Several classes of medication lower blood sugar, each working through a different mechanism. The most commonly prescribed is metformin, which reduces the amount of glucose your liver releases into your bloodstream. Beyond metformin, your options include injectable and oral drugs that boost insulin, block sugar reabsorption in the kidneys, or replace insulin directly. The right choice depends on your type of diabetes, how much blood sugar lowering you need, and whether side effects like weight gain or low blood sugar episodes are a concern.
Metformin: The Usual Starting Point
Metformin is the first medication most people with type 2 diabetes are prescribed. It works in three ways: it reduces the amount of glucose your liver produces, slows glucose absorption from food in your intestines, and helps your muscles and other tissues take up glucose more effectively. In clinical trials, metformin lowered HbA1c (a measure of average blood sugar over two to three months) by about 0.7 to 1.0 percentage points, depending on the dose. That may sound modest, but it’s often enough to bring blood sugar into a healthy range when combined with diet and exercise.
Metformin rarely causes low blood sugar on its own, which is one reason it’s so widely used. It’s also weight-neutral or may cause slight weight loss. The most common side effects are digestive: nausea, diarrhea, and stomach discomfort, which often improve after a few weeks or with an extended-release version of the pill.
GLP-1 Agonists and Dual Agonists
GLP-1 receptor agonists have become some of the most talked-about diabetes medications, partly because they lower blood sugar and promote significant weight loss at the same time. They work by mimicking a gut hormone called GLP-1. When your blood sugar rises after a meal, these drugs stimulate your pancreas to release more insulin, suppress a competing hormone called glucagon that would otherwise raise blood sugar, and slow the rate at which food leaves your stomach so glucose enters your bloodstream more gradually.
The drugs in this class include semaglutide (Ozempic as an injection, Rybelsus as a daily pill), liraglutide (Victoza), dulaglutide (Trulicity), exenatide (Byetta, Bydureon BCise), and lixisenatide (Adlyxin). Most are weekly injections. Among these, semaglutide and tirzepatide tend to produce the greatest reductions in both blood sugar and body weight.
Tirzepatide (Mounjaro) takes the concept a step further. It activates receptors for two gut hormones, GLP-1 and GIP, both of which boost insulin secretion and suppress glucagon. This dual action generally delivers larger blood sugar and weight reductions than GLP-1 drugs alone. The most common side effects for the entire class are nausea, vomiting, and diarrhea, which typically ease over the first few weeks as your body adjusts.
SGLT2 Inhibitors
SGLT2 inhibitors take an entirely different approach. Instead of acting on insulin or the pancreas, they work in the kidneys. Normally, your kidneys filter glucose out of the blood and then reabsorb about 97% of it back into circulation. SGLT2 inhibitors block that reabsorption, causing excess glucose to leave the body through urine. This lowers blood sugar without depending on insulin at all.
Medications in this class include empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). They also promote modest weight loss, though typically less than GLP-1 agonists. Beyond blood sugar control, several of these drugs have proven benefits for heart failure and kidney disease, which is why they’re sometimes prescribed even in people without diabetes. The tradeoff: because extra sugar sits in the urinary tract, these medications increase the risk of urinary tract and yeast infections.
DPP-4 Inhibitors
DPP-4 inhibitors work on the same incretin hormone system as GLP-1 agonists, but more gently. Your body naturally produces GLP-1 after meals, but an enzyme called DPP-4 breaks it down within minutes. DPP-4 inhibitors block that enzyme, letting your own GLP-1 stay active longer. The result is more insulin release when blood sugar is high and less glucagon pushing it higher.
These are oral medications, taken once daily. They include sitagliptin (Januvia, and a newly approved oral solution form called Brynovin), saxagliptin, linagliptin, and alogliptin. They produce a more moderate blood sugar reduction than GLP-1 agonists, but they’re well tolerated, don’t cause weight gain, and carry a very low risk of hypoglycemia. For people who need a mild add-on to metformin and prefer a simple pill, DPP-4 inhibitors fill that role.
Sulfonylureas and Meglitinides
Sulfonylureas are among the oldest diabetes medications still in use. They stimulate the pancreas to release more insulin regardless of whether blood sugar is high or low, which is both their strength and their biggest drawback. They’re effective and inexpensive, but they carry a meaningful risk of hypoglycemia, especially in older adults or people who skip meals. They also tend to cause weight gain. Common examples include glipizide, glyburide, and glimepiride.
Meglitinides (repaglinide, nateglinide) work similarly but act faster and wear off sooner. You take them right before meals to cover the blood sugar spike from eating. Their shorter duration means slightly less hypoglycemia risk than sulfonylureas, but the risk is still higher than with most newer drug classes. Because newer medications offer blood sugar control with fewer side effects, sulfonylureas and meglitinides are used less often as first choices today.
Thiazolidinediones (TZDs)
Thiazolidinediones, primarily pioglitazone, improve insulin sensitivity rather than increasing insulin production. They activate a receptor in fat and muscle cells called PPAR-gamma, which triggers changes in how these tissues store fat and respond to insulin. The downstream effect is that fat tissue absorbs and stores lipids more efficiently, reducing the toxic spillover of fats into the liver and muscles that worsens insulin resistance. Pioglitazone also remodels cell membranes in ways that reduce inflammation, including lowering levels of arachidonic acid, a molecule that drives inflammatory pathways.
TZDs take several weeks to reach their full effect. They don’t cause hypoglycemia on their own, but they can cause fluid retention, which may worsen heart failure in susceptible people. Weight gain is common. These tradeoffs have made TZDs less popular than newer classes, but they remain useful for specific patients, particularly those with significant insulin resistance or fatty liver disease.
Insulin
Insulin is essential for everyone with type 1 diabetes and is used in type 2 diabetes when other medications can’t achieve adequate blood sugar control. Unlike other drugs on this list, insulin directly replaces or supplements what the body can’t produce enough of.
Insulin comes in several forms designed to mimic the body’s natural patterns:
- Rapid-acting (lispro, aspart, glulisine): starts working in 5 to 15 minutes, peaks around 45 to 75 minutes, and lasts 3 to 5 hours. Taken right before meals to cover the blood sugar spike from food.
- Short-acting (regular insulin): starts in 30 to 60 minutes, peaks at 2 to 4 hours, and lasts 6 to 8 hours.
- Intermediate-acting (NPH): starts in about 2 hours, peaks at 4 to 12 hours, and lasts 18 to 26 hours. Often combined with a rapid-acting insulin.
- Long-acting (glargine, detemir, degludec): provides a steady baseline of insulin with no pronounced peak. Glargine lasts about 24 hours. Degludec lasts over 40 hours, allowing more flexible dosing.
Many people with type 2 diabetes start with a single daily injection of long-acting insulin added to their oral medications. Over time, mealtime rapid-acting insulin may be added if needed. The main risk with any insulin is hypoglycemia, particularly with doses that are too high or meals that are skipped. Weight gain is also common. In 2025, the FDA approved two new biosimilar versions of rapid-acting insulin aspart (Merilog and Kirsty), which may help lower costs for people who need mealtime insulin coverage.
How These Medications Compare on Weight
Weight effects vary dramatically across drug classes, and for many people this matters as much as blood sugar control. GLP-1 agonists and dual agonists produce the most weight loss. SGLT2 inhibitors also promote weight loss, though less dramatically. Metformin is roughly weight-neutral or causes slight loss. DPP-4 inhibitors are weight-neutral. On the other side, sulfonylureas, TZDs, and insulin all tend to cause weight gain. If you’re managing both blood sugar and weight, this distinction often shapes which medications make the most sense for your situation.
Hypoglycemia Risk by Drug Class
Not all blood sugar medications carry the same risk of dropping your glucose too low. Sulfonylureas and insulin are the most likely to cause hypoglycemia because they increase insulin levels regardless of what your blood sugar is doing at the time. Meglitinides carry a similar but slightly lower risk. Metformin, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, and TZDs rarely cause low blood sugar on their own because their effects are tied to glucose levels or work through mechanisms that don’t directly flood the body with insulin. However, combining any of these with sulfonylureas or insulin increases the risk.