PMID- 36119737
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220920
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and 
      trial sequential analysis.
PG  - 990182
LID - 10.3389/fcvm.2022.990182 [doi]
LID - 990182
AB  - OBJECTIVE: The purpose of this study is to evaluate the optimal dose of 
      tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by 
      meta-analysis and trial sequential analysis (TSA). METHODS: Clinical trials of 
      TZP for T2DM were obtained by searching 8 databases with a time limit from 
      database creation to May 2022. Mean differences (MD) and 95% confidence intervals 
      (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were 
      used for dichotomous variables. RESULTS: Compared with TZP 5 mg, meta-analysis 
      showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c 
      (HbA1c) (MD -0.24, 95%CI -0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) 
      (MD -5.82, 95%CI -8.35~-3.28, P < 0.00001) and weight (MD -2.47, 95%CI 
      -2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD -0.37, 
      95%CI -0.44~-0.29, P < 0.00001), FSG (MD -8.52, 95%CI -11.07~-5.98, P < 0.00001) 
      and weight (MD -4.63, 95%CI -5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, 
      TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), 
      FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI 
      -2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the 
      current information set were conclusive, except for the FSG of "TZP 15 mg vs. TZP 
      10 mg". In terms of safety endpoints, meta-analysis revealed that there was no 
      significant difference in the serious adverse events (AEs), major adverse 
      cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and 
      hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg 
      increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and 
      gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg 
      increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no 
      significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 
      mg. The TSA demonstrated that the total AEs of "TZP 15 mg vs. TZP 5 mg" were 
      conclusive. CONCLUSIONS: TZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering 
      glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of 
      safety. On this basis, we recommend TZP 5 mg as the first-choice dose for 
      patients with T2DM to minimize AEs while reducing glycemia and weight. If 
      patients cannot effectively control their glycemia after taking TZP 5 mg, it is 
      recommended to take TZP 15 mg directly to achieve the best effect of glycemic 
      reduction. However, most of the included studies have the background of basic 
      medication, the independent efficacy and safety of different doses of TZP still 
      need to be tested. SYSTEMATIC REVIEW REGISTRATION: Unique Identifier: 
      CRD42022341966.
CI  - Copyright (c) 2022 Yu, Hu, Yin, Yang, Zhou and Jian.
FAU - Yu, Yunfeng
AU  - Yu Y
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
AD  - The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Hu, Gang
AU  - Hu G
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Yin, Shuang
AU  - Yin S
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Yang, Xinyu
AU  - Yang X
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Zhou, Manli
AU  - Zhou M
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Jian, Weixiong
AU  - Jian W
AD  - College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
LA  - eng
PT  - Systematic Review
DEP - 20220831
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9472131
OTO - NOTNLM
OT  - dose
OT  - meta-analysis
OT  - tirzepatide
OT  - trial sequential analysis
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- 2022/09/20 06:00
MHDA- 2022/09/20 06:01
PMCR- 2022/01/01
CRDT- 2022/09/19 04:32
PHST- 2022/07/09 00:00 [received]
PHST- 2022/08/10 00:00 [accepted]
PHST- 2022/09/19 04:32 [entrez]
PHST- 2022/09/20 06:00 [pubmed]
PHST- 2022/09/20 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.990182 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Aug 31;9:990182. doi: 10.3389/fcvm.2022.990182. 
      eCollection 2022.