The main medicines for diabetes are metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, and insulin. For type 2 diabetes, most adults start with metformin and add other medicines as needed. Type 1 diabetes always requires insulin. This guide explains each group in plain language: what it does, how you take it, side effects, and what to ask your doctor.
How Diabetes Medicines Work
Blood sugar rises when your body does not produce enough insulin, cannot use insulin well, or releases too much sugar from the liver. Each medicine group targets one or more of these problems.
- Make insulin work better — metformin, thiazolidinediones
- Get your pancreas to release more insulin — sulfonylureas, meglitinides, DPP-4 inhibitors, GLP-1 agonists
- Remove sugar through the urine — SGLT2 inhibitors
- Replace insulin your body cannot make — injected insulin
- Slow digestion so glucose rises more evenly — GLP-1 agonists, amylin analogs, alpha-glucosidase inhibitors
At-a-Glance Comparison
| Drug Class | Examples | How It Works | A1C Reduction | Main Side Effects |
|---|---|---|---|---|
| Biguanide | Metformin (Glucophage) | Lowers liver glucose, improves insulin sensitivity | 1.0-1.5% | GI upset, rare B12 deficiency |
| GLP-1 agonist | Semaglutide (Ozempic), liraglutide (Victoza), dulaglutide (Trulicity), tirzepatide (Mounjaro) | Boosts insulin release, slows stomach emptying, curbs appetite | 1.0-2.0% | Nausea, rare pancreatitis |
| SGLT2 inhibitor | Empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana) | Removes sugar through urine | 0.5-1.0% | Yeast/UTI, dehydration, rare DKA |
| DPP-4 inhibitor | Sitagliptin (Januvia), linagliptin (Tradjenta) | Extends the body’s own GLP-1 action | 0.5-0.8% | Mild; rare joint pain |
| Sulfonylurea | Glipizide, glimepiride, glyburide | Forces pancreas to release more insulin | 1.0-1.5% | Low blood sugar, weight gain |
| Thiazolidinedione | Pioglitazone (Actos) | Improves insulin sensitivity in muscle and fat | 0.8-1.2% | Fluid retention, weight gain, fracture risk |
| Insulin | Basal (Lantus, Tresiba), mealtime (Humalog, Novolog) | Replaces hormone the body lacks | No upper limit | Low blood sugar, weight gain, injection burden |
Metformin: The Usual Starting Point
Metformin has been used since the 1950s and is the first-line medicine recommended by the American Diabetes Association for most adults with type 2 diabetes. It lowers how much sugar your liver releases and helps muscle cells respond to insulin. It does not cause low blood sugar by itself and is weight-neutral or slightly weight-reducing.
The most common side effect is stomach upset during the first couple of weeks. Taking it with food, starting low, and using the extended-release form usually solves the problem. Metformin is not used if kidney function (eGFR) drops below 30.
GLP-1 Receptor Agonists
GLP-1s mimic a gut hormone that tells the pancreas to release insulin after meals, slows stomach emptying, and reduces appetite. Semaglutide (Ozempic), liraglutide (Victoza), and dulaglutide (Trulicity) are weekly or daily injections; Rybelsus is a daily oral semaglutide. Tirzepatide (Mounjaro) targets both GLP-1 and GIP receptors and has produced the largest A1C and weight reductions of any non-insulin diabetes medicine.
Benefits beyond blood sugar include 8-15 percent weight loss and lower rates of heart attack and stroke in people with cardiovascular disease. Nausea is common when starting, and doses are slowly titrated up.
SGLT2 Inhibitors
SGLT2 inhibitors block the kidney’s sugar reabsorption, so excess glucose leaves in the urine. Empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana) are the common choices. They lower A1C modestly, reduce blood pressure and weight, and have proven benefits for heart failure and chronic kidney disease in landmark trials.
Watch for genital yeast infections and urinary tract infections. Rarely, they can cause diabetic ketoacidosis even when blood sugar looks normal. Stop them before surgery and when sick with vomiting.
DPP-4 Inhibitors
DPP-4 inhibitors such as sitagliptin (Januvia) and linagliptin (Tradjenta) are oral pills that modestly lower A1C with few side effects. They do not cause low blood sugar or weight gain but are generally less potent than GLP-1s or SGLT2s.
Sulfonylureas
Sulfonylureas are older oral medicines that push the pancreas to release more insulin. They are effective and inexpensive but can cause low blood sugar and a few pounds of weight gain. Glipizide and glimepiride are more commonly used than glyburide in older adults.
Thiazolidinediones
Pioglitazone (Actos) improves insulin sensitivity in muscle and fat tissue. It lowers A1C by about 1 percent but can cause fluid retention, weight gain, and increased fracture risk. It is useful in people with fatty liver disease.
Insulin
Insulin is always required for type 1 diabetes and is sometimes necessary in type 2 diabetes, especially during illness, after surgery, or when oral medicines no longer keep A1C at target. Basal insulins (Lantus, Basaglar, Toujeo, Levemir, Tresiba) cover background needs; rapid-acting insulins (Humalog, Novolog, Fiasp, Lyumjev) cover meals.
Our treatment overview and guide to diabetes medications go deeper into dosing regimens and device options.
Choosing the Right Medicine
Your doctor will weigh several factors:
- Starting A1C. Higher A1Cs often need two medications from day one.
- Heart, kidney, or liver disease. GLP-1s and SGLT2s have proven benefits.
- Weight goals. GLP-1s and SGLT2s promote weight loss; sulfonylureas, insulin, and pioglitazone may cause weight gain.
- Hypoglycemia risk. Metformin, GLP-1s, SGLT2s, DPP-4s, and pioglitazone rarely cause lows alone.
- Cost and insurance. Metformin and some sulfonylureas are inexpensive generics; newer injectables are costly.
- Preferences. Oral pills vs. weekly injections matter for adherence.
Cost and Access
Metformin, sulfonylureas, and pioglitazone are available as inexpensive generics. GLP-1s and SGLT2s are brand-name only in most cases and can cost $500-$1,200 per month retail, though commercial insurance and manufacturer savings cards often bring monthly out-of-pocket costs to under $50. Medicare covers these medicines under Part D drug plans. The federal insulin price cap limits insulin out-of-pocket to $35 per month for Medicare beneficiaries as of 2023.
What About Prediabetes?
Metformin is sometimes prescribed off-label for prediabetes, particularly in adults under 60, people with obesity, and women with a history of gestational diabetes. Lifestyle change remains the first-line tool. Read more in our metformin for prediabetes and medication for prediabetes guides.
Questions to Ask Your Doctor
- Which medicine does my heart, kidney, and weight situation favor?
- What A1C reduction should I expect?
- What are the side effects and how will we manage them?
- Will this cause low blood sugar?
- What is my out-of-pocket cost, and is there a generic or savings program?
- When will we recheck A1C to see if it is working?
The Bottom Line
Medicines for diabetes have expanded from a handful of pills to a full toolbox, each targeting a different part of the blood sugar puzzle. Metformin remains the default starting point for type 2 diabetes, with GLP-1s and SGLT2s increasingly added for their heart, kidney, and weight benefits. Insulin is essential for type 1 and sometimes necessary in type 2. Pair any medicine with consistent lifestyle habits, and review your regimen with your doctor every few months to keep it aligned with your goals.
