No abstract

Background: Two new classes of drugs approved by USFDA for the treatment of acute migraine are non-peptide Calcitonin Gene-Related Peptide (CGRP) receptor antagonists (rimegepant and ubrogepant) and 5-HT1F receptor agonist lasmiditan. There are no clinical trials comparing these two classes of newer drugs. Aim and Objectives: The present network meta-analysis was conducted with the objective to compare the efficacy of orally administered lasmiditan versus CGRP-receptor antagonists (rimegepant and ubrogepant) in the treatment of acute migraine. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Lasmiditan” AND “Migraine” for articles on lasmiditan; while MeSH terms “Ubrogepant” AND “Migraine;” “Rimegeapnt” AND “Migraine” were used for articles on CGRP-antagonists. Randomized or cross-over studies comparing efficacy of oral lasmiditan and two FDA approved CGRP-antagonists (rimegepant, and ubrogepant) versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidence of 2 h pain-free event was the primary outcome measure while the incidence of 24 h pain-free was the secondary outcome measure compared. Both frequent and Bayesian network meta-analysis were conducted by CRSU MetaInsight software. Results: In 12 eligible studies, seven interventions were compared with total 13795 patients analyzed in the network. Higher treatment ranking for 2 h and 24 h pain-free events was observed for lasmiditan 200 mg and rimegepant 150 mg, respectively. Conclusions: There is strong evidence to conclude that lasmiditan at 200 mg is better drug for immediate (2 h) headache freedom. There is limited evidence to support rimegepant for sustained effect (beyond 24 h).

INTRODUCTIONMetabolic syndrome or insulin resistance syndrome is diagnosed based on the presence of three or more of the following five criteria: central obesity, raised triglycerides(≥150 mg/dl), reduced HDL cholesterol (<40 mg/dl), raised blood pressure (systolic BP≥130 mm Hg or diastolic BP≥85 mm Hg) and raised fasting plasma glucose (FPG≥100 mg/dl) or previously diagnosed type-2 DM.1 Visceral or central obesity is the common and major etiological factor responsible for development of metabolic syndrome. Development of insulin resistance (fasting serum insulin level of >25 mIU/l) is the major initial patho-physiological event responsible for mediating subsequent events and complications of metabolic syndrome.2,3 Hyper-insulinemia induced due to decreased tissue sensitivity to insulin is responsible for sodium retention, sympathetic nervous system stimulation, vascular smooth muscle hypertrophy and oxidative stress.2,3 Hence insulin resistance represents the mechanism or basis for development of hypertension in type-2 DM and vice-versa. Major complication of metabolic syndrome in pre-diabetics is risk of onset of type-2 DM and in existing diabetics the higher incidences ABSTRACT Background: It is unclear and contradictory on to whether carvedilol is preferable over beta-1 blockers as add-on drug in hypertensive pre-diabetic and diabetic patients with metabolic syndrome. The objective of this study was to compare the effects of carvedilol versus beta-1 blockers on hemodynamic parameters, indicators of insulin resistance and plasma lipid levels in hypertensive diabetic and pre-diabetic patients with features of metabolic syndrome. Methods: Electronic database search in Pubmed, Cochrane library and EMBASE was conducted. Randomized or cross-over studies comparing effects of carvedilol against beta-1 blockers were included under analysis. Statistical analysis by inverse variance method and both random and fixed effect models was conducted by using RevMan 5.3. Results: Six studies were eligible and included in the analysis. There was minor but significant decrease in SBP (mean difference, MD = -1.38mm Hg, 95% CI = -2.09,-0.66) and HbA1C% (MD = -0.21%, 95% CI -0.41 to -0.02) by carvedilol in patients with type-2 DM. Conclusions:There is moderate quality of evidence to suggest that carvedilol has mild but significant SBP and HbA1C% lowering effect compared to beta-1 blockers in hypertensive patients with type-2 DM.