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GLP-1 (Glucagon-Like Peptide-1) inhibitors, more accurately known as GLP-1 receptor agonists, are a class of medications primarily used to treat type 2 diabetes and obesity. Here's a comprehensive look at what they are, how they work, their benefits, and considerations: How They Work: Mimicking GLP-1: GLP-1 receptor agonists mimic the function of the GLP-1 hormone, which is naturally released in the gut in response to food intake. They stimulate insulin secretion from the pancreas when blood glucose levels are high, suppress glucagon release (which would normally increase blood glucose), slow gastric emptying, and increase satiety signals to the brain. Mechanisms: Insulin Release: They help the body release insulin more effectively in response to meals. Glucagon Inhibition: They reduce the amount of glucagon, which helps lower blood sugar. Gastric Emptying: By slowing how quickly food leaves the stomach, they control post-meal blood sugar spikes. Appetite Suppression: They signal to the brain to reduce food intake, aiding in weight management. Benefits: Blood Sugar Control: Effective in lowering HbA1c levels, managing blood sugar in type 2 diabetes. Weight Loss: They have been shown to reduce appetite and body weight, making them useful for obesity management. Cardiovascular and Renal Benefits: Some GLP-1 receptor agonists have demonstrated benefits in reducing cardiovascular risks and improving renal outcomes in diabetic patients. Common Medications: Semaglutide (Ozempic for diabetes, Wegovy for weight loss) Liraglutide (Victoza for diabetes, Saxenda for weight loss) Dulaglutide (Trulicity) Exenatide (Byetta, Bydureon) Tirzepatide (Mounjaro, Zepbound) - a dual agonist that also targets GIP receptor. Side Effects: Gastrointestinal Issues: Nausea, vomiting, diarrhea, and constipation are common, especially when starting treatment. Ozempic Face: Rapid weight loss can lead to sagging skin on the face. Other Side Effects: Less common but more serious side effects include pancreatitis or potential thyroid tumors. Considerations: Administration: Most are injectable, though there's an oral semaglutide option. Cost: These medications can be expensive, potentially limiting access. Off-label Use: There's growing off-label use for weight loss, which brings up debates on ethics, safety, and long-term effects. Insurance and Coverage: Coverage can be variable, with some insurance plans not covering these drugs for weight loss unless certain criteria are met. Long-term Effects: While effective, the long-term effects are still under study, especially with the newer drugs and higher doses used for weight loss. Current Developments: Research: There's ongoing research into their use for other conditions like non-alcoholic fatty liver disease and polycystic ovary syndrome. Market Impact: The popularity of these drugs has significantly influenced the pharmaceutical market, with companies like Novo Nordisk and Eli Lilly seeing substantial growth due to these medications. In summary, GLP-1 receptor agonists represent a significant advancement in managing type 2 diabetes and obesity, offering multiple health benefits alongside some considerations regarding side effects, costs, and ethical use.

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Dewberry discusses our work on the Carlisle Road Diet—a complete streets and traffic calming initiative project—in Cumberland County, Pennsylvania. Transcript: The Carlisle Road Diet in Cumberland County, Pennsylvania, was a complete streets and traffic calming initiative, completed in 2011. As a result of our comprehensive traffic study, we made several recommendations for traffic pattern changes that were in line with PennDOT's Smart Transportation Initiative. Two streets were converted from four vehicular lanes to three, with a dedicated bike lane in each direction. The bike lanes also provide easier parallel parking and a safer space to enter and exit parked cars. Additional improvements were accomplished through curb extensions; ADA curb ramps; pedestrian signals enhancements; and major traffic signal upgrades, including the first full implementation of the InSync® adaptive signal system in Pennsylvania. All of these improvements enhance Carlisle's small town feeling; reduce accidents; promote walking and bicycling; maximize downtown business success; improve parking access; and reduce truck traffic in the downtown area.

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