The medicine you take for diabetes depends on which type you have and what else is going on with your health. For type 2 diabetes, metformin remains the starting point for most people, with newer injectable medications now preferred as the next step when blood sugar stays too high. Type 1 diabetes always requires insulin. The landscape has shifted significantly in recent years, with medications that lower blood sugar while also protecting the heart, kidneys, and helping with weight loss taking center stage.
Metformin: Still the First Step for Type 2
Metformin has been the go-to starting medication for type 2 diabetes for decades, and current guidelines from the American Diabetes Association still place it at the foundation of treatment. It works by reducing how much sugar your liver releases into the bloodstream and helping your cells respond better to insulin. It’s inexpensive, widely available, and doesn’t cause weight gain.
Most people tolerate metformin well, though stomach upset and diarrhea are common early on. Starting at a low dose and increasing gradually, or using the extended-release version, usually helps. When metformin alone isn’t enough to reach your blood sugar goal, the next medication added depends on your specific situation, particularly whether you have heart disease, kidney problems, or need to lose weight.
GLP-1 Medications: The Preferred Next Option
GLP-1 receptor agonists have become the preferred second-line treatment for type 2 diabetes when metformin isn’t enough on its own. These medications mimic a gut hormone that tells your pancreas to release insulin when blood sugar rises, slows digestion, and reduces appetite. The FDA has approved several: exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide, all given as injections (semaglutide also comes in a pill).
The blood sugar lowering power varies across this class. Short-acting versions like exenatide and lixisenatide are taken once or twice daily and work mainly on blood sugar spikes after meals. Long-acting versions like liraglutide (daily), dulaglutide (weekly), and semaglutide (weekly) have a stronger overall effect on blood sugar, particularly fasting levels overnight.
Nausea is the most common side effect, especially in the first few weeks. It typically fades as your body adjusts. Starting at a lower dose and gradually increasing helps most people get through this period.
Tirzepatide: A Dual-Action Newcomer
Tirzepatide activates two gut hormone receptors instead of one, and the results have been striking. In a head-to-head trial published in the New England Journal of Medicine, tirzepatide lowered A1C by 2.01 to 2.30 percentage points depending on dose, compared to 1.86 points for semaglutide. Weight loss was also greater: people on tirzepatide lost an additional 1.9 to 5.5 kg beyond what semaglutide achieved.
The ADA’s 2025 guidelines now list high-potency GLP-1 medications and tirzepatide as the preferred options for people who need more intensive blood sugar control. These are recommended before starting insulin in most cases, because they carry a lower risk of dangerously low blood sugar and offer benefits for weight, heart health, kidneys, and liver.
SGLT2 Inhibitors: Heart and Kidney Protection
SGLT2 inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, work differently from other diabetes drugs. They block the kidneys from reabsorbing sugar, so excess glucose leaves through urine. This lowers blood sugar, but the bigger story is what these medications do beyond glucose control.
In clinical trials and real-world studies, SGLT2 inhibitors reduced the combined risk of cardiovascular death, heart failure hospitalization, and kidney decline by about 30%. Heart failure hospitalizations specifically dropped by 35%. Kidney function decline slowed by roughly 50% in treated patients compared to untreated ones. These benefits hold even in people without diabetes, which is why these drugs are now also prescribed for heart failure and chronic kidney disease on their own.
The main side effects relate to their mechanism: urinary tract infections and genital yeast infections are more common because of the extra sugar in the urine. A rare but serious risk is a type of ketoacidosis where blood sugar may look normal or only mildly elevated, making it easy to miss. This risk is higher in people who are insulin-deficient, severely dehydrated, eating very low-carb diets, recovering from surgery, or fighting an infection. People with a form of slow-onset autoimmune diabetes (sometimes misdiagnosed as type 2) are at particular risk.
Older Oral Medications
Several older pill-based options are still used, though they’ve largely moved to supporting roles as newer medications have proven more effective and safer.
- Sulfonylureas (glipizide, glimepiride) stimulate the pancreas to produce more insulin regardless of blood sugar level. They’re inexpensive and effective, but they cause weight gain and carry a meaningful risk of hypoglycemia, or dangerously low blood sugar.
- DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin) work similarly to GLP-1 medications but in a milder way. A meta-analysis of 14 trials found they achieve nearly the same blood sugar reduction as sulfonylureas, with about 2 kg less weight gain and 76% lower risk of hypoglycemia. They’re well tolerated but less potent than injectable GLP-1 options.
- Thiazolidinediones (pioglitazone) improve insulin sensitivity but can cause fluid retention and weight gain, limiting their use.
Insulin for Type 2 Diabetes
Insulin isn’t just for type 1 diabetes. Many people with type 2 eventually need insulin, particularly when the pancreas can no longer produce enough on its own. Current guidelines recommend trying GLP-1 medications or tirzepatide before adding insulin, but when insulin is needed, several types are available with different timing profiles.
Long-acting insulins like glargine provide a steady baseline over 24 hours with no sharp peak, making them a common starting point. You take one injection daily, usually at bedtime. Intermediate-acting NPH insulin is less expensive but peaks between 4 and 10 hours, which can increase the risk of low blood sugar overnight.
If mealtime blood sugar spikes remain a problem, rapid-acting insulins like lispro or aspart can be added before meals. These start working within 15 to 30 minutes and last 2 to 5 hours. Ultra-rapid formulations kick in within about 5 minutes.
Insulin for Type 1 Diabetes
Type 1 diabetes is an autoimmune condition where the body destroys its own insulin-producing cells. Insulin replacement is the only treatment, and most people use a combination: a long-acting insulin for background coverage and a rapid-acting insulin dosed at every meal based on carbohydrate intake and current blood sugar. Insulin pumps deliver rapid-acting insulin continuously and can be paired with continuous glucose monitors to automate much of the dosing.
A newer development for type 1 is teplizumab, an immune-modulating infusion approved to delay the onset of the disease in people at high risk. In clinical trials, a single 14-day course delayed progression to full type 1 diabetes by a median of nearly three years in at-risk individuals. For children and adolescents already diagnosed, two 12-day infusion courses given 26 weeks apart helped preserve the body’s remaining ability to produce insulin at 78 weeks, though it did not significantly change other clinical outcomes. This treatment targets a very specific population, primarily young people with detectable autoimmune markers but who haven’t yet developed (or have just developed) full diabetes.
How Your Doctor Chooses
The decision tree for diabetes medication has become more personalized. If you have heart disease or heart failure, SGLT2 inhibitors and GLP-1 medications are prioritized for their protective effects. If kidney disease is the main concern, SGLT2 inhibitors offer the strongest evidence. If weight management is a priority, GLP-1 medications and tirzepatide deliver the most significant results. When A1C is more than 1.5 percentage points above your target, guidelines suggest starting with combination therapy or a high-potency agent rather than metformin alone.
Cost plays a real role in these decisions. Metformin and sulfonylureas cost a few dollars per month. GLP-1 medications and SGLT2 inhibitors can run hundreds of dollars, though insurance coverage has expanded. For insulin specifically, Medicare Part D enrollees now pay no more than $35 per month thanks to the Inflation Reduction Act. Lilly caps out-of-pocket insulin costs at $35 for people with commercial insurance or no insurance. Novo Nordisk offers a program where up to three vials or two packs of pens cost $99. About half of U.S. states have also enacted their own insulin copay caps.