Several classes of medication can lower A1c, ranging from metformin (which typically reduces it by 1.5 to 2 percentage points) to newer injectable drugs like tirzepatide (averaging about 1.8 points). The right choice depends on your starting A1c, other health conditions, and how your body responds. Here’s how the major options compare.
Metformin
Metformin remains the most widely prescribed first-line medication for type 2 diabetes. It works primarily by reducing the amount of glucose your liver releases into your bloodstream. As a single medication, metformin lowers A1c by roughly 1.5 to 2 percentage points, making it one of the most effective oral options available. It’s inexpensive, well studied over decades, and doesn’t cause low blood sugar on its own.
The most common side effects are gastrointestinal: nausea, diarrhea, and stomach upset, especially in the first few weeks. Starting at a low dose and increasing gradually helps most people adjust. An extended-release version is easier on the stomach for many people.
GLP-1 Receptor Agonists
This class includes semaglutide (Ozempic, Wegovy) and liraglutide (Victoza). These are injectable medications, though semaglutide also comes in an oral form (Rybelsus). They work by mimicking a gut hormone that signals your pancreas to release insulin when blood sugar rises, while also slowing digestion and reducing appetite.
Across clinical trials, semaglutide lowers A1c by an average of 1.1 percentage points, with many patients seeing larger reductions depending on their starting level. Beyond blood sugar, semaglutide reduces body weight by an average of 8.5%, which is a meaningful benefit since excess weight makes diabetes harder to manage. The 2025 ADA Standards of Care now recommend GLP-1 receptor agonists specifically for people with type 2 diabetes who also have chronic kidney disease, heart failure, or fatty liver disease, because these drugs appear to protect the heart and kidneys beyond just lowering blood sugar.
Side effects are mostly gastrointestinal: nausea, vomiting, and diarrhea, particularly when starting or increasing the dose. These usually improve over several weeks.
Tirzepatide: The Dual Agonist
Tirzepatide (Mounjaro) is a newer injectable that activates two gut hormone receptors instead of one. In head-to-head analyses across 17 clinical trials, tirzepatide lowered A1c by an average of 1.8 percentage points and reduced body weight by 10.7%. That makes it the most potent option currently available for both blood sugar control and weight loss.
The side effect profile is similar to GLP-1 drugs, with nausea being the most common complaint early on. Tirzepatide is given as a once-weekly injection.
SGLT2 Inhibitors
SGLT2 inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), work in an unusual way: they cause your kidneys to excrete excess glucose through urine. This mechanism is completely independent of insulin, which means they complement almost any other diabetes medication.
Their A1c-lowering effect is moderate, generally in the range of 0.5 to 0.8 percentage points. But A1c reduction is only part of the story. In four major cardiovascular outcome trials, SGLT2 inhibitors significantly reduced the risk of death from heart disease, hospitalization for heart failure, and progression of kidney disease. These benefits held true even in patients without diabetes, which speaks to how broadly protective these medications are for the heart and kidneys. If you have heart failure or kidney disease alongside diabetes, your doctor may prioritize an SGLT2 inhibitor for these protective effects.
Common side effects include genital yeast infections (due to sugar in the urine) and urinary tract infections. They can also cause dehydration, so staying well hydrated matters.
DPP-4 Inhibitors
DPP-4 inhibitors like sitagliptin (Januvia) and linagliptin (Tradjenta) are oral pills that work by extending the life of natural gut hormones that help regulate blood sugar. They’re the gentlest option in terms of side effects: they rarely cause low blood sugar (about ten times less often than sulfonylureas), don’t cause weight gain, and are well tolerated overall.
The trade-off is potency. As a standalone medication, DPP-4 inhibitors lower A1c by an average of only 0.5 percentage points. Combined with another drug like metformin, that improves to about 1.0 point. They’re a practical choice for older adults or people with kidney disease who need modest blood sugar improvement without the risk of dangerous lows.
Sulfonylureas
Sulfonylureas (glipizide, glimepiride, glyburide) are older, inexpensive oral medications that stimulate your pancreas to release more insulin regardless of your current blood sugar level. They can lower A1c by 1 to 1.5 percentage points, which is substantial.
The downside is that this “always on” insulin stimulation creates a real risk of low blood sugar, especially if you skip meals or exercise more than usual. Among the three commonly prescribed sulfonylureas, glyburide carries the highest risk of severe hypoglycemia (the kind requiring emergency care), while glipizide carries the lowest. At three years of use, roughly 1 in 100 patients on sulfonylureas experiences a severe low blood sugar episode. Sulfonylureas also tend to cause weight gain, which works against long-term diabetes management. Newer drug classes like GLP-1 receptor agonists and SGLT2 inhibitors are considered safer with respect to both hypoglycemia and weight.
Insulin
Insulin is the most powerful tool for lowering A1c because there’s no ceiling on how much blood sugar it can bring down. It’s typically added when A1c remains above 8 to 9% despite oral medications, or used from the start if A1c is above 10 to 12% at diagnosis.
Most people begin with a single daily injection of long-acting (basal) insulin, which provides a steady baseline of blood sugar control throughout the day. If that’s not enough, mealtime (rapid-acting) insulin may be added before meals. The major risks are low blood sugar and weight gain. Insulin requires regular blood sugar monitoring and dose adjustments, so it demands more daily involvement than oral medications.
How These Medications Compare at a Glance
- Strongest A1c reduction: Tirzepatide (1.8%), metformin (1.5 to 2%), insulin (variable, no upper limit)
- Moderate A1c reduction: GLP-1 receptor agonists (1.1%), sulfonylureas (1 to 1.5%)
- Mild A1c reduction: DPP-4 inhibitors (0.5 to 1%), SGLT2 inhibitors (0.5 to 0.8%)
- Weight loss benefit: Tirzepatide, GLP-1 receptor agonists, SGLT2 inhibitors
- Heart and kidney protection: SGLT2 inhibitors, GLP-1 receptor agonists
- Lowest hypoglycemia risk: Metformin, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists
- Highest hypoglycemia risk: Sulfonylureas, insulin
How Long Before You See Results
A1c reflects your average blood sugar over the previous two to three months, so a single test can’t capture changes from a medication you just started. Most doctors recheck A1c about three months after beginning or adjusting a medication. That first follow-up test gives a reliable picture of whether the drug is working. If it’s not producing enough of a drop, your doctor may increase the dose, add a second medication, or switch classes entirely.
Many people with type 2 diabetes eventually take two or three medications together, each targeting blood sugar through a different mechanism. A common combination is metformin plus a GLP-1 receptor agonist or an SGLT2 inhibitor, which addresses blood sugar from multiple angles while also offering weight and cardiovascular benefits.