Despite your best efforts in exercise and nutrition, your care team insists on putting you on another medication. What gives?
It’s not you. It’s diabetes.
Typically, when we think about diabetes, our brains immediately jump to “insulin!” Whether you’re not producing enough, or your body has stopped producing it completely, insulin is a key player.
But what you may not know is that diabetes affects more than just insulin. It is a metabolic disorder of the endocrine system (hormones!).
Let’s talk about the other hormones affected when diabetes is at play and how the medications your care team prescribes can help.
A quick refresher of what diabetes is.
Type 2 diabetes involves the cells of the body not responding appropriately to insulin, which leads to a buildup of glucose in the bloodstream. Type 1 diabetes is an autoimmune disease that leads to the destruction of the beta cells that produce insulin, leading to dependence on exogenous (injected or inhaled) insulin.
While we diagnose and treat them differently at first, diabetes exists on a spectrum. Some people with type 2 diabetes may become insulin dependent at some point, and some people with type 1 diabetes experience metabolic syndrome and insulin resistance. Everyone is unique, so keep that in mind.
We’ll focus on type 2 diabetes in this article as the medications are FDA approved for that diagnosis. However, there is evidence in the literature that points to many of these medications being beneficial for those with other types of diabetes1, 2.
Another important piece to note is that diabetes puts you at risk for developing other hormone-related disorders, which affect your thyroid, adrenals, pituitary, and gonads3. If you develop one or more of these, your endocrinologist will prescribe medications and manage this alongside your diabetes.
So how does your care team decide what to prescribe? Contrary to popular belief, they’re usually not just throwing darts at a pharmacy catalog.
Enter the American Association of Clinical Endocrinologists (AACE) guidelines. These are a collection of algorithms that tell your care team and you which action would be most beneficial for you next4. These decisions are typically based on:
It’s also not uncommon for these guidelines to recommend combination therapy early on. Diabetes doesn’t come from one broken body system. It comes from many systems being dysregulated at once. That’s why your team may prescribe a GLP-1 receptor agonist and metformin and an SGLT-2 inhibitor. They’re each working on different hormonal pathways to restore metabolic balance.
Bottom line: You’re not being “overmedicated.” You’re being strategically supported. Or at least, you should be.
Let’s look at the most commonly prescribed medications, how they work, and why they’re important for your diabetes management.
What it targets: Liver glucose output and insulin resistance.
What do you mean I need medication for my liver? In people with diabetes, the liver misbehaves. It secretes glucagon at inappropriate times, like in the morning when you’re fasting or after meals.
How to take it: Oral tablet.
How it works:
Why it matters: Metformin works on three key issues in type 2 diabetes. It has been tested and used for decades with no serious long-term risks or side effects6. It is extremely cost effective.
Side note: Gastrointestinal side effects are common early. Over time, they typically improve. Consider extended-release formulation and note that probiotics may help some people.
What it targets: GLP-1 receptors.
Glucagon like peptide-1 is an incretin hormone that signals the pancreas to make insulin in response to food. In type 2 diabetes, GLP-1 production or signaling is reduced. These meds mimic or enhance that signal7.
How to take it: Subcutaneous injection. Rybelsus is an oral tablet.
How it works:
Why it matters: GLP-1 receptor agonists address multiple dysregulated systems and have evidence for heart and kidney protection8, 9.
Side note: Nausea is common initially and often improves with slower dose increases and smaller, lower-fat meals. Not for everyone; discuss persistent symptoms with your clinician.
What about tirzepatide (Mounjaro)? Similar to GLP-1 receptor agonists, but adds GIP action. The dual mechanism may enhance effects on weight loss and satiety.
What it targets: Kidneys and glucose reabsorption.
Your kidneys normally reabsorb filtered glucose. SGLT-2 inhibitors block that reabsorption10.
How to take it: Oral tablet.
How it works:
Why it matters: Reduces glucose load without extra insulin. Strong evidence for heart failure and kidney disease benefits11, 12.
Side note: Increased urination and risk of yeast or urinary tract infections. Practical tips to reduce risk include hydration, hygiene, regular bladder emptying, urinating before and after sexual activity, and wearing loose cotton undergarments. See clinical recommendations19.
Figure 1: Clinical recommendations for the prevention of urinary tract infections in patients treated with SGLT-2 inhibitors19
What it targets: The enzyme that breaks down GLP-1 and GIP.
Blocking DPP-4 lets your own GLP-1 and GIP persist longer and work better13.
How to take it: Oral tablet.
How it works:
Why it matters: Less potent than GLP-1 agonists but generally well tolerated and weight neutral. Often paired with metformin when a gentle effect is needed.
Side note: Januvia can be expensive. Coverage may favor GLP-1 receptor agonists due to effectiveness compared with cost.
What it targets: Pancreatic beta cells.
These medications stimulate insulin release regardless of glucose levels14. This carries a risk of hypoglycemia.
How to take it: Oral tablet.
How it works:
Why it matters: Cost effective and effective at lowering glucose. Useful early in diagnosis and in limited-insurance settings.
Side note: Make a hypoglycemia plan with your care team. Over time, there may be beta cell exhaustion concerns15.
What it targets: Muscle and fat tissue insulin resistance.
Thiazolidinediones are insulin sensitizers that help your body respond better to insulin, especially in fat, muscle, and liver16.
How to take it: Oral tablet.
How it works:
Why it matters: Addresses a core driver of type 2 diabetes. Slower onset, but can be very effective.
Side note: Can cause weight gain and fluid retention, so not recommended in heart failure. Bladder cancer concerns have been debated; current data is mixed17.
What it targets: Amylin deficiency and post-meal spikes.
Amylin is secreted with insulin and helps control post-meal glucose by slowing digestion, regulating appetite, and modulating hepatic glucose release18. In type 1 and advanced type 2 diabetes, amylin is deficient.
How to take it: Subcutaneous injection.
How it works:
Why it matters: The only other medication FDA approved for people with type 1 diabetes that helps manage post-meal glucose. Can improve time in range when insulin is already optimized.
Side note: Injected before meals, typically three times daily. Requires mealtime insulin adjustments and prebolus changes when starting. Nausea is common initially and often improves.
Needing medication is not a personal failure. It signals that diabetes is complex and multi-system, and that you deserve support.
Taking multiple medications doesn’t mean you’re doing something wrong. It means your care team is looking at the full picture: blood sugar, heart, kidneys, hormones, insulin resistance, and long-term outcomes.
If something isn’t working, ask for a different medication, dose, or approach. Diabetes care is not one-size-fits-all. It is a process of adjusting and collaborating to support your health and life.
You don’t need to feel ashamed about your pill organizer. You don’t need to “earn” fewer meds. You don’t need to prove your worth by white-knuckling through a multi-organ condition.