Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis

Abstract

ObjectiveTo evaluate the efficacy and safety of dorzagliatin in the treatment of type 2 diabetes mellitus (T2DM) by using meta-analysis and trial sequential analysis (TSA).MethodSearch for clinical trials of dorzagliatin for T2DM in eight databases, with a time limit of build to July 2022. The included studies that met the requirements were carried out for meta-analysis and TSA.ResultsIn terms of efficacy endpoints, meta-analysis showed that dorzagliatin decreased glycated hemoglobin A1c(HbA1c) [mean difference (MD) −0.65%, 95% confidence interval (CI) −0.76 ~ −0.54, P < 0.00001], fasting plasma glucose (FPG) (MD −9.22 mg/dL, 95% CI −9.99 ~ −8.44, P < 0.00001), 2 h postprandial glucose (2h-PPG) (MD −48.70 mg/dL, 95% CI −55.45 ~ −41.96, P < 0.00001), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD −0.07, 95% CI −0.14 ~ −0.01, P = 0.03) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-β) (MD 2.69, 95% CI 1.06 ~ 4.31, P = 0.001) compared with placebo. And TSA revealed that the benefits observed for the current information set were conclusive, except for HOMA2-IR. In comparison with placebo, dorzagliatin increased triglyceride(TG) (MD 0.43 mmol/L, 95% CI 0.30 ~ 0.56, P < 0.00001), total cholesterol (TC) (MD 0.13 mmol/L, 95% CI 0.05 ~ 0.21, P = 0.001), body weight (MD 0.38 kg, 95% CI 0.12–0.63, P = 0.004) and body mass index (BMI) (MD 0.14 kg/m2, 95% CI 0.05–0.24, P = 0.003), while low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were comparable. And TSA demonstrated that TG, TC, body weight, and BMI were conclusive. In terms of safety endpoints, dorzagliatin increased total adverse events (AEs) [risk ratio (RR) 1.56, 95% CI 1.06 ~ 2.30, P = 0.03], while serious AEs, hyperlipidemia, and hypoglycaemia were all comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias.ConclusionDorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and HDL-C. Although dorzagliatin caused a mild increase in TG and TC, it did not increase the incidence of hyperlipidemia, and the small increases in body weight and BMI were not clinically significant enough. In terms of safety, the total AEs caused by dorzagliatin may be a cumulative effect of single AEs, with no drug-related adverse event being reported at a higher incidence than placebo alone. Dorzagliatin's serious AEs, hyperlipidemia, and hypoglycemia are comparable to that of placebo, and dorzagliatin has a good safety profile.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.

New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment

“…A meta-analysis and trial sequential analysis (TSA) incorporating three clinical studies—phase II, phase III (SEED and DAWN trials)—confirmed the benefits of dorzagliatin in lowering HbA1c, FPG, and 2h-PPG. Additionally, TSA affirmed an increase in HOMA2-b and a decrease in HOMA2-IR [ 69 ]. Results from these trials suggest that dorzagliatin can be administered to patients with mild-to-moderate diabetes.…”

“…In terms of safety, despite an overall higher incidence of total AEs in individuals treated with the dual agonist GKA, both the meta-analysis and TSA confirmed that dorzagliatin does not elevate serious AEs. The observed adverse reactions might be attributed to a combination of single AEs and intrinsic individual characteristics, thereby justifying its favorable safety profile [ 69 ]. A notable advantage of dorzagliatin is its safety in controlling hyperglycemia in patients with DKD or renal insufficiency.…”

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