Several classes of medication lower A1c, with the most effective options reducing it by 1% to 2% or more depending on your starting level and the drug. The right choice depends on more than just blood sugar control: your weight, kidney health, heart risk, and tolerance for side effects all factor in.
Metformin: The Usual Starting Point
Metformin remains the first medication most people with type 2 diabetes are prescribed. At maximum doses, it lowers A1c by as much as 1.5%. It works by reducing the amount of glucose your liver releases into your bloodstream and by helping your body respond better to insulin. It’s inexpensive, widely available, and carries a low risk of causing dangerously low blood sugar. The most common complaints are digestive: nausea, bloating, and diarrhea, which usually improve after a few weeks or with an extended-release formulation.
For many people, metformin alone is enough to bring A1c into a healthy range. When it isn’t, a second medication is added on top of it rather than replacing it.
GLP-1 Receptor Agonists
This class of injectable (and now oral) medications has become one of the most prescribed options for type 2 diabetes, thanks to strong A1c reductions combined with significant weight loss. These drugs mimic a gut hormone that triggers insulin release after meals, slows digestion, and reduces appetite.
In a large network meta-analysis published in The BMJ, semaglutide lowered A1c by an average of 1.4% compared to placebo, making it the most potent in its class. Dulaglutide reduced A1c by about 1.1%, and liraglutide by roughly 1.0%. Semaglutide is available as both a weekly injection and a daily pill. A real-world study from Croatia found that the oral and injectable forms performed similarly after six months, with A1c dropping 1.4% and 1.1%, respectively, a difference that wasn’t statistically significant.
The most common side effects are nausea, vomiting, and diarrhea, particularly when first starting or increasing the dose. These tend to ease over time. Hypoglycemia risk is slightly higher than with metformin alone but still low compared to older drug classes. The 2025 American Diabetes Association guidelines now recommend GLP-1 receptor agonists not just for blood sugar but for their broader benefits in weight management, kidney protection, and liver health.
Tirzepatide: The Dual-Action Newcomer
Tirzepatide targets two gut hormones at once instead of one, and the clinical results have been striking. In the SURPASS trial program, up to 92% of participants reached an A1c below 7%, the standard target for most adults with diabetes. Even more notable: up to 52% reached an A1c below 5.7%, which is the threshold for people without diabetes.
In head-to-head trials, all three doses of tirzepatide outperformed semaglutide for both A1c reduction and weight loss. It also beat a carefully adjusted dose of long-acting insulin. Tirzepatide is given as a weekly injection, and its side effect profile is similar to GLP-1 drugs: mostly gastrointestinal symptoms that improve over time.
SGLT2 Inhibitors
These medications work through a completely different mechanism. Normally, your kidneys filter glucose out of your blood and then reabsorb most of it back. SGLT2 inhibitors block that reabsorption, so excess glucose leaves your body through urine instead of recirculating into your bloodstream. The A1c reduction is more modest than with GLP-1 drugs or metformin, typically in the range of 0.5% to 0.8%, but these medications carry important benefits beyond blood sugar.
SGLT2 inhibitors have been shown to protect the heart and kidneys, and the 2025 ADA guidelines recommend them for people with diabetes who have kidney disease or heart failure regardless of where their A1c sits. They also promote mild weight loss. Because they don’t directly affect insulin, hypoglycemia risk is very low. The main side effects to be aware of are urinary tract infections and yeast infections, both related to the extra glucose passing through the urinary tract.
DPP-4 Inhibitors
DPP-4 inhibitors are oral pills that work by blocking an enzyme that breaks down the same gut hormones targeted by GLP-1 drugs. The effect is gentler: across a meta-analysis of 98 trials, DPP-4 inhibitors lowered A1c by an average of about 0.77%, with individual drugs ranging from roughly 0.55% to 0.88%. They don’t cause weight gain and carry very low hypoglycemia risk, making them a reasonable option for people who need a modest A1c reduction, can’t tolerate stronger medications, or prefer a simple daily pill without injections.
Sulfonylureas
Sulfonylureas are among the oldest diabetes medications still in use. They stimulate your pancreas to release more insulin, and they’re effective: A1c reductions of 1.5% to 2% are typical. They’re also very inexpensive, which keeps them relevant in many treatment plans.
The tradeoff is a higher risk of hypoglycemia (dangerously low blood sugar), the highest of any common diabetes drug class. They also tend to cause weight gain. For these reasons, newer guidelines generally favor other options when cost isn’t the deciding factor.
Insulin
Insulin is the most powerful tool for lowering A1c. When added to oral medications that aren’t achieving target levels, basal (long-acting) insulin can reduce A1c by 1% to 4% or more. There’s no ceiling on its effectiveness because the dose can be adjusted upward as needed.
Most people start with a single daily injection of long-acting insulin, taken at the same time each day. Your dose is gradually increased based on fasting blood sugar readings, a process called titration that typically happens over weeks to months. The main risks are hypoglycemia and weight gain. Many people with type 2 diabetes eventually need insulin, especially as the disease progresses and the pancreas produces less on its own. Starting insulin isn’t a failure. It reflects the natural course of the condition.
How Medications Are Chosen
The decision isn’t just about which drug drops A1c the most. Current guidelines layer several factors on top of blood sugar control. If you have established heart disease or are at high risk for it, GLP-1 receptor agonists and SGLT2 inhibitors are prioritized because of their proven cardiovascular benefits. If you have chronic kidney disease, SGLT2 inhibitors are recommended for kidney protection, and GLP-1 drugs offer additional benefit. If weight loss is a priority, GLP-1 receptor agonists and tirzepatide offer the most meaningful reductions.
Cost and insurance coverage also play a major role. Metformin and sulfonylureas are available as low-cost generics. GLP-1 drugs and tirzepatide can cost over $1,000 per month without insurance, though coverage has expanded significantly. Many people end up on a combination of two or three medications from different classes, each targeting blood sugar through a different pathway. The goal for most adults is an A1c below 7%, though your target may be slightly higher or lower depending on your age, how long you’ve had diabetes, and your overall health.
Which Medications Carry the Lowest Hypoglycemia Risk
If avoiding low blood sugar episodes is a concern, the safest options are DPP-4 inhibitors, SGLT2 inhibitors, and a class called thiazolidinediones, all of which carry very low hypoglycemia risk. GLP-1 receptor agonists and metformin have a slightly higher but still modest risk. Sulfonylureas carry the highest hypoglycemia risk of any oral diabetes drug, and insulin also requires careful monitoring. For older adults or people who live alone, avoiding medications that can cause sudden low blood sugar is an important safety consideration.