Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant. An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively. Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I² = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I² = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I² = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I² = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one. Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia. The registration number is CRD42022335233. www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).

Background: Suzetrigine, a novel nonopioid analgesic, selectively inhibits voltage-gated sodium channel 1.8 (NaV1.8) and has recently been approved for the management of moderate to severe acute pain. This meta-analysis aimed to evaluate the efficacy and safety of suzetrigine by cumulating data from available evidence. Methods: A literature search was conducted using ClinicalTrials.gov, PubMed, and Cochrane Central Register of Controlled Trials. Five randomized controlled trials (RCTs) were included in the systematic review, with four RCTs in the meta-analysis. The primary efficacy outcomes were time-weighted sum of pain intensity difference over 48 h (SPID 48) and 24 h (SPID 24) between suzetrigine and placebo. Secondary outcomes included proportion of participants achieving ≥30%, ≥50%, and ≥70% reduction in numeric pain rating scale (NPRS) scores at 48 h and safety analysis. Results: Suzetrigine showed significantly better efficacy versus placebo in reducing pain, with a standard mean difference of 5.55 (95% CI 2.97-8.13, P < 0.00001) for SPID 48 and 5.33 (95% CI 2.50-8.16, P < 0.00001) for SPID 24. Odds of achieving ≥30%, ≥50%, and ≥70% reduction in NPRS scores at 48 h were significantly higher in the suzetrigine group (OR 1.95, 1.74, and 1.81, respectively; all P < 0.00001). Suzetrigine showed comparable efficacy to hydrocodone bitartrate-acetaminophen (HB/APAP) with a better safety profile, showing lower incidence of adverse events and gastrointestinal side effects. Conclusion: Suzetrigine appears to be an effective, well-tolerated option for acute pain management, showing superiority to placebo and comparable efficacy to HB/APAP, with a better safety profile. However, future long-term studies are needed to assess its efficacy and safety in various acute pain settings.

Remimazolam is a newer drug in the field of anaesthesia. It combines the properties of midazolam and remifentanil. As the name indicates, midazolam is the parent compound of remimazolam which incorporates the pharmacokinetic properties of remifentanil. Remimazolam is an ultra short acting anaesthetic agent/sedative which rapidly shows its effect after injection and also wears off expeditiously after cessation. Therefore, remimazolam's dosage can be ideally controlled. Since it acts on benzodiazepine receptors, availability of specific antagonist (flumazenil) further adds to its safety in case of overdose.