Alternatives to Metformin: Practical Options and What to Expect

Metformin is the usual first choice for type 2 diabetes, but it isn’t right for everyone. Some people get bad stomach upset, others have kidney or liver issues, and pregnancy rules out metformin for some plans. If metformin doesn’t suit you, there are solid alternatives—some are pills, some are injections, and lifestyle changes often play a big role.

Main drug alternatives

SGLT2 inhibitors (canagliflozin, empagliflozin, dapagliflozin). These pills lower blood sugar and often help with weight and heart or kidney protection. Downsides: higher risk of genital/urinary infections and, rarely, ketoacidosis. They can need dose changes when kidney function is low.

GLP-1 receptor agonists (semaglutide, liraglutide). These injectable drugs lower glucose well and usually cause weight loss. Good if you want weight reduction and heart benefits, but common downsides are nausea and the need for injections. Some newer options come as weekly shots.

DPP-4 inhibitors (sitagliptin, linagliptin). These are oral, generally well tolerated, and weight neutral. They tend to lower A1c modestly, so they’re often paired with other drugs.

Sulfonylureas (glipizide, glyburide). Cheap and effective at lowering blood sugar, but they can cause low blood sugar (hypoglycemia) and weight gain. Use cautiously in older adults or if you have irregular meals.

Thiazolidinediones (pioglitazone). These lower A1c reliably and last a long time, but they can cause fluid retention, weight gain, and are not ideal if you have heart failure.

Alpha-glucosidase inhibitors (acarbose). These reduce post-meal spikes and are taken with food. The trade-off is frequent gas and bloating, which limits their use.

Insulin. If blood sugar is high or other drugs aren’t enough, insulin works quickly and powerfully. Main downside: injection and risk of hypoglycemia. Modern regimens can be simple (once-daily basal insulin) or more complex.

Other options. Colesevelam and bromocriptine can lower glucose in some people but have modest effects and specific side effects. They’re not first-line but may fit niche situations.

How to pick the right option

Start by identifying why metformin isn’t suitable: stomach intolerance, kidney limits, pregnancy, or other reasons. Match the alternative to your goals—want weight loss? Consider GLP-1 or SGLT2. Worried about low blood sugar? Avoid sulfonylureas. Have heart or kidney disease? SGLT2s and some GLP-1s offer benefits beyond glucose control.

Practical tips: check your kidney and liver tests before switching, ask about dose adjustments, and review costs and insurance coverage. Combination therapy is common—many people use two drugs to hit targets safely. Always talk options through with your doctor or pharmacist so you get a plan that fits your health, budget, and daily life.

If you notice severe symptoms like fainting, very fast breathing, or confusion after a medicine change, seek medical help right away. Otherwise, schedule a follow-up to track A1c, side effects, and any needed dose changes.