if excess fat causes diabetes why do some diabetes drugs cause weight gain?
Okay so first of all, the idea that excess fat itself causes diabetes is kinda half-baked. I'm assuming here you mean type 2 diabetes mellitus and not type 1 or diabetes insipidus. Visceral fat tissue plays a role- it can release inflammatory cytokines to contribute to insulin resistance- but it's not the sole cause of T2DM. There are people with large amounts of fat that don't develop T2DM and people who are lean that do. Aging, physical inactivity, high-sodium diets, and generally hypercaloric diets factor into it, even if adiposity is not considered "excessive," and there are variations or mutations in insulin receptor genes that can also cause resistance.
Let's talk about how our body handles glucose. Basically: our body likes to get some of our energy from glucose because it can be rapidly metabolized into energy, whereas fat and protein take longer. Our body wants to keep our glucose in a set range.
When you eat carbs, your gut breaks it down into glucose, its transported into your blood, and your pancreas releases insulin to help that glucose get into the cells (predominantly muscle) to be used for energy.
The liver can take in glucose without insulin. (Muscles can also take in some glucose without insulin, but this typically happens during exercise).
When muscles become insulin resistant, or when glucose is otherwise high, the liver takes in more glucose, which is turned into fatty acids for storage. Some fatty acids in the liver utlimate decreases insulin signaling.
When your body doesn't have enough dietary sugar, the liver will make it through a process called gluconeogenesis (gluco = glocuse, neo = new, genesis = formation- basically, fancy word for "process that makes new glucose"). One of insulin's roles is to tell the liver, "hey, stop making more glucose! We have enough right now!"
Thus with insulin resistance, you end up needing more insulin to get glucose into cells.
As you need more and more insulin, it gets harder and harder for your pancreas to keep up, and your blood sugar starts to go up, you start losing glucose in your pee, and your liver gets confused and thinks its needs to make more glucose.
But back to the "why do some diabetes drugs cause weight gain."
The treatment of T2DM is primariyl focused on reducing blood glucose levels, as the blood glucose itself can be quite harmful long-term. Diabetes drugs work in several different ways.
Some drugs called SGLT-2 inhibitors, eg empagliflozin or canagliflozin, help reduce blood sugar by helping you pee out more glucose (SGLT-2 is a transporter that reabsorbs glucose from urine back into your blood; if you block it, that sugar is peed out). Potential weight loss: if you pee out calories, they won't become stored as energy. Problem: more sugar in your pee feeds bacteria, can lead to UTIs.
Some drugs called alpha-glucosidase inhibitors, reduce blood sugar by delaying glucose absorption in your gut.
Metformin primarily reduces the amount of new glucose your liver makes.
Many drugs either are insulin, help your body secrete more insulin, or help your body respond better to the insulin you are making. What happens when our body has more insulin or responds better to it? Blood glucose gets into tissues, where it can be stored as fat. Hence, weight gain.
The glitazones (eg, pioglizaone) also can cause weight gain by causing edema or water retention because, while they help your body respond to insulin better, they also increase sodium and water resoprtion in the kidneys.
GLP-1 receptor agonists (eg, Ozempic) mimic GLP-1 a hormone that increases insulin secretion when glucose is high. However, it also makes your stomach empty slower and works in the brain to increase satiety and reduce hunger, so you eat less when you're on them. The reduction in calories consumed drives the weight loss.
TL;DR: Not all diabetes drugs cause weight gain, but some diabetes drugs may because they help your body store blood sugar as energy (eg fat) that would otherwise, eventually, be peed out. One class can also cause water retention.
