Metformin Alternatives: What to Try When Metformin Isn't Right

Metformin works well for many people, but side effects, kidney limits, or not hitting blood sugar goals happen. If metformin gave you bad stomach problems, didn't lower your A1c enough, or your doctor warned against it, you have real options. Below are clear alternatives, what they do, and who they fit best.

Prescription drug alternatives

GLP-1 receptor agonists (semaglutide, liraglutide): These drugs lower A1c and help you lose weight. They come as injections (weekly or daily), can reduce heart risk in some people, and often cut appetite. Side effects: nausea, occasional vomiting, and cost can be high. Good if weight loss and strong A1c drop are priorities.

SGLT2 inhibitors (empagliflozin, canagliflozin): Pills that help the kidneys remove extra glucose through urine. They lower A1c moderately, help with heart failure and some kidney disease, and often lower blood pressure. Watch for genital infections and reduced effect if kidney function is low. Great choice if you have heart or kidney concerns.

DPP-4 inhibitors (sitagliptin and others): These are gentle, weight-neutral pills with few side effects. They lower A1c modestly and rarely cause hypoglycemia. They’re an option when you need mild control and want something well tolerated.

Sulfonylureas (glipizide, gliclazide): Cheap and effective at lowering blood sugar, but they can cause low blood sugar (hypoglycemia) and weight gain. Use carefully, especially if you’re older or have unpredictable meals.

Thiazolidinediones (pioglitazone): Improve insulin sensitivity and lower A1c well. Downsides include weight gain, fluid retention, and rare bone fracture risk. Avoid if you have heart failure.

Insulin: When pills aren’t enough, insulin gives strong control. It works fast and reliably but requires injections and brings hypoglycemia risk and possible weight gain.

Alpha-glucosidase inhibitors (acarbose): Modest A1c drops and mostly act on after-meal blood sugar. Gas and bloating are common—some people can’t tolerate them.

Non-drug options and practical tips

Diet and weight loss: Losing 5–10% of body weight can cut A1c and sometimes reduce or stop the need for meds. Focus on a moderate calorie deficit, higher protein, and consistent carbs per meal.

Exercise: Aim for regular aerobic and strength training. Muscle helps use glucose better and improves insulin sensitivity.

Bariatric surgery: For people with higher BMI and uncontrolled diabetes, surgery can sharply improve blood sugar and even cause remission. It’s major, but very effective for some.

What to discuss with your doctor: your A1c target, kidney and heart health, risk of low blood sugar, weight goals, side effects you’ll tolerate, and cost/insurance coverage. If metformin caused side effects, mention those specifically—doctors can often switch to a different drug or adjust doses.

One recent study even suggests metformin raises a molecule called lac‑Phe that may reduce appetite, but that doesn’t mean you must stay on metformin if it’s not working for you. The right choice depends on your health, goals, and what you’re willing to manage.

Talk openly with your provider. With so many safe alternatives, you can find a plan that fits your life and your numbers.