Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes.

BACKGROUND AND AIMS: To assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI). RESULTS: Twenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA1c (MD = -1.72, 95% CI [-2.32; -1.12]), and fasting blood glucose (MD = -1.93, 95% CI [-2.81; -1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events. CONCLUSION: Tirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.

Safety and Efficacy of Teplizumab for Treatment of Type One Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Type one diabetes mellitus (T1DM) is an autoimmune disease characterized by gradual destruction of beta cells in islets of Langerhans. Teplizumab is a humanized anti- CD3 monoclonal antibody, which may have beneficial effects for T1DM patients. OBJECTIVE: The aim of the study was to assess the safety and efficacy of teplizumab in T1DM patients. METHODS: We searched electronic databases using related keywords for randomized clinical trials assessing the safety and efficacy of teplizumab. We evaluated the retrieved citations for eligibility, and we extracted the data and then analyzed it using Review Manager Software. RESULTS: We included eight randomized clinical trials with 866 patients. Teplizumab was associated with lower insulin use than placebo at 6 months (MD = -0.17, 95% CI [-0.24, -0.09], P < 0.001), 12 months (MD = -0.12, 95% CI [-0.18, -0.06], P < 0.001), 18 months (MD = -0.22, 95% CI [-0.32, -0.11], P < 0.001) and 24 months (MD = -0.17, 95% CI [-0.28, -0.06], P = 0.003). The area under the curve of C-peptide was significantly increased in teplizumab group at 12 months (MD = 0.08, 95% CI [0.01, 0.15], P = 0.03), 18 months (MD = 0.13, 95% CI [0.01, 0.25], P = 0.03) and 24 months (MD = 0.13, 95% CI [0.01, 0.24], P = 0.03). No significant effect of teplizumab on HbA1c levels was observed at any time point. Teplizumab was found to be associated with some side effects such as lymphopenia, skin and subcutaneous tissue disorders. CONCLUSION: Teplizumab is associated with lower insulin use and higher AUC of C-peptide in type 1 diabetic patients with no significant effect on Hb1c levels. Besides, teplizumab has shown some adverse effects.

Efficacy of probiotic supplementation in patients with diabetic nephropathy: A systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is one of the diabetes mellitus complications, which develops in approximately one-third of diabetic patients. Probiotics are microorganisms such as Lactobacillus and Bifidobacterium which have some benefits with gastrointestinal disorders and diabetic patients. AIM: We aim to assess the efficacy of probiotic supplementation in patients with diabetic nephropathy (DN). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane on 20 august 2019 and updated the search on 26 April 2020 using relevant keywords. Studies were screened for eligibility. We extracted the data from the relevant articles and then these data were pooled as mean difference (MD) with a 95% confidence interval (CI), using Review Manager software (ver. 3.5). RESULTS: Pooled data from four trials compared probiotics with a placebo showed a significant reduction in insulin (MD = -1.99, 95% CI [-3.99, 0.01]) and Homeostatic Model Assessment for Insulin Resistance (MD = -3.87, 95% CI [-7.51, -0.22]), High-sensitivity C-reactive protein (MD = -1.55, 95% CI [-2.19, -0.92]), malondialdehyde (MD = -0.77, 95% CI [-0.96, -0.58]), sodium (MD = -0.93, 95% CI [-1.87, -0.01]), but the total antioxidant capacity was significantly increased (MD = 62.29, 95% CI [18.34, 106.24]), while no significant effect on other lipid profiles, oxidative stress biomarkers or kidney function parameters like creatinine and glomerular filtration rate. Two trials showed that probiotic soy is better than conventional soy in terms of kidney function and lipid profiles. CONCLUSION: Probiotics supplementation decreases serum insulin and insulin resistance, but it has no beneficial effect regarding kidney function, body-weight, and lipid profiles, with a moderate positive effect regarding some oxidative stress biomarkers. Also, probiotic soy protein may improve kidney function and lipid profiles. Further studies are needed to confirm our findings and to assess the long-term effect.