Does Metformin Cause Hypoglycemia? 6 Diabetes Medications With a Low Hypoglycemia Risk
Key takeaways:
Some Type 2 diabetes medications have a lower risk of hypoglycemia (low blood glucose) than other options. Examples include metformin, Ozempic (semaglutide), and Jardiance (empagliflozin).
These medications work differently from insulin or sulfonylureas, which are more likely to cause hypoglycemia. A few ways they may work include improving insulin sensitivity, reducing glucose production, or removing excess glucose.
Choosing the right diabetes medication involves considering various factors. These include hypoglycemia risk, your health history, and treatment goals. For example, medications with a lower hypoglycemia risk may be preferred for older adults and people with kidney disease.
Table of contents
Managing your blood glucose (sugar) levels is an important part of living with Type 2 diabetes. But it presents some challenges. One of the most pressing concerns is hypoglycemia — when your blood glucose drops too low. This can happen as a side effect of medications used to treat diabetes. If left untreated, hypoglycemia can be life-threatening.
Diabetes medications can have different degrees of hypoglycemia risk. Insulin and sulfonylureas are the most likely to cause true hypoglycemia. Metformin is a common treatment option that your prescriber may recommend. But does metformin cause hypoglycemia? And what about other medications you may be prescribed?
Below, we cover six diabetes medications with a low risk of hypoglycemia.
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Which diabetes medications have a low hypoglycemia risk?
Diabetes medications work in several ways to lower blood glucose levels. How they affect insulin levels — a key hormone that moves glucose out of the blood and into cells — can influence the likelihood of hypoglycemia. This is because insulin directly lowers the amount of glucose in your blood.
Medications with a low hypoglycemia risk don’t directly affect insulin levels, or they primarily trigger insulin release after you’ve eaten. This reduces the likelihood of your blood glucose dropping too low when you’re fasting or between meals. These medications may be preferred for people at a higher risk of hypoglycemia, such as older adults and people with kidney disease.
Hypoglycemia isn’t common when these medications are taken on their own. But this risk goes up if you combine them with other diabetes medications, such as insulin.
1. Metformin
Metformin is a first-choice oral medication for Type 2 diabetes. It works by decreasing the amount of glucose your body makes and absorbs. It also makes your body more sensitive to insulin. Together, these effects help lower blood glucose levels.
Metformin doesn’t cause insulin release. Instead, it helps the existing insulin in your body work better. Because of this, the risk of hypoglycemia tends to be low with metformin.
2. GLP-1 receptor agonists like Ozempic
Ozempic (semaglutide) belongs to the glucagon-like peptide-1 (GLP-1) receptor agonists class. These medications work by simulating the effects of GLP-1, a gut hormone that’s released after you eat. Other examples include:
Victoza (liraglutide)
Trulicity (dulaglutide)
Byetta and Bydureon BCise (exenatide)
Rybelsus (semaglutide)
Real stories: Three people describe what it’s like to take metformin, from side effects to potential benefits.
Treating hypoglycemia: Hypoglycemia is when your blood glucose (sugar) levels drop too low. Experts cover how to recognize and treat hypoglycemia quickly.
Low vs. high blood glucose: Here are the key differences between hypoglycemia and hyperglycemia, from symptoms to how they’re treated.
Ozempic and other GLP-1 receptor agonists do stimulate insulin release. But they primarily have this effect when glucose is present, such as after you eat, which makes hypoglycemia unlikely. They also decrease how much glucose the liver makes, slow the passage of food out of the stomach (gastric emptying), and work on the appetite center of the brain.
3. GIP/GLP-1 receptor agonists like Mounjaro
Mounjaro (tirzepatide) works in a similar but slightly different way compared with GLP-1 receptor agonists. It simulates the effects of two gut hormones: GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). It’s the only GIP/GLP-1 receptor agonist for Type 2 diabetes.
Like Ozempic, Mounjaro stimulates insulin release after you eat. It also has many of the same effects on glucose production in the liver, gastric emptying, and your appetite. Because of this, Mounjaro also has a low risk of hypoglycemia.
4. DPP-4 inhibitors like Januvia
Dipeptidyl peptidase-4 (DPP-4) inhibitors work on the same gut hormones as Ozempic and Mounjaro. But instead of simulating their effects, DPP-4 inhibitors prevent your body’s natural GIP and GLP-1 from being broken down. This causes them to remain active for longer. Examples of DPP-4 inhibitors include:
In general, medications like Ozempic and Mounjaro have a greater effect on blood glucose levels than DPP-4 inhibitors. But they all have a low risk of hypoglycemia.
5. SGLT2 inhibitors like Jardiance
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications that don’t directly affect insulin levels at all. Instead, they cause your kidneys to remove excess glucose through your urine. Because of this, hypoglycemia isn’t likely when SGLT2 inhibitors are taken on their own. Examples of SGLT2 inhibitors include:
6. TZDs like pioglitazone
Thiazolidinediones (TZDs, or glitazones) also don’t affect insulin levels. They work by increasing insulin sensitivity and reducing how much glucose your liver makes. Of the TZDs, Actos (pioglitazone) is prescribed most often.
When TZDs are taken on their own, the risk of hypoglycemia is low. But TZDs are typically taken with other diabetes medications, such as insulin or sulfonylureas, which can increase this risk.
Which diabetes medications have a high hypoglycemia risk?
Some diabetes medications increase insulin levels whether glucose is present or not. This can drive blood glucose levels down even when they’re already low, particularly during periods of fasting or between meals. But with regular monitoring, proper meal and dose timing, and a few simple precautions, you can effectively manage this risk.
There are three types of diabetes medications that fall into this category:
Insulin
Sulfonylureas, such as glipizide, glyburide (Glynase), and glimepiride (Amaryl)
Meglitinides, such a repaglinide and nateglinide
Hypoglycemia risk can also vary across medications within these classes. There are some differences between sulfonylureas, which work by stimulating insulin release. For example, shorter-acting sulfonylureas like glipizide typically have a lower risk of severe hypoglycemia. Longer-acting sulfonylureas, such as glyburide, have a higher risk.
Meglitinides work in a similar way as sulfonylureas. But they start working faster, with effects lasting for a shorter period of time. Because their effects don’t last as long, severe hypoglycemia may be less likely.
How to lower your hypoglycemia risk while taking diabetes medications
The best diabetes medication for you can depend on your hypoglycemia risk, your health history, and other factors. But keep in mind that hypoglycemia is a possibility with any diabetes medication. Here are a few steps you can take to help lower your risk.
Take your medication at the right time. Some diabetes medications can be taken anytime of day. Others, such as sulfonylureas, meglitinides, and fast-acting insulin, need to be timed around meals. This helps match increased insulin levels with the rise in blood glucose that happens after eating.
Check your dose. Injecting too much insulin is a common cause of hypoglycemia. Check to make sure that you’ve selected or drawn up your correct dose. This is also the case for other injections, such as GLP-1 receptor agonists.
Monitor your glucose levels. This can help you detect drops in glucose levels before they become severe. If they’re trending low on your continuous glucose monitor, you should confirm the reading with a fingerstick. Then you can take immediate action by eating a carbohydrate-rich snack if appropriate. Fingerstick blood glucose levels are the most reliable in the setting of hypoglycemia. Your glucose readings can also tell your prescriber if your medications or doses need to be adjusted.
Fuel up properly before workouts. Exercise has many benefits, but it can also cause your blood glucose to drop too low. That’s why it’s a good idea to fuel up properly before your workout, replenish afterward, and keep snacks on hand just in case.
Limit your alcohol intake. Alcohol can increase your risk of hypoglycemia. So it’s a good idea to limit how much you drink. Alcohol can also be risky with metformin, since it can increase the risk of a rare but serious side effect called lactic acidosis. Your diabetes care team can give you guidance on how much may be OK for you to drink.
Even with these steps, hypoglycemia may still happen. Your diabetes care team can help you understand how to recognize and treat hypoglycemia quickly.
The bottom line
Hypoglycemia (low blood glucose) is possible with diabetes medications. But the risk isn’t the same across all medications. Metformin, Ozempic (semaglutide), and Jardiance (empagliflozin) are examples of medications with a low hypoglycemia risk. Insulin, sulfonylureas, and meglitinides have a high risk for hypoglycemia.
Your prescriber will consider your hypoglycemia risk, health history, and other factors when recommending the right diabetes treatment plan for you.
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References
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Douros, A., et al. (2017). Pharmacologic differences of sulfonylureas and the risk of adverse cardiovascular and hypoglycemic events. Diabetes Care.
Gilbert, M. P., et al. (2020). GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: Review of head-to-head clinical trials. Frontiers in Endocrinology.
Gomez-Peralta, F., et al. (2017). Practical approach to initiating SGLT2 inhibitors in type 2 diabetes. Diabetes Therapy.
Meloni, A. R., et al. (2013). GLP-1 receptor activated insulin secretion from pancreatic β-cells: Mechanism and glucose dependence. Diabetes, Obesity and Metabolism.
Vlckova, V., et al. (2010). Hypoglycaemia with pioglitazone: Analysis of data from the Prescription-Event Monitoring study. Journal of Evaluation in Clinical Practice.
You and Your Hormones. (2021). Insulin. Society for Endocrinology.
