Metformin alternative: what to try if metformin isn’t working for you

If metformin gives you bad stomach issues, your kidney function is low, or it just isn’t controlling your blood sugar, you have choices. This page explains practical alternatives, when to think about switching, and what each option really does — in plain language you can use before talking to your doctor.

When to consider an alternative

Think about changing if you have persistent GI side effects even on extended‑release metformin, a confirmed eGFR below 45 mL/min/1.73 m2 (and you should stop metformin if eGFR drops under 30), pregnancy plans, or repeated low blood sugar while on other drugs. Also switch if you develop B12 deficiency or aren’t losing weight when weight loss is a goal. Always check labs (kidney function, B12) and discuss risks before making any change.

Common alternatives and what to expect

SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) lower blood sugar by making the kidneys remove excess glucose. Upsides: modest weight loss and heart/kidney protection for many patients. Downsides: higher risk of genital infections and dehydration. Not ideal if you get urinary infections often or are volume‑depleted.

GLP‑1 receptor agonists (semaglutide, liraglutide) mimic gut hormones to lower glucose and reduce appetite. They often help with weight loss and can improve heart outcomes. Expect possible nausea at first; injections are common, though oral semaglutide exists. These are a good pick when weight and cardiovascular risk matter.

DPP‑4 inhibitors (sitagliptin, linagliptin) are pills that modestly lower glucose with few side effects and low hypoglycemia risk. They’re gentle but usually less powerful than SGLT2s or GLP‑1s. Useful when you need a well‑tolerated add‑on.

Sulfonylureas (glipizide, gliclazide) cut blood sugar effectively but carry a higher risk of hypoglycemia and weight gain. They’re inexpensive and still useful when cost is a big factor, but not great if you’re prone to low blood sugar.

Thiazolidinediones (pioglitazone) improve insulin sensitivity and can be effective long term. Watch for weight gain, fluid retention, and rare risks like heart failure worsening.

Insulin remains the most reliable way to lower blood sugar if oral drugs aren’t enough. Modern insulin regimens can be simple and flexible — ask about basal insulin first if your fasting sugars are high.

Smaller options: alpha‑glucosidase inhibitors and meglitinides can be helpful for specific meal‑related spikes. Lifestyle still matters: focused weight loss, carb timing, and consistent activity often reduce the need for stronger meds.

Ready to change treatment? Bring a recent eGFR and A1c to your appointment, list symptoms you hate (nausea, lows, weight gain), and ask your clinician about side effects and costs. A tailored plan beats trial and error — and your doctor can help you pick the safest, most practical metformin alternative.