Subgroup analyses showed that L-carnitine supplementation had a reduction effect on insulin (pmol/l) in trial duration ≥12 week [WMD = −2.33 pmol/l; 95% CI, −4.53 to −0.13; p = 0.038; I2 = 97.9%, p < 0.001], intervention dose ≥2 g/day [WMD = −1.50 pmol/l; 95%CI, −2.53 to −0.47; p = 0.004; I2 = 86.3%, p < 0.001], and participants with obesity (baseline BMI >30 kg/m2) [WMD = −3.39 pmol/l; 95%CI, −6.32 to −0.46; p = 0.023; I2 = 98.2%, p < 0.001]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.