LI Jie,CHEN Xiaofei,XU Zihan,et al.Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: a meta-analysis[J].ZHONGGUO YAOFANG,2023,34(01):102-106.
LI Jie,CHEN Xiaofei,XU Zihan,et al.Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: a meta-analysis[J].ZHONGGUO YAOFANG,2023,34(01):102-106. DOI: 10.6039/j.issn.1001-0408.2023.01.20.
Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy: a meta-analysis
To systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2 diabetes mellitus.
METHODS
2
PubMed, Cochrane Library, Web of Science, Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo (or other oral hypoglycemic agents) in the treatment of type 2 diabetes were included, data were extracted and meta-analysis was analyzed using RevMan 5.4 software.
RESULTS
2
A total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect, compared with control group, glucokinase activators significantly reduced glycosylated hemoglobin (HbA
=0.001] and 2 h postprandial blood glucose [MD=-2.28, 95%CI(-2.68, -1.88),
P
<0.000 01] in diabetic patients. In terms of safety, the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR=1.55, 95%CI(1.20,2.01),
P
=0.000 8]. According to the subgroup analysis of organs activated by glucokinas
e activator, the incidence of hypoglycemia in the pancreas-liver dual activator group [RR=1.44, 95%CI(1.11,1.89),
P
=0.007] and liver-selective activator group [RR=2.26, 95%CI(1.02,5.03),
P
=0.05] was higher than that in the control group, the difference was statistically significant.
CONCLUSIONS
2
Glucokinase activators can effectively reduce HbA
1
c, fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes, but the risk of hypoglycemia remains to be addressed.
关键词
葡萄糖激酶激活剂2型糖尿病Meta分析有效性安全性
Keywords
type 2 diabetes mellitusmeta-analysisefficacysafety
American Diabetes Association. Standards of medical care in diabetes:2022[J]. Diabetes Care,2022,45(Suppl 1):S1-S264.
MANNUCCI E,CANDIDO R,MONACHE L D,et al. Italian guidelines for the treatment of type 2 diabetes[J]. Acta Diabetol,2022,59(5):579-622.
STARK CASAGRANDE S,FRADKIN J E,SAYDAH S H,et al. The prevalence of meeting A1C,blood pressure,and LDL goals among people with diabetes,1988-2010[J]. Diabetes Care,2013,36(8):2271-2279.
GRIMSBY J,SARABU R,CORBETT W L,et al. Allosteric activators of glucokinase:potential role in diabetes therapy[J]. Science,2003,301(5631):370-373.
HAEUSLER R A,CAMASTRA S,ASTIARRAGA B,et al. Decreased expression of hepatic glucokinase in type 2 diabetes[J]. Mol Metab,2015,4(3):222-226.
PERREAULT L,FAERCH K,KEREGE A A,et al. Hepatic glucose sensing is impaired,but can be normalized,in people with impaired fasting glucose[J]. J Clin Endocrinol Metab,2014,99(7):E1154-E1162.
AMIN N B,AGGARWAL N,PALL D,et al. Two dose-ranging studies with PF-04937319,a systemic partial activator of glucokinase,as add-on therapy to metformin in adults with type 2 diabetes[J]. Diabetes Obes Metab,2015,17(8):751-759.
KIYOSUE A,HAYASHI N,KOMORI H,et al. Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus[J]. Diabetes Obes Metab,2013,15(10):923-930.
LIU D Y,DU Y,YAO X T,et al. Safety,tolerability,pharmacokinetics,and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-naïve Chinese patients with type 2 diabetes:a randomised controlled,crossover,single-centre phase 1 trial[J]. eClinicalMedicine,2021,42:101185.
MEININGER G E,SCOTT R,ALBA M,et al. Effects of MK-0941,a novel glucokinase activator,on glycemic control in insulin-treated patients with type 2 diabetes[J]. Diabetes Care,2011,34(12):2560-2566.
MORROW L A,LEONSSON-ZACHRISSON M,ERICSSON H,et al. Safety,pharmacokinetics and pharmacodynamics of multiple-ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus[J]. Diabetes Obes Metab,2012,14(12):1114-1122.
VELLA A,FREEMAN J L R,DUNN I,et al. Targeting hepatic glucokinase to treat diabetes with TTP399,a hepatoselective glucokinase activator[J]. Sci Transl Med,2019,11(475):eaau3441.
WILDING J P,LEONSSON-ZACHRISSON M,WESSMAN C,et al. Dose-ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin[J]. Diabetes Obes Metab,2013,15(8):750-759.
ZHENG S,SHAO F,DING Y,et al. Safety,pharmacokinetics,and pharmacodynamics of globalagliatin,a glucokinase activator,in Chinese patients with type 2 diabetes mellitus:a randomized,phase Ⅰb,28-day ascending dose study[J]. Clin Drug Investig,2020,40(12):1155-1166.
ZHU D L,GAN S L,LIU Y,et al. Dorzagliatin monotherapy in Chinese patients with type 2 diabetes:a dose-ranging,randomised,double-blind,placebo-controlled,phase 2 study[J]. Lancet Diabetes Endocrinol,2018,6(8):627-636.
FILIPSKI K J,PFEFFERKORN J A. A patent review of glucokinase activators and disruptors of the glucokinase:glucokinase regulatory protein interaction:2011-2014[J]. Expert Opin Ther Pat,2014,24(8):875-891.
TOULIS K A,NIRANTHARAKUMAR K,POURZITAKI C,et al. Glucokinase activators for type 2 diabetes:challenges and future developments[J]. Drugs,2020,80(5):467-475.
ZHANG Q,RAMRACHEYA R,LAHMANN C,et al. Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes[J]. Cell Metab,2013,18(6):871-882.
LIU S P,AMMIRATI M J,SONG X,et al. Insights into mechanism of glucokinase activation:observation of multiple distinct protein conformations[J]. J Biol Chem,2012,287(17):13598-13610.
BORZILLERI K A,PFEFFERKORN J A,GUZMAN-PEREZ A,et al. Optimizing glucokinase activator binding kinetics to lower in vivo hypoglycemia risk[J]. Med Chem Commun,2014,5(6):802-807.
ZHU D,LI X,MA J,et al. Dorzagliatin in drug-naïve patients with type 2 diabetes:a randomized,double-blind,placebo-controlled phase 3 trial[J]. Nat Med,2022,28(5):965-973.
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