PMID- 34721294
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20220215
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network 
      Meta-Analysis.
PG  - 735824
LID - 10.3389/fendo.2021.735824 [doi]
LID - 735824
AB  - PURPOSE: Available data on the effects of anti-diabetic drugs on fracture risk 
      are contradictory. Therefore, our study aimed to analyze all available data on 
      the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus 
      (T2DM) patients. METHODS: Embase, Medline, ClinicalTrials.gov, and Cochrane 
      CENTRAL were searched for relevant trials. All data analyses were performed with 
      STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence 
      interval (CI) was calculated by combining data for the fracture effects of 
      anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) 
      inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 
      (GLP-1) receptor agonists, meglitinides, alpha-glucosidase inhibitors, 
      thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS: One hundred 
      seventeen eligible randomized controlled trials (RCTs) with 221,364 participants 
      were included in this study. Compared with placebo, trelagliptin (RR 3.51; 
      1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 
      0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other 
      medications were comparable in terms of their effects on fracture risk, and no 
      statistical significance was observed. In terms of fractures, voglibose (0.01%) 
      may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity 
      analysis results were consistent with those of the main analysis. No 
      statistically significant differences were observed in the regression 
      coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and 
      sex distribution (0.63; 0.15-1.56). CONCLUSIONS: We found varied results on the 
      association between the use of anti-diabetic drugs and fracture risk. 
      Specifically, trelagliptin raised the risk of fracture, whereas voglibose and 
      albiglutide showed benefit with statistical difference. Other drugs were 
      comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, 
      sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, 
      rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, 
      while others (such as dulaglutide, exenatide, liraglutide, semaglutide, 
      lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, 
      gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show 
      benefits. The risk of fracture was independent of age, sex distribution, and the 
      duration of exposure to anti-diabetic drugs. When developing individualized 
      treatment strategies, the clinical efficacy of anti-diabetic drugs must be 
      weighed against their benefits and risks brought about by individual differences 
      of patients. SYSTEMATIC REVIEW REGISTRATION: This Systematic Review was 
      prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, 
      registration number CRD42020189464).
CI  - Copyright (c) 2021 Zhang, Zheng, Yuan, Chen and Xie.
FAU - Zhang, Yu-Sheng
AU  - Zhang YS
AD  - Department of Pharmacy, The First People's Hospital of Foshan, Foshan, China.
FAU - Zheng, Yan-Dan
AU  - Zheng YD
AD  - Department of Clinical Laboratory, The First People's Hospital of Foshan, Foshan, 
      China.
FAU - Yuan, Yan
AU  - Yuan Y
AD  - Department of Pharmacy, The First People's Hospital of Foshan, Foshan, China.
FAU - Chen, Shi-Chun
AU  - Chen SC
AD  - Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, 
      China.
FAU - Xie, Bao-Cheng
AU  - Xie BC
AD  - Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, 
      China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20211014
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Hypoglycemic Agents)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Fractures, Bone/*etiology
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects/therapeutic use
MH  - Network Meta-Analysis
MH  - Risk Factors
PMC - PMC8553257
OTO - NOTNLM
OT  - anti-diabetic drug
OT  - fracture
OT  - meta-analysis
OT  - systematic review
OT  - type 2 diabetes mellitus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/02 06:00
MHDA- 2022/02/16 06:00
PMCR- 2021/01/01
CRDT- 2021/11/01 09:11
PHST- 2021/07/08 00:00 [received]
PHST- 2021/09/22 00:00 [accepted]
PHST- 2021/11/01 09:11 [entrez]
PHST- 2021/11/02 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.735824 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 Oct 14;12:735824. doi: 
      10.3389/fendo.2021.735824. eCollection 2021.