PMID- 32532851
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 2052-4897 (Electronic)
IS  - 2052-4897 (Linking)
VI  - 8
IP  - 1
DP  - 2020 Jun
TI  - DPP4i, thiazolidinediones, or insulin and risks of cancer in patients with type 2 
      diabetes mellitus on metformin-sulfonylurea dual therapy with inadequate control.
LID - 10.1136/bmjdrc-2020-001346 [doi]
LID - e001346
AB  - INTRODUCTION: This 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 METHODS: We 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. RESULTS: Over 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<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. CONCLUSIONS: For 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.
CI  - (c) 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.
FAU - Wong, Carlos K H
AU  - Wong CKH
AUID- ORCID: 0000-0002-6895-6071
AD  - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, 
      The University of Hong Kong, Hong Kong SAR, China carlosho@hku.hk.
FAU - Man, Kenneth K C
AU  - Man KKC
AUID- ORCID: 0000-0001-8645-1942
AD  - Centre for Safe Medication Practice and Research, Department of Pharmacology and 
      Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
AD  - Research Department of Policy and Practice, University College London School of 
      Pharmacy, London, UK.
FAU - Chan, Esther W Y
AU  - Chan EWY
AUID- ORCID: 0000-0002-7602-9470
AD  - Centre for Safe Medication Practice and Research, Department of Pharmacology and 
      Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
FAU - Wu, Tingting
AU  - Wu T
AUID- ORCID: 0000-0003-3609-5016
AD  - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, 
      The University of Hong Kong, Hong Kong SAR, China.
FAU - Tse, Emily T Y
AU  - Tse ETY
AUID- ORCID: 0000-0001-7409-9507
AD  - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, 
      The University of Hong Kong, Hong Kong SAR, China.
FAU - Wong, Ian C K
AU  - Wong ICK
AUID- ORCID: 0000-0001-8242-0014
AD  - Centre for Safe Medication Practice and Research, Department of Pharmacology and 
      Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
AD  - Research Department of Policy and Practice, University College London School of 
      Pharmacy, London, UK.
FAU - Lam, Cindy L K
AU  - Lam CLK
AUID- ORCID: 0000-0001-7536-8481
AD  - Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, 
      The University of Hong Kong, Hong Kong SAR, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BMJ Open Diabetes Res Care
JT  - BMJ open diabetes research & care
JID - 101641391
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Thiazolidinediones)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/drug therapy/epidemiology
MH  - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - Insulin/adverse effects
MH  - *Metformin/adverse effects
MH  - *Neoplasms/chemically induced/epidemiology
MH  - Retrospective Studies
MH  - *Thiazolidinediones/adverse effects
MH  - Treatment Outcome
PMC - PMC7295418
OTO - NOTNLM
OT  - cancer
OT  - insulin
OT  - thiazolidinediones
OT  - type 2 diabetes
COIS- Competing interests: CKHW reports receipt of research funding from the EuroQoL 
      Group Research Foundation, the Hong Kong Research Grants Council, and the Hong 
      Kong Health and Medical Research Fund. KKCM reports receipt of CW Maplethorpe 
      Fellowship and personal fee from IQVIA Ltd. EWYC reports receipt of research 
      funding from Bristol-Myers Squibb, Pfizer, Janssen, Takeda Pharmaceuticals, the 
      Hong Kong Beat Drugs Fund Association, the Hong Kong Research Grants Council, and 
      the Hong Kong Health and Medical Research Fund. ICKW reports receipt of research 
      funding from Bristol-Myers Squibb, Pfizer, Janssen, the Hong Kong Research Grants 
      Council, and the Hong Kong Health and Medical Research Fund. CLKL reports receipt 
      of research funding from the Hong Kong Research Grants Council, the Hong Kong 
      Health and Medical Research Fund, and the Kerry Group and Kouk Foundation Endowed 
      Primary Care Research Fund of the University of Hong Kong. No other disclosures 
      were reported.
EDAT- 2020/06/14 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/06/11
CRDT- 2020/06/14 06:00
PHST- 2020/03/10 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/06/14 06:00 [entrez]
PHST- 2020/06/14 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/11 00:00 [pmc-release]
AID - 8/1/e001346 [pii]
AID - bmjdrc-2020-001346 [pii]
AID - 10.1136/bmjdrc-2020-001346 [doi]
PST - ppublish
SO  - BMJ Open Diabetes Res Care. 2020 Jun;8(1):e001346. doi: 
      10.1136/bmjdrc-2020-001346.