Metformin alternatives: what works and when
If metformin isn't suitable or doesn't control your blood sugar, you have several real options. Choices depend on your goals: lower A1C, weight control, avoid stomach upset, or improve fertility in PCOS. Here are common alternatives, how they work, and what to expect.
Common medication classes
GLP-1 receptor agonists (liraglutide, semaglutide) are injectable or weekly drugs that lower blood sugar and often cause weight loss. They slow stomach emptying and reduce appetite. Expect nausea at first; they can help when weight loss is a priority. These drugs are strong at lowering A1C but cost more and need prescription and monitoring.
SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) work by removing glucose through the urine. They lower A1C modestly, can reduce weight and blood pressure, and show heart and kidney benefits in many patients. Watch for urinary tract and genital infections and dehydration. Not ideal if you have recurrent infections or low blood pressure.
DPP-4 inhibitors (sitagliptin, saxagliptin) are pills that boost incretin hormones to raise insulin when needed. They are weight neutral and well tolerated with few side effects, but lower A1C less than some other options. Useful when metformin causes stomach problems but strong glucose lowering isn't required.
Sulfonylureas (glipizide, glyburide) stimulate the pancreas to make insulin. They are inexpensive and work quickly but carry a higher risk of low blood sugar and weight gain. They may suit people who need stronger immediate control and have no history of hypoglycemia.
Thiazolidinediones (pioglitazone) improve insulin sensitivity in tissues. They can lower A1C and improve fat distribution, but may cause weight gain, fluid retention, and raise fracture risk. They are sometimes chosen when insulin resistance is central and heart failure is not a concern.
Insulin remains the most powerful option for high blood sugar or when oral drugs fail. Modern basal and meal-time insulin regimens can be tailored to your life, but they require injections and carry hypoglycemia risk.
Pick the right option
Lifestyle and non-drug options matter. Weight loss, low-carb or Mediterranean-style eating, regular strength and cardio exercise, sleep and stress control often reduce medication needs. Bariatric surgery may be considered for people with obesity and uncontrolled diabetes; it can produce major improvements in blood sugar.
Supplements and off-label choices appear online, but evidence varies. Always check with your doctor before trying anything new.
How to choose? Talk with your clinician about your A1C target, weight goals, kidney and heart health, budget, and side effect tolerance. Some drugs suit heart or kidney disease better; others help with weight. Switching or combining medicines should be supervised.
Need help discussing options with your doctor? Bring a list of your priorities—weight loss, pregnancy plans, cost limits, or fear of injections—and ask which alternative best fits them.
Practical tips: start low and go slow, watch blood sugar and weight, report side effects, check kidney function before some drugs, ask about patient assistance programs or generics to lower costs. Keep a glucose log for two weeks after any change so your doctor can see real effects and improvements.
