 47.R.S. Weinstock, B. Guerci, G. Umpierrez, M.A. Nauck, Z. Skrivanek, Z. Milicevic, Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes. Metab. 17(9), 849–858 (2015). https://doi.org/10.1111/dom.12479 CrossRefPubMedPubMedCentralGoogle Scholar
- 49.I. Martin-Lacave, R. Bernab, C. Sampedro, E. Conde, J.M. Fernandez-Santos, M.V. San Martin, A. Beato, H. Galera-Davidson, Correlation between gender and spontaneous C-cell tumors in the thyroid gland of the Wistar rat. Cell Tissue Res. 297(3), 451–457 (1999). https://doi.org/10.1007/s004410051371 CrossRefPubMedGoogle Scholar
- 51.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 CrossRefPubMedGoogle Scholar
- 52.A. Noone, N. Howlader, M. Krapcho. SEER Cancer Statistics Review, 1975–2015 (National Cancer Institute, Bethesda, MD, 2018), https://seer.cancer.gov/csr/1975_2015/. Accessed 22 Oct 2018.
- 55.A.E. Butler, M. Campbell-Thompson, T. Gurlo, D.W. Dawson, M. Atkinson, P.C. Butler, Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 62(7), 2595–2604 (2013). https://doi.org/10.2337/db12-1686 CrossRefPubMedPubMedCentralGoogle Scholar
- 57.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 58.D. Abrahami, A. Douros, H. Yin, O.H. Yu, J.L. Faillie, F. Montastruc, R.W. Platt, N. Bouganim, L. Azoulay, Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study. BMJ 363, k4880 (2018). https://doi.org/10.1136/bmj.k4880 CrossRefPubMedPubMedCentralGoogle Scholar
- 60.B.M. Hicks, H. Yin, O.H. Yu, M.N. Pollak, R.W. Platt, L. Azoulay, Glucagon-like peptide-1 analogues and risk of breast cancer in women with type 2 diabetes: population based cohort study using the UK Clinical Practice Research Datalink. BMJ 355, i5340 (2016). https://doi.org/10.1136/bmj.i5340 CrossRefPubMedGoogle Scholar
- 61.H. Zhao, R. Wei, L. Wang, Q. Tian, M. Tao, J. Ke, Y. Liu, W. Hou, L. Zhang, J. Yang, T. Hong, Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner. Am. J. Physiol. Endocrinol. Metab. 306(12), E1431–E1441 (2014). https://doi.org/10.1152/ajpendo.00017.2014 CrossRefPubMedGoogle Scholar