Synergism of amlodipine and telmisartan or candesartan on blood pressure reduction by using SynergyFinder 3.0 and probability sum test in vivo.

This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.

Metformin versus insulin for gestational diabetes: a systematic review and meta-analysis.

BACKGROUND: Metformin is increasingly used in clinical practice for the treatment of gestational diabetes mellitus. However, its safety and long-term effects on fetuses exposed to metformin in uterus remain controversial. METHODS: We systematically searched PubMed, Embase, and the Cochrane database (last search was updated on 1 May 2019) for randomized controlled trials comparing metformin with insulin. Two reviewers extracted the data and calculated pooled estimates by use of a random-effects model. RESULTS: Twenty-four studies were included. Among these, seventeen RCTs (N = 2828 participants) were included for quantitative analyses and seven studies were included only for qualitative synthesis. Metformin lowered the risk of pregnancy-induced hypertension (p = .03; risk ratio (RR) = 0.64; confidence interval (95%CI) [0.44, 0.95]), large for gestational age babies (p = .04; RR = 0.82; 95% CI [0.68, 0.99]), macrosomia (p = .01; RR = 0.63; 95%CI [0.45, 0.90]), neonatal hypoglycemia (p = .001; RR = 0.72; 95%CI [0.59, 0.88]), and neonatal intensive care unit admission (p = .01; RR = 0.74; 95%CI [0.58, 0.94]). Metformin did not increase premature delivery (p = .11; RR = 1.28; 95%CI [0.95, 1.73]), preeclampsia (p = .45; RR = 0.89; 95%CI [0.65, 1.21]), caesarean delivery (p = .20; RR = 0.94; 95%CI [0.85, 1.04]), small for gestational age babies (p = .95; RR = 0.99; 95%CI [0.69, 1.42]). The long-term results seemed to have no adverse effect, but the information was still limited. CONCLUSIONS: According to our review, metformin may have potential benefits for pregnant women and newborns with no obvious adverse effects. However, even more studies are needed to provide evidence for the future use of metformin.