Diabetes Medications and Side Effects: What to Expect

Managing diabetes isn’t just about checking blood sugar-it’s about understanding what’s in your medicine cabinet and how your body reacts to it. Whether you’re just starting treatment or have been on meds for years, side effects can sneak up on you. Some are mild, like an upset stomach. Others, like low blood sugar or infections, can be serious. The good news? You’re not alone, and there are real ways to handle them.

Metformin: The First-Line Drug with Common but Manageable Side Effects

Most people with type 2 diabetes start with metformin. It’s cheap, effective, and doesn’t cause weight gain or low blood sugar like older drugs. But about 1 in 3 people get stomach trouble-nausea, diarrhea, bloating. It’s not dangerous, but it’s annoying enough that nearly half of new users quit within the first month.

The trick? Start low. Take 500 mg once a day with dinner, not on an empty stomach. After a week or two, bump it up slowly. Switching to the extended-release version cuts GI side effects by about half. If you’ve been on metformin for five years or more, ask your doctor to check your vitamin B12 levels. Long-term use can cause a deficiency, leading to fatigue, tingling in hands or feet, or even memory issues. A simple B12 shot every month fixes it in most cases.

Sulfonylureas: Effective but Risky for Low Blood Sugar

Drugs like glyburide and glipizide force your pancreas to pump out more insulin. They work fast and are cheap. But they’re also the most likely to cause hypoglycemia. About 1 in 6 users have at least one low-blood-sugar episode each year. Some people pass out. Others feel shaky, sweaty, confused-like they’re about to faint.

Why it happens: Skipping meals, drinking alcohol, or over-exercising makes it worse. The 15-15 rule helps: eat 15 grams of fast-acting sugar (glucose tablets, juice, candy), wait 15 minutes, check your blood sugar again. Repeat if needed. If you’re on these meds, always carry glucose. And talk to your doctor if you’re having lows often. There are safer options now.

SGLT2 Inhibitors: Weight Loss and Infections

Drugs like empagliflozin (Jardiance), canagliflozin (Invokana), and dapagliflozin (Farxiga) make your kidneys flush out extra sugar through urine. That lowers blood sugar and helps you lose weight-on average, 4 to 8 pounds in the first few months. Many people love that. But there’s a trade-off.

Up to 15% of women and 5% of men get genital yeast infections. It’s not an STI-it’s just sugar in the urine feeding fungus. Keep the area clean and dry. Wear cotton underwear. Avoid douches. If you get one infection, you’re more likely to get another. Urinary tract infections are also more common. And in rare cases (about 1 in 300), you can develop diabetic ketoacidosis-even if your blood sugar isn’t high. Watch for nausea, vomiting, belly pain, or unusual fatigue. Go to the ER if you feel this way.

GLP-1 Receptor Agonists: Powerful but Hard on the Stomach

These injectables-like liraglutide (Victoza), semaglutide (Ozempic, Wegovy), and the newer tirzepatide (Mounjaro)-are game-changers. They help your body make insulin when it’s needed, slow digestion, reduce appetite, and lower heart risks. Many users lose 10% or more of their body weight. But up to half of people get nausea. About 1 in 5 throw up. Diarrhea is common too.

It’s not fun. But it usually gets better after a few weeks. Start with the lowest dose. Don’t rush the increase. Eat smaller meals. Avoid greasy or spicy foods. If nausea lasts more than a month, talk to your doctor. There are oral versions coming soon, and tirzepatide causes less nausea than semaglutide. If you’re overweight and have heart disease or kidney disease, these are often the best choice-despite the side effects.

Person changing out of wet clothes as yeast fungus fades, SGLT2 inhibitor pill nearby.

Insulin: The Most Effective, But With Real Risks

Insulin is the only option for type 1 diabetes. Many with type 2 need it eventually. It’s powerful. But it’s also the most likely to cause hypoglycemia. People on intensive insulin therapy can have 15 to 30 low-blood-sugar events a year. Fear of lows is why some people skip doses-even when their sugar is high.

Weight gain is another issue. Most gain 2 to 5 kg, which makes blood sugar harder to control. The key? Match your insulin to your food. Don’t inject before a meal you’re not going to eat. Use a continuous glucose monitor (CGM). Studies show CGMs cut severe lows by 40%. Talk to your care team about basal-bolus dosing or insulin pumps. They give more control and fewer surprises.

Thiazolidinediones: Rarely Used, But Still in Play

Pioglitazone (Actos) helps your body use insulin better. But it’s not popular anymore. Why? It causes fluid retention-your legs swell. It can worsen heart failure. It also leads to weight gain and increases bone fracture risk in women. The FDA warned about bladder cancer risk years ago, and while the link isn’t proven, many doctors avoid it. It’s still used in rare cases where other drugs don’t work, but only after careful review.

How to Decide What’s Right for You

There’s no one-size-fits-all. Your doctor should consider:

Do you have heart disease, kidney disease, or obesity?
Are you worried about weight gain or low blood sugar?
Can you afford the drug? Metformin costs $4 a month. GLP-1 drugs can cost $900 without insurance.
Can you handle injections or daily pills?
Do you have other conditions like liver or kidney problems?

For most people, metformin comes first. If you need more, newer drugs like SGLT2 inhibitors or GLP-1 agonists are now recommended before sulfonylureas or insulin-especially if you have heart or kidney disease. The goal isn’t just to lower A1c. It’s to live longer, feel better, and avoid dialysis, amputations, or heart attacks.

Person checking glucose monitor as low blood sugar and weight gain shadows recede.

Real Stories, Real Challenges

One woman in Manchester told me she stopped metformin because she couldn’t handle the diarrhea. She switched to a GLP-1 agonist and lost 12 pounds-but threw up for the first three weeks. She stuck with it. Now her A1c is 5.8%. Another man on insulin had two scary lows at work. He got a CGM. He stopped having them. A third person on SGLT2 inhibitors got a yeast infection every month. She started wearing only cotton underwear and changed out of wet clothes right after workouts. No more infections.

These aren’t rare. They’re normal. The key is talking about them-before you quit your meds.

What to Do If Side Effects Hit

Don’t stop cold turkey. Talk to your doctor first.
Keep a side effect journal: What happened? When? How bad? Did anything help?
Ask about alternatives. There’s always another option.
If you’re worried about cost, ask about patient assistance programs. Many drug makers offer free or low-cost meds if you qualify.
Use a CGM if you’re on insulin or sulfonylureas. It’s the best way to avoid lows.

Side effects aren’t a sign you’re failing. They’re a sign your treatment needs adjusting. The right drug for you isn’t the one with the fewest side effects-it’s the one that keeps you alive, healthy, and able to live your life.

Can diabetes medications cause weight gain?

Yes, some can. Insulin and sulfonylureas often lead to weight gain-usually 2 to 5 kg. Thiazolidinediones like pioglitazone also cause weight gain. But newer drugs like SGLT2 inhibitors and GLP-1 agonists often cause weight loss. Metformin is weight-neutral. If weight is a concern, talk to your doctor about choosing a medication that helps you lose or maintain weight.

What’s the safest diabetes medication?

Metformin is considered the safest first-line drug for type 2 diabetes. It doesn’t cause low blood sugar or weight gain, and it has a long safety record. It’s also the cheapest. But safety depends on your health. If you have kidney disease, metformin isn’t safe. If you have heart failure, SGLT2 inhibitors might be safer. There’s no single safest drug-only the safest one for you.

Do diabetes medications cause kidney damage?

Most don’t. In fact, some protect your kidneys. SGLT2 inhibitors like Jardiance and Farxiga have been shown to slow kidney disease progression, even in people without diabetes. Metformin is safe as long as your kidney function is above 30 mL/min. But some drugs, like sulfonylureas, need dose adjustments in kidney disease. Always get your kidney function checked before starting any new diabetes med.

Can I stop taking my diabetes meds if I lose weight?

Some people can-especially if they lose a lot of weight through diet, exercise, or GLP-1 agonists. Studies show up to 40% of people with type 2 diabetes who lose 10% or more of their body weight can go into remission and stop meds. But you still need regular blood sugar checks. Stopping meds without medical supervision can be dangerous. Never stop on your own. Talk to your doctor about a safe plan.

Why do some diabetes drugs cause yeast infections?

SGLT2 inhibitors make your body pee out extra sugar. That sugar ends up in your urine and around your genitals, creating a perfect environment for yeast to grow. It’s not contagious-it’s a side effect of the drug. Keeping the area clean and dry, wearing cotton underwear, and avoiding tight clothes helps. If you get infections often, your doctor might switch you to a different drug.

Are there any diabetes medications that are safe during pregnancy?

Insulin is the standard during pregnancy because it doesn’t cross the placenta. Metformin is sometimes used off-label and is considered relatively safe (FDA Category B). Most other oral diabetes drugs, including sulfonylureas and SGLT2 inhibitors, are not recommended during pregnancy due to potential risks to the baby. Always talk to your OB and endocrinologist if you’re pregnant or planning to be.

Next Steps: What to Do Today

If you’re on metformin and have stomach issues, ask about switching to the extended-release version.
If you’ve had a low blood sugar episode, get a CGM or talk to your doctor about adjusting your dose.
If you’re on an SGLT2 inhibitor and keep getting yeast infections, try changing your underwear and hygiene habits.
If cost is a problem, ask your pharmacy about generic options or patient assistance programs.
Keep a log of side effects. Bring it to your next appointment.

Diabetes meds aren’t magic pills. They’re tools. And like any tool, they work best when you understand how they work-and how they affect you.