The aim of this systematic review was to evaluate the efficacy and safety of liraglutide versus sitagliptin both in combination with metformin in patients with type 2 diabetes and provide reference basis for rational use of clinical drugs. Several databases were searched, including Web of science, PubMed, Cochrane library, CNKI, and Wanfang database. Only randomized controlled trials (RCTs) of liraglutide versus sitagliptin both in combination with metformin up to 31 August 2016 were included. Data were extracted independently by 2 reviewers, and a fixed or random effects model were used to analyze outcomes that were expressed as odds ratio (OR) or mean difference (MD) and 95% confidence intervals (95% CIs) for different situations. Five RCTs involving 1440 participants were included. Compared with sitagliptin combination with metformin group, participants’ treatment with 1.2 mg and 1.8 mg liraglutide with metformin could significantly lower the level of glycosylated hemoglobin (HbA1c) (P < .00001, MD = −0.35, 95% CI −0.51 to −0.20). Moreover, patients with 1.8 mg liraglutide group had significant body weight loss (P < .00001, MD = −1.12, 95% CI −1.54 to −0.70). However, there were no obvious differences in cutting down the systolic blood pressure and diastolic blood pressure between liraglutide-metformin and sitagliptin-metformin groups. The incidence of gastrointestinal problems was significantly higher than sitagliptin with metformin groups. The results of this meta-analysis indicated that Liraglutide added on to metformin therapy could significantly lower the level of HbA1c and increase body weight loss. Meanwhile, the adverse reactions such as gastrointestinal problems were common in the liraglutide treatment group. Thus, this will provide an important reference for the treatment of patients with type 2 diabetes.

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation‑associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA‑mediated knockdown further aggravated microglia activation‑mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G₀/G₁ phase. The mechanisms of SIRT3 mitigated microglia activation‑induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl‑2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase‑3/9 activity, increased LC3II/LC3I and beclin‑1 protein expression levels, and decreased nucleotide‑binding oligomerization domain, leucine rich repeat and pyrin domain‑containing protein 3 (NLRP3), caspase‑1, IL‑1β and IL‑18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy‑NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease.

Background: Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood. The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice. Methods: Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I ² test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events. Results: Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD −1.31, 95% CI −1.57 to −1.04, P < .00001) for motor UPDRS score, (16 trials; SMD −1.26, 95% CI −1.49 to −1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD −1.02, 95% CI −1.27 to −0.77, P < .00001) for mental UPDRS score, (10 trials; SMD −1.54, 95% CI −1.93 to −1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD −1.56, 95% CI −1.90 to −1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001). Conclusions: P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.