Metformin Alternatives: What Works When Metformin Isn’t Right

Having trouble with metformin side effects, or your doctor wants a different approach? You’re not stuck. There are several drug and non-drug options that can help control blood sugar, each with pros and cons depending on your health, weight goals, and kidney function.

Drug alternatives — quick comparison

Here are common prescription alternatives and what they do in a simple sentence each:

• GLP-1 receptor agonists (liraglutide, semaglutide): Lower blood sugar and often help with weight loss; given by injection or weekly shot.
• SGLT2 inhibitors (empagliflozin, canagliflozin): Help kidneys remove glucose in urine and can protect the heart; watch for dehydration and urinary infections.
• DPP‑4 inhibitors (sitagliptin): Modest blood sugar lowering with low risk of hypoglycemia and good tolerability.
• Sulfonylureas (glipizide, glyburide): Strong glucose lowering but higher risk of low blood sugar and weight gain.
• Thiazolidinediones (TZDs) (pioglitazone): Improve insulin sensitivity; may cause fluid retention and weight gain, so not for heart failure.
• Insulin: The most powerful option to lower blood sugar quickly; used when pills aren’t enough or in advanced cases.
• Alpha-glucosidase inhibitors (acarbose): Slow carbohydrate absorption after meals; they can cause gas and bloating.

Each drug class has different effects on weight, heart, and kidneys. For example, GLP-1s often help with weight loss, while SGLT2s can reduce heart failure risk. Sulfonylureas and insulin carry higher hypoglycemia risk.

Lifestyle, supplements, and practical choices

Don’t underestimate non-drug options. Weight loss, a lower-carb or Mediterranean-style diet, and regular exercise can cut blood sugar significantly and sometimes reduce the need for medication. Bariatric surgery is another option for people with severe obesity and diabetes—many patients see major improvements.

Some people try supplements like berberine, which can have glucose-lowering effects similar to metformin in small studies. Always talk with your clinician before trying supplements, since they can interact with drugs or affect lab tests.

How to choose? Consider your kidney and liver function, heart health, risk of low blood sugar, weight goals, and affordability. If you have kidney disease, some drugs are limited or require dose changes. If weight loss is a priority, GLP-1 drugs are worth discussing.

Not sure which alternative fits you? Bring a list of your meds, recent lab results, and your goals to your next visit. Your clinician can help match the right option and set up safe monitoring. Want help making a note to bring to your doctor? I can help with that.