49Background 50 Momordica charantia L. (Cucurbitaceae) has been used to control hyperglycemia in people with 51 type 2 diabetes mellitus in Asia, South America, and Africa for decades. However, a meta-analysis 52 of clinical trials confirmed very low-quality evidence of its efficacy. To potentially increase the 53 certainty of evidence, we evaluated the effect of M. charantia L. in comparison with vehicle on 54 glycemic control in animal models of type 2 diabetes mellitus.
55
Methods
56Review authors searched in MEDLINE, Web of Science, Scopus, and CINAHL databases without 57 language restriction through April 2019. Two authors independently evaluated full texts, assessed 58 the risk of bias, and extracted data. We analyzed the influence of study design and evidence of 59 publication bias.
60
Results
61The review included 66 studies involving 1861 animals. They had a follow up between 7 and 90 62 days. Majority 29 (43.9%) used Wistar albino rats, and 37 (56.1%) used male animals. Thirty-two 63 (48%) used an aqueous extract of fresh fruits. M. charantia L. reduced fasting plasma glucose 64 (FPG) and glycosylated hemoglobin A1c in comparison to vehicle control (42 studies, 815 65 animals; SMD, -6.86 [95% CI; -7.95, -5.77], 3 studies, 59 animals; SMD; -7.76 [95%CI; -12.50, -66 3.01]) respectively. Magnitude of FPG was large in Wistar albino rat subgroup; SMD; -10.29, 67 [95%CI; -12.55, -8.03]. Publication bias changed FPG to non-significant -2.46 SMD, [95%CI; -68 5.10, 0.17]. We downgraded the evidence to moderate quality due to poor methodological quality, 69 high risk of bias, unexplained heterogeneity, suspected publication bias, and lack of standardized 70 dose. 4 71 Conclusion 72 M. charantia L. lowers elevated plasma glucose level in type 2 diabetes mellitus animal models. 73 Publication bias and poor methodological quality call for future researches to focus on 74 standardizing dose with chemical markers and provide measures to improve preclinical type 2 75 diabetes mellitus studies. 76 Systematic review registration CRD42019119181 77 Keywords 78 Bitter gourd; type 2 diabetes mellitus; efficacy; safety; meta-analysis; preclinical. 79 80 81 82 83 84 85 86 87 88 89 90 91 92 5 93 94 Introduction 95 Type 2 diabetes mellitus (T2DM) is a chronic hyperglycemic condition in response to 96 progressively impaired glucose regulation due to insulin resistance and beta-cell dysfunction [1,2]. 97 The chronicity of hyperglycemia causes microvascular complications in the retina, renal 98 glomerulus and peripheral nerves [3]; and increases the risk of accelerated atherosclerosis and 99 premature death [4]. Other complications include dementia, sexual dysfunction, depression and 100 lower-limb amputations [5-7]. 101 People with T2DM use oral hypoglycemic agents (OHAs) for glycemic control and ameliorating 102 diabetes complications, but the OHAs have in recent years been linked to intolerable side effects 103 and increasing failure rate [8], leaving the majority of people with T2DM using medicinal plants 104 as alternative the...