Preheat oven to 375°F (190°C) and grease a 9x5 inch loaf pan or line a baking sheet with parchment paper.
Prepare the stuffing by mixing the cooked macaroni with the shredded cheddar cheese until well combined.
In a large mixing bowl, combine ground beef, breadcrumbs, eggs, milk, minced onion, minced garlic, oregano, salt, pepper, and 1/4 cup of the ketchup.
Lay a piece of parchment paper on a flat surface and press the meat mixture into a 10x12 inch rectangle.
Spread the macaroni and cheese mixture over the meat, leaving a 1-inch border at the edges.
Carefully roll the meatloaf into a log starting from the short end, using the parchment paper to assist, and pinch the seams and ends firmly to seal.
Place the loaf seam-side down into the loaf pan or onto the prepared baking sheet.
In a small bowl, whisk together the remaining 3/4 cup ketchup, brown sugar, and yellow mustard to create the glaze.
Brush the glaze evenly over the top and sides of the meatloaf.
Bake for 60 minutes or until the internal temperature reaches 160°F (71°C) on a meat thermometer.
Allow the meatloaf to rest for 10 to 15 minutes before slicing to ensure the cheese center remains intact.