DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin–sulfonylurea dual therapy with inadequate control

IntroductionThis study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methodsWe assembled a retrospective coh...

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Published in:BMJ open diabetes research & care 2020-06, Vol.8 (1), p.e001346
Main Authors: Wong, Carlos K H, Man, Kenneth K C, Chan, Esther W Y, Wu, Tingting, Tse, Emily T Y, Wong, Ian C K, Lam, Cindy L K
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Language:English
Subjects:
Antidiabetics
Body mass index
Cancer
Cholesterol
Codes
Creatinine
Diabetes
Emerging Technologies, Pharmacology and Therapeutics
Fasting
Glucose
Insulin
Insulin resistance
Mortality
Patients
Physiology
Population
Triglycerides
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Man, Kenneth K C
Chan, Esther W Y
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Wong, Ian C K
Lam, Cindy L K
description IntroductionThis study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methodsWe assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.ResultsOver a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p
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Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.ResultsOver a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p&lt;0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.ConclusionsFor patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.</description><identifier>ISSN: 2052-4897</identifier><identifier>EISSN: 2052-4897</identifier><identifier>DOI: 10.1136/bmjdrc-2020-001346</identifier><identifier>PMID: 32532851</identifier><language>eng</language><publisher>London: BMJ Publishing Group LTD</publisher><subject>Antidiabetics ; Body mass index ; Cancer ; Cholesterol ; Codes ; Creatinine ; Diabetes ; Emerging Technologies, Pharmacology and Therapeutics ; Fasting ; Glucose ; Insulin ; Insulin resistance ; Mortality ; Patients ; Physiology ; Population ; Triglycerides</subject><ispartof>BMJ open diabetes research &amp; care, 2020-06, Vol.8 (1), p.e001346</ispartof><rights>Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2020 Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b511t-c1d5b2c1454d867bc60f2683c1a7a90890f0d24b46d6fe02d50ef6919ac723423</citedby><cites>FETCH-LOGICAL-b511t-c1d5b2c1454d867bc60f2683c1a7a90890f0d24b46d6fe02d50ef6919ac723423</cites><orcidid>0000-0002-7602-9470 ; 0000-0002-6895-6071 ; 0000-0001-8645-1942 ; 0000-0001-7409-9507 ; 0000-0001-7536-8481 ; 0000-0003-3609-5016 ; 0000-0001-8242-0014</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2433228705/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2433228705?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27526,27527,27901,27902,36989,36990,44566,53766,53768,75096,77570,77601</link.rule.ids></links><search><creatorcontrib>Wong, Carlos K H</creatorcontrib><creatorcontrib>Man, Kenneth K C</creatorcontrib><creatorcontrib>Chan, Esther W Y</creatorcontrib><creatorcontrib>Wu, Tingting</creatorcontrib><creatorcontrib>Tse, Emily T Y</creatorcontrib><creatorcontrib>Wong, Ian C K</creatorcontrib><creatorcontrib>Lam, Cindy L K</creatorcontrib><title>DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin–sulfonylurea dual therapy with inadequate control</title><title>BMJ open diabetes research &amp; care</title><description>IntroductionThis study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methodsWe assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.ResultsOver a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p&lt;0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.ConclusionsFor patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.</description><subject>Antidiabetics</subject><subject>Body mass index</subject><subject>Cancer</subject><subject>Cholesterol</subject><subject>Codes</subject><subject>Creatinine</subject><subject>Diabetes</subject><subject>Emerging Technologies, Pharmacology and Therapeutics</subject><subject>Fasting</subject><subject>Glucose</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Mortality</subject><subject>Patients</subject><subject>Physiology</subject><subject>Population</subject><subject>Triglycerides</subject><issn>2052-4897</issn><issn>2052-4897</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNks1u1TAQhSMEotWlL8DKEhsWDfg3cTZIqFCoVIkuYG1NbKfXl8S-tR3QZcU79BV4Mp4Eh1SIsmLlkc-Zb6zxqaqnBL8ghDUv-2lnoq4pprjGmDDePKiOKRa05rJrH_5VH1UnKe3wYmoIk-JxdcSoYFQKclz9eHN1xd0pylsH38LojPPWuOBtOkUhIufTPDqPwBsUXfqcUBiQBq_toqE9ZGd9Tuiry1uUD3uLKDIOepttQpMdR5fn0uNLnYcQJ-d_fr8tyCH4wzhHC8jMMJbpNsL-sGKcB2NvZsgW6eBzDOOT6tEAY7Ind-em-nT-9uPZ-_ryw7uLs9eXdS8IybUmRvRUEy64kU3b6wYPtJFME2ihw7LDAzaU97wxzWAxNQLboelIB7qljFO2qS5WrgmwU_voJogHFcCp3xchXiuI2enRKky5pkAkB0l4j0U3AGa8laQhywBZWK9W1n7uJ2t0WVOE8R70vuLdVl2HL6qlneBkATy_A8RwM9uU1eSSLisFb8OcFOWEdpI15U831bN_rLswR19WVVyMUSpbLIqLri4dQ0rRDn8eQ7BaMqXWTKklU2rNVGmq16ai_Y__F5Qu0Eg</recordid><startdate>20200611</startdate><enddate>20200611</enddate><creator>Wong, Carlos K H</creator><creator>Man, Kenneth K C</creator><creator>Chan, Esther W Y</creator><creator>Wu, Tingting</creator><creator>Tse, Emily T Y</creator><creator>Wong, Ian C K</creator><creator>Lam, Cindy L K</creator><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7602-9470</orcidid><orcidid>https://orcid.org/0000-0002-6895-6071</orcidid><orcidid>https://orcid.org/0000-0001-8645-1942</orcidid><orcidid>https://orcid.org/0000-0001-7409-9507</orcidid><orcidid>https://orcid.org/0000-0001-7536-8481</orcidid><orcidid>https://orcid.org/0000-0003-3609-5016</orcidid><orcidid>https://orcid.org/0000-0001-8242-0014</orcidid></search><sort><creationdate>20200611</creationdate><title>DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin–sulfonylurea dual therapy with inadequate control</title><author>Wong, Carlos K H ; 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care</jtitle><date>2020-06-11</date><risdate>2020</risdate><volume>8</volume><issue>1</issue><spage>e001346</spage><pages>e001346-</pages><issn>2052-4897</issn><eissn>2052-4897</eissn><abstract>IntroductionThis study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.Research design and methodsWe assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.ResultsOver a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p&lt;0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.ConclusionsFor patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.</abstract><cop>London</cop><pub>BMJ Publishing Group LTD</pub><pmid>32532851</pmid><doi>10.1136/bmjdrc-2020-001346</doi><orcidid>https://orcid.org/0000-0002-7602-9470</orcidid><orcidid>https://orcid.org/0000-0002-6895-6071</orcidid><orcidid>https://orcid.org/0000-0001-8645-1942</orcidid><orcidid>https://orcid.org/0000-0001-7409-9507</orcidid><orcidid>https://orcid.org/0000-0001-7536-8481</orcidid><orcidid>https://orcid.org/0000-0003-3609-5016</orcidid><orcidid>https://orcid.org/0000-0001-8242-0014</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antidiabetics
Body mass index
Cancer
Cholesterol
Codes
Creatinine
Diabetes
Emerging Technologies, Pharmacology and Therapeutics
Fasting
Glucose
Insulin
Insulin resistance
Mortality
Patients
Physiology
Population
Triglycerides
title DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 diabetes mellitus on metformin–sulfonylurea dual therapy with inadequate control
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