Table of Contents
Introduction: Understanding the Growing Concern
Semaglutide is a medicine that has become very popular in recent years. It is used to help people with type 2 diabetes lower their blood sugar. It is also approved for weight loss in people who have obesity or other health conditions. Some brand names of semaglutide are Ozempic, Wegovy, and Rybelsus. These drugs work by copying a hormone in the body called GLP-1, which helps control blood sugar and makes people feel full sooner when they eat.
As more people use semaglutide, some serious health questions have started to come up. One of the biggest concerns is whether semaglutide could lead to a dangerous condition called ketoacidosis. Ketoacidosis happens when the body builds up too many acids, called ketones, in the blood. This condition is most common in people with diabetes, especially when they do not have enough insulin in their bodies. It can lead to coma or even death if not treated quickly.
More recently, doctors have also started talking about a version of this condition called euglycemic diabetic ketoacidosis, or euDKA. In this form, the person’s blood sugar may not be very high, which makes it harder to notice. Some people using semaglutide have reported symptoms of ketoacidosis or euDKA. Because of this, patients, families, and health professionals are asking if there is a real link between semaglutide and ketoacidosis or if the risk is very small.
Part of the reason for the concern is how semaglutide affects the body. This drug lowers appetite, causes weight loss, and slows down how fast food moves through the stomach. Some people eat much less than usual while taking it. Others follow low-carbohydrate diets while also taking semaglutide, especially for weight loss. When the body does not get enough food—especially enough sugar or carbs—it may begin to break down fat for energy. When this happens, ketones are made. If too many ketones build up, ketoacidosis can occur.
Another reason for the worry is that more people without diabetes are now taking semaglutide to lose weight. These people may not be as closely watched by doctors for blood sugar changes or signs of ketone buildup. If they start to feel sick, the cause may be missed. Some may not know the warning signs of ketoacidosis. Others may think the nausea or vomiting is just a normal side effect of the medicine. In some rare cases, this has led to delayed treatment and worse outcomes.
Doctors and scientists are studying this issue closely. At this time, ketoacidosis linked to semaglutide use seems to be rare, but it is not fully understood. The risk may be higher in certain people. These may include people who have type 1 diabetes, those who stop using insulin too soon, or those who are on other medicines like SGLT2 inhibitors. There may also be risks when semaglutide is used with strict dieting, fasting, or long-term illness.
The goal of this article is to explain what is known so far about the link between semaglutide and ketoacidosis. It will answer some of the most common questions people ask online, like whether semaglutide can cause ketoacidosis, who is at risk, what symptoms to watch for, and how to stay safe while taking the drug. The information comes from medical studies, case reports, and health safety alerts. It is written in a clear and simple way so that anyone—whether a patient, caregiver, or health worker—can understand the key facts.
As semaglutide continues to be used by more people around the world, knowing the possible side effects becomes more important. While the benefits of the drug are clear, especially for diabetes and obesity, even rare risks must be taken seriously. Understanding how the drug works, what it can do to the body, and how to spot early warning signs of trouble can help prevent serious problems. Clear knowledge helps people make safer decisions with their doctors.
What Is Semaglutide and How Does It Work?
Semaglutide is a medicine that helps lower blood sugar and reduce weight. It is used mainly for people with type 2 diabetes and for those who need help losing weight. Semaglutide belongs to a group of drugs called GLP-1 receptor agonists. These drugs work by copying the action of a hormone in the body called glucagon-like peptide-1 (GLP-1).
GLP-1 is a hormone made in the gut after eating. It helps the body manage blood sugar. Semaglutide copies this natural hormone, which helps improve blood sugar levels and decreases hunger.
How Does Semaglutide Work in the Body?
Semaglutide works in three main ways:
- Helps the body release insulin:
Insulin is a hormone that lowers blood sugar. Semaglutide helps the pancreas release insulin when blood sugar levels are high. It does not make the body produce too much insulin, which helps prevent low blood sugar in most cases. - Slows down stomach emptying:
Semaglutide makes the stomach empty food more slowly. This helps blood sugar rise more slowly after meals. It also helps people feel full longer, which often leads to eating less. - Reduces glucagon levels:
Glucagon is a hormone that raises blood sugar by telling the liver to release sugar. Semaglutide lowers glucagon levels, which keeps blood sugar from getting too high.
Together, these actions help control both blood sugar and appetite.
What Forms of Semaglutide Are Available?
Semaglutide comes in three main forms:
- Ozempic – A once-weekly injection used to treat type 2 diabetes.
- Rybelsus – A daily pill also used for type 2 diabetes.
- Wegovy – A once-weekly injection approved for weight loss in people who have obesity or are overweight with weight-related health problems.
All three types work the same way, but they come in different forms and doses depending on why they are being used.
Who Uses Semaglutide?
Doctors prescribe semaglutide to people with type 2 diabetes who need help lowering their blood sugar. It is often used when diet, exercise, or other medicines are not enough. In some cases, it is used with other diabetes medicines, such as metformin or insulin.
Semaglutide is also used by people without diabetes for weight loss. Wegovy, the weight-loss version, is approved for people who are obese or overweight and have health risks like high blood pressure or heart problems.
The dose for weight loss is usually higher than the dose used for diabetes. This higher dose helps reduce appetite more and leads to greater weight loss.
How Is Semaglutide Different from Insulin?
Semaglutide is not the same as insulin. It does not replace insulin in the body. Instead, it helps the body use insulin better and tells the pancreas to make more insulin only when needed. Because of this, semaglutide usually does not cause low blood sugar (hypoglycemia) unless it is used with insulin or certain other diabetes medicines.
What Are the Common Side Effects?
Semaglutide may cause some side effects, especially when starting the medicine or when the dose is increased. Common side effects include:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Loss of appetite
These side effects often go away after a few weeks. The slowed digestion caused by semaglutide can sometimes lead to dehydration or other problems if not managed properly.
Why Understanding Semaglutide Matters
More people are using semaglutide, not just for diabetes but also for weight loss. It works in many helpful ways—by lowering blood sugar, slowing digestion, and reducing hunger. However, its strong effects on the body’s metabolism also raise new questions. Some concerns, such as the risk of ketoacidosis, may be linked to the way semaglutide changes how the body uses energy, especially in certain situations. Understanding how the drug works helps explain why these concerns have come up and who may be at higher risk.
What Is Diabetic Ketoacidosis (DKA) and How Is It Typically Caused?
Diabetic ketoacidosis (DKA) is a serious and life-threatening problem that happens when the body does not have enough insulin. Without insulin, the body cannot use sugar (glucose) for energy. Instead, it starts breaking down fat. This creates acids in the blood called ketones. When too many ketones build up, the blood becomes too acidic, which can be dangerous and even deadly if not treated.
What Happens in the Body During DKA?
Insulin is a hormone that helps move glucose from the blood into the cells. Glucose is the body’s main source of energy. When insulin is missing or very low, glucose stays in the blood, and cells do not get the energy they need. The body thinks it is starving, so it starts to burn fat to make energy.
When fat is broken down, the body makes ketones as a byproduct. Ketones are normally used in small amounts for energy. But during DKA, the body makes too many ketones too fast. These ketones enter the bloodstream and cause the blood to become acidic. This condition is called ketoacidosis.
Who Is Most at Risk for DKA?
DKA is most common in people with type 1 diabetes. In type 1 diabetes, the body makes little or no insulin. These people must take insulin every day. If they miss a dose or do not take enough insulin, DKA can happen quickly.
People with type 2 diabetes can also get DKA, but it is less common. It usually happens if they are very sick, have an infection, or take medications that lower insulin too much.
What Can Trigger DKA?
Several things can trigger DKA. Some of the most common causes include:
- Missed insulin doses: Forgetting or skipping insulin shots or problems with an insulin pump
- Infections: Like the flu, pneumonia, or urinary tract infections that cause stress in the body
- Physical stress: Surgery, heart attack, or severe illness
- Medications: Some medicines, like steroids or diuretics, can raise blood sugar or make insulin less effective
- Other problems: Not eating enough, being dehydrated, or drinking alcohol
When the body is under stress or fighting an infection, it releases hormones like cortisol and adrenaline. These hormones raise blood sugar and make insulin work less effectively. This leads to high blood sugar and ketone buildup, which causes DKA.
How Is DKA Diagnosed?
Doctors check for three main things when diagnosing DKA:
- High blood sugar: Usually over 250 mg/dL, though it may be lower in some cases
- Ketones in the blood or urine: A sign the body is burning fat instead of sugar
- Acidic blood: A low pH level in the blood shows that the blood is too acidic
Blood tests can also check for electrolyte levels, dehydration, and kidney function. These help doctors decide how serious the DKA is and what treatment is needed.
What Are the Symptoms of DKA?
Symptoms of DKA usually start quickly and get worse without treatment. These may include:
- Nausea or vomiting
- Stomach pain
- Deep or fast breathing
- Dry mouth and thirst
- Fruity-smelling breath
- Weakness or confusion
- Frequent urination
In severe cases, DKA can cause unconsciousness or even death. It is a medical emergency and needs treatment right away in a hospital.
What Is Euglycemic DKA?
Sometimes, a person has all the signs of DKA, but their blood sugar is not very high. This is called euglycemic DKA or euDKA. It can be harder to notice because blood sugar levels may seem normal.
Euglycemic DKA can happen in people taking certain diabetes drugs called SGLT2 inhibitors. It can also occur in people who are not eating enough, are on a strict low-carb or ketogenic diet, or are fasting for long periods. These situations lower blood sugar but still cause the body to make ketones.
Why Early Treatment Matters
DKA is dangerous but treatable. Hospitals treat DKA with:
- Insulin: To lower blood sugar and stop the body from making ketones
- Fluids: To fix dehydration
- Electrolytes: To balance important minerals in the blood
Most people get better within a day or two if treated early. Waiting too long can lead to coma or death. That is why it is important to know the warning signs and act fast.
DKA is a serious complication of diabetes caused by low insulin levels. It leads the body to burn fat instead of sugar, which creates ketones and causes the blood to become too acidic. Common triggers include missed insulin, infection, illness, or certain medications. Understanding the causes, symptoms, and dangers of DKA helps people with diabetes—and their healthcare providers—take steps to prevent it and treat it quickly when it occurs.
What Is Euglycemic DKA and Why Does It Matter?
Euglycemic diabetic ketoacidosis, often shortened to euDKA, is a rare but serious medical condition. It shares many features with typical diabetic ketoacidosis (DKA), but with one major difference: blood sugar levels in euDKA are not very high. This can make it harder to recognize and treat quickly.
In most cases of DKA, the blood sugar level is very high, usually above 250 mg/dL. This is one of the main signs that alerts doctors to the condition. However, in euDKA, blood sugar can stay normal or only slightly elevated—usually below 250 mg/dL. This can confuse both patients and healthcare providers. They might think the symptoms are caused by something else and not consider ketoacidosis as the cause.
How Euglycemic DKA Happens
To understand euDKA, it helps to look at how regular DKA develops. In people with diabetes, especially type 1 diabetes, the body cannot make enough insulin. Insulin helps move sugar from the blood into the cells to be used for energy. Without insulin, the body thinks it is starving, even if blood sugar is high. As a result, it starts breaking down fat for energy. This process creates ketones, which are acids. If too many ketones build up in the blood, it leads to ketoacidosis.
In euDKA, the same process happens, but without high blood sugar. This can occur when someone is not eating enough carbohydrates, is dehydrated, or is taking certain medications. These factors can cause the body to shift into fat-burning mode, producing ketones even when blood sugar is not very high.
Why Euglycemic DKA Is Harder to Detect
Because blood sugar is not very high, euDKA can be overlooked. Many of the usual warning signs of DKA, like extreme thirst and frequent urination, may not be as strong. Patients might still feel very sick, with symptoms such as nausea, vomiting, stomach pain, tiredness, and rapid breathing. But without the high blood sugar, doctors may not think of ketoacidosis right away. This delay can be dangerous because euDKA can still lead to serious complications, including coma or death if not treated quickly.
Who Is at Risk for Euglycemic DKA?
Certain groups of people have a higher risk of developing euDKA. People with type 1 diabetes are at the highest risk, especially if they are not taking enough insulin. However, euDKA has also been seen in people with type 2 diabetes, and even in those without diabetes, under certain conditions.
One key risk factor is the use of certain diabetes medications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to increase the risk of euDKA. These drugs lower blood sugar by helping the kidneys remove glucose through urine. Because they keep blood sugar levels low, even when insulin levels drop, the typical signs of DKA may be hidden.
Other risk factors include long periods of fasting, very low-carbohydrate or ketogenic diets, pregnancy, alcohol abuse, and infections. All of these can push the body into a state where it starts burning fat instead of sugar for energy. This increases ketone production and raises the risk of ketoacidosis, even if blood sugar remains in a normal range.
Relevance to Semaglutide
Semaglutide does not directly cause euDKA, but there are reasons it may be linked to it in some cases. Semaglutide slows down how quickly the stomach empties. This can lead to nausea and vomiting, which may cause people to eat less and become dehydrated. If someone is also on a low-carb diet or fasting for weight loss, their body may shift to using fat for energy. In rare cases, this could lead to a buildup of ketones and trigger euDKA.
In addition, if a person with diabetes starts semaglutide and reduces their insulin without medical guidance, this can increase the risk of developing euDKA. The body needs enough insulin to prevent ketone buildup. If insulin is reduced too much, ketone production may rise, even if blood sugar levels stay near normal.
Why It Matters
Understanding euDKA is important because it can be overlooked. Healthcare providers must be aware that ketoacidosis can happen even without very high blood sugar. Patients should also be aware of the symptoms, especially if they are taking medications like semaglutide, are on low-carb diets, or have other risk factors. Early recognition and treatment are key to preventing serious harm.
Is There a Proven Link Between Semaglutide and Ketoacidosis?
Semaglutide is widely used to help manage blood sugar in people with type 2 diabetes and for weight loss in people with obesity. It works by copying the effects of a natural hormone called GLP-1, which helps the body produce more insulin and slows digestion. Most people who use semaglutide do not develop serious side effects. However, some reports have raised questions about whether this medication might cause a dangerous condition called diabetic ketoacidosis (DKA), especially in certain situations.
To understand if there is a real link between semaglutide and ketoacidosis, researchers and doctors have looked at different types of information. This includes data from large clinical trials, case reports from doctors, and safety monitoring systems run by health agencies.
Clinical Trial Data
Before semaglutide was approved, it was tested in many large clinical trials. These trials included people with type 2 diabetes and those with obesity. In these studies, semaglutide did not show a clear link to causing diabetic ketoacidosis. The condition was not reported as a common side effect, even among people with diabetes who were using insulin along with semaglutide. Because these trials are done in controlled settings with close medical monitoring, it is less likely for rare or unexpected problems to occur during the study period. This makes it hard to catch rare events like DKA unless the study is very large and lasts for many years.
Case Reports and Real-World Evidence
Even though large trials did not find a strong link between semaglutide and DKA, individual case reports have suggested that it may be possible in some situations. A case report is a detailed story written by a doctor about something unusual that happened to one or more patients. In recent years, a small number of case reports have described people developing DKA or euglycemic DKA (a type of ketoacidosis without high blood sugar) while taking semaglutide.
In most of these cases, the patients were either taking insulin or had changed their diet in a way that made them eat very few carbohydrates. Some people stopped taking their insulin or lowered the dose too much after starting semaglutide, which may have led to DKA. Others were following a strict ketogenic or fasting diet, which may have caused their body to make too many ketones. When ketones build up in the blood, it can lead to ketoacidosis.
It is important to remember that a case report does not prove that the medication caused the problem. Other things, like a change in insulin use, an infection, or a sudden illness, may have played a role. Still, case reports are helpful because they raise awareness about rare risks that might not show up in clinical trials.
Safety Monitoring Systems
Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) run systems that collect reports of possible drug side effects. These reports come from doctors, hospitals, and even patients. After semaglutide became available to the public, a few reports of DKA were sent to these agencies. However, the number of reports has been small compared to the millions of people who use the drug.
These reports often do not include full details, such as the person’s health history, what other medications they were taking, or what triggered the event. Because of this, the FDA and EMA have not issued a formal warning saying semaglutide directly causes DKA. Instead, they advise careful monitoring, especially in people with diabetes who are adjusting insulin or who are on a very low-carb diet.
Comparing with Other Diabetes Medications
Some diabetes medications, like SGLT2 inhibitors (for example, empagliflozin or canagliflozin), are known to raise the risk of ketoacidosis. These drugs have a clear warning label for this risk. Semaglutide does not belong to the same class of drugs and does not work the same way. Based on the current data, the risk of DKA with semaglutide appears to be much lower, and possibly only seen in rare or high-risk situations.
Doctors have also compared the number of DKA cases in people taking semaglutide versus those taking other medications. So far, the data suggest that semaglutide does not lead to more DKA cases than other commonly used treatments for diabetes.
There is no strong proof from clinical trials that semaglutide directly causes ketoacidosis. However, case reports and safety monitoring suggest that rare cases may happen, especially in people who stop insulin too quickly, follow extreme diets, or have other risk factors. Health authorities continue to watch for new cases and may update guidelines if needed. For now, the overall risk appears low, but some people may need extra care when starting this medication.
What Are the Proposed Mechanisms Behind Ketoacidosis with Semaglutide Use?
Semaglutide is a medication that works by copying a natural hormone in the body called GLP-1 (glucagon-like peptide-1). This hormone helps control blood sugar, slows down digestion, and reduces appetite. Because of these effects, semaglutide is often used by people with type 2 diabetes or by those who want to lose weight. However, some healthcare professionals have raised concerns about a rare but serious condition called ketoacidosis, which may happen in certain people taking semaglutide. To understand how this might happen, it helps to look closely at what semaglutide does to the body.
Reduced Caloric and Carbohydrate Intake
Semaglutide strongly reduces hunger, so people who take it often eat much less food. In many cases, they also start eating fewer carbohydrates because they either lose their appetite or follow popular low-carb or ketogenic diets to boost weight loss. Carbohydrates are the body’s main source of glucose, which fuels muscles, the brain, and other organs. When the body doesn’t get enough carbohydrates, it starts using fat for energy. This process creates chemicals called ketones.
A small amount of ketones is normal and safe. But if the body keeps breaking down fat at a high rate—especially without enough insulin—ketones can build up in the blood. This leads to a condition called ketoacidosis, where the blood becomes too acidic. When semaglutide causes people to eat far fewer calories and carbs, it may increase the risk of this chain reaction, especially in people who already have low insulin levels.
Delayed Gastric Emptying and Insulin Suppression
Another way semaglutide affects the body is by slowing down how quickly food leaves the stomach. This is called delayed gastric emptying. It helps people feel full longer, but it also changes how the body digests food and absorbs nutrients. With slower digestion, the body may make less insulin in response to food. Insulin is a hormone that helps move sugar from the blood into the body’s cells. If insulin levels drop too low, the body may begin to use fat as fuel even when it’s not necessary. That can lead to more ketone production.
Also, semaglutide may lead to less need for insulin or cause some patients to reduce their insulin dose too much. People with diabetes who use insulin might lower their doses or skip injections because their blood sugar seems better. But if the body still needs insulin to process food or prevent ketone buildup, taking less can be dangerous. Even without high blood sugar, a drop in insulin can trigger ketoacidosis. This is known as “euglycemic” diabetic ketoacidosis, where blood sugar levels stay normal or only slightly elevated, making it harder to spot.
Overlap with Ketogenic Dieting or Prolonged Fasting
Some people who take semaglutide also follow a ketogenic diet or fast for long periods. A ketogenic diet is high in fat and very low in carbohydrates. While it may lead to weight loss, it also causes the body to stay in a constant state of ketosis, where it burns fat and produces ketones. Combining this type of diet with semaglutide increases the chance that ketones may rise to dangerous levels, especially if the person also has diabetes or insulin problems.
Fasting can also add to the risk. When people skip meals or go many hours without eating while taking semaglutide, their body may switch to fat burning quickly. If insulin is too low, or if there are other health stressors, this can cause ketones to rise quickly, leading to ketoacidosis. The longer the fast, the higher the risk, especially if the person becomes dehydrated or has an infection at the same time.
Dehydration and Metabolic Stress as Contributing Factors
Semaglutide may also cause side effects like nausea, vomiting, or diarrhea. These side effects can lead to dehydration, which means the body loses too much water. When dehydrated, the body cannot get rid of ketones as well through the kidneys. As ketones build up in the blood, the risk of ketoacidosis increases.
In some cases, people taking semaglutide may already be under stress from illness, surgery, or other medical conditions. These stressors can affect how the body uses insulin and how well it controls blood sugar and fat metabolism. This situation can make it easier for ketoacidosis to develop, especially if other risk factors are present, like low-carb eating, fasting, or reduced insulin doses.
While semaglutide is a helpful medicine for many people, there are several ways it may increase the risk of ketoacidosis in certain situations. Reduced food intake, especially fewer carbohydrates, delayed digestion, and lower insulin levels all play a role. People who fast or follow a very low-carb diet may face added risks. Dehydration and stress on the body can also make things worse. Understanding these effects can help patients and healthcare providers stay alert and reduce the risk of serious complications.
Who Is at Higher Risk of Developing DKA While on Semaglutide?
Diabetic ketoacidosis (DKA) is a serious medical condition. It usually happens when the body does not have enough insulin. This causes the body to break down fat for energy, which creates acids called ketones. When these ketones build up in the blood, they can make the blood too acidic. DKA is more common in people with diabetes, but it can happen to others under certain conditions. Some people using semaglutide may be more likely to develop DKA, especially if other risk factors are present.
Several groups of patients may face a higher risk.
People With Type 1 Diabetes
Semaglutide is not approved for type 1 diabetes. However, some people with type 1 diabetes may use it off-label to help control weight or reduce insulin needs. These patients are already at a higher risk for DKA because their bodies do not make insulin. If semaglutide is used and insulin doses are reduced too much, the body may not have enough insulin to prevent ketone buildup. This can lead to DKA, even if blood sugar levels are not very high. This type is called euglycemic DKA (euDKA), and it can be harder to detect.
Even small changes in insulin levels can lead to problems in people with type 1 diabetes. Missing a dose, taking too little, or adjusting insulin without medical advice can all increase the risk of DKA while using semaglutide.
People With Type 2 Diabetes Who Use Insulin
People with type 2 diabetes usually make some insulin, but their bodies do not use it well. Some of them need insulin injections to help control their blood sugar. If these patients start semaglutide, they may lose weight quickly or eat less food. These changes can lower the need for insulin. However, if insulin is stopped or reduced too much and too quickly, there may not be enough insulin to keep ketone levels safe. This can lead to DKA, especially in those who have had diabetes for a long time and have poor insulin production.
Doctors usually advise making insulin changes slowly and only under supervision. If insulin doses are cut too early when starting semaglutide, the body may not be able to handle the changes, especially if food intake drops a lot.
People Taking SGLT2 Inhibitors With Semaglutide
SGLT2 inhibitors are another type of diabetes medicine. These include drugs like canagliflozin, dapagliflozin, and empagliflozin. They help the body get rid of sugar through urine. While effective, they are known to slightly increase the risk of DKA and euDKA. When combined with semaglutide, the chance of DKA may go up, especially in people who reduce food or insulin.
Both drugs can lead to weight loss and lower blood sugar, but the body still needs insulin to prevent ketones. The combination can cause symptoms like nausea and vomiting, which may be confused with common side effects and not recognized as early signs of DKA.
People on Low-Carb or Ketogenic Diets
Some people who take semaglutide also follow very low-carb diets or ketogenic diets to lose weight. These diets reduce the amount of glucose in the body and push it to burn fat instead. This leads to ketone production, which is a normal part of ketosis. However, when semaglutide is added, the combination of reduced eating, lower glucose levels, and insulin suppression may trigger too many ketones. This can shift safe ketosis into dangerous ketoacidosis.
The body needs insulin to safely handle fat breakdown. Without enough insulin or carbohydrate intake, ketones can build up too quickly. Semaglutide slows down digestion and can reduce hunger, which may lead to even lower food intake. This can make the risk of DKA higher when paired with extreme dieting.
People Fasting or With Severe Illness
Periods of fasting, long illnesses, or stomach issues like vomiting and diarrhea can raise the risk of DKA. Semaglutide can cause nausea, vomiting, and poor appetite in some people. If food and fluids are not taken in, and insulin is not adjusted correctly, this can result in dehydration and high ketone levels.
Stress from illness also increases the body’s need for insulin. If insulin is not raised during stress or sickness, this can cause DKA. People using semaglutide may not feel like eating or drinking, and if insulin is skipped during these times, the body can enter DKA quickly.
People Who Lose Weight Rapidly
Rapid weight loss, especially in people with diabetes, may signal changes in metabolism. When weight drops quickly, insulin needs can change. If insulin is not adjusted safely, or if food intake becomes too low, ketone levels may rise. Semaglutide often causes fast weight loss in the first few weeks, which increases the chance of imbalances in sugar, insulin, and fat breakdown.
People losing a lot of weight may also skip meals or eat very little. If they still use insulin, doses may become too high, or if they stop insulin, the body may not have enough to prevent DKA. Rapid weight loss should be monitored closely with regular check-ins and lab tests.
Certain groups of people using semaglutide are more likely to develop DKA. These include people with type 1 diabetes, insulin-using type 2 diabetes, those on SGLT2 inhibitors, those following ketogenic diets, and anyone with poor food intake or dehydration. Careful planning, regular monitoring, and safe insulin management are key to reducing the risk.
Can Semaglutide Cause DKA in People Without Diabetes?
Semaglutide is a medication that helps lower blood sugar and reduce appetite. It was first made for people with type 2 diabetes. Now, it is also used to help people lose weight, even if they do not have diabetes. While semaglutide has many benefits, there are concerns about a rare but serious condition called diabetic ketoacidosis, or DKA.
DKA usually happens in people with diabetes, especially when their bodies do not have enough insulin. Insulin is a hormone that helps sugar enter the cells for energy. When there is not enough insulin, the body starts breaking down fat for fuel. This process releases chemicals called ketones. If ketones build up in the blood, they can make the body very acidic, which can lead to DKA.
Some recent reports suggest that DKA can happen in people who do not have diabetes and are using semaglutide. These cases are very rare, but they raise important questions. It is important to understand how semaglutide might lead to this problem and who could be at risk.
How Semaglutide May Contribute to DKA Without Diabetes
Semaglutide works by copying a natural hormone in the body called GLP-1. This hormone helps control blood sugar, makes people feel full, and slows down how fast food leaves the stomach. When semaglutide is used for weight loss, it can reduce how much a person eats by a lot. Some people may eat very few calories or follow strict diets like the ketogenic diet, which is high in fat and very low in carbohydrates.
When the body does not get enough carbohydrates, it turns to fat for energy. This fat-burning process produces ketones. In normal amounts, ketones are not harmful. But if the body makes too many ketones, the blood becomes acidic. This is how DKA can happen, even if blood sugar levels are normal. This is called euglycemic DKA, or euDKA.
Semaglutide may increase the chance of euDKA in people who do not have diabetes if:
- They eat very few carbohydrates
- They fast for long periods
- They lose weight quickly
- They become dehydrated
- They are already at risk for low insulin levels
These changes can make the body act like it is in a state of starvation. The liver then produces more ketones, which increases the chance of DKA.
What the Reports Say
There are some case reports of people who developed DKA while using semaglutide for weight loss and who had no history of diabetes. In most of these cases, the people were following very low-calorie or low-carb diets. Some were fasting. Others had recently lost a lot of weight.
Even though these reports are rare, they are important because they show that semaglutide may lead to serious side effects in some people without diabetes—especially when used with extreme dieting or fasting.
Why Non-Diabetics Should Still Be Cautious
People without diabetes do not usually have problems with insulin. However, in some situations, even they can have low insulin levels. This might happen with extreme diets or during times of illness, stress, or dehydration. When combined with semaglutide, these conditions might increase the risk of DKA.
People using semaglutide for weight loss may also ignore or misread the warning signs of DKA. Symptoms like nausea, vomiting, and stomach pain may seem like common side effects of the drug. However, they can also be early signs of DKA.
Signs to Watch For
Common warning signs of DKA include:
- Nausea and vomiting
- Stomach pain
- Fruity-smelling breath
- Trouble breathing
- Feeling very tired or confused
If these symptoms appear, medical help is needed right away. Even in people without diabetes, early treatment can prevent serious problems.
While semaglutide is not known to directly cause DKA in people without diabetes, it may play a role under certain conditions. Eating too few calories, following very low-carb diets, fasting, or rapid weight loss may lead to changes in the body that increase the risk of DKA. Health professionals should be aware of this possible risk, and patients should be educated about the warning signs. Monitoring and early care are the best ways to stay safe.
What Symptoms Should Prompt Concern for DKA in Patients Using Semaglutide?
Diabetic ketoacidosis (DKA) is a serious and potentially life-threatening condition. It happens when the body starts breaking down fat too quickly, which causes a buildup of acids in the blood called ketones. While DKA is usually seen in people with diabetes, it has also been reported in some people using semaglutide. Knowing the warning signs is important to help catch the problem early.
Common Symptoms of DKA
Some symptoms of DKA can appear slowly over a few hours or days. The most common signs include:
- Nausea and vomiting: People may feel very sick to their stomach or vomit often. This can also lead to dehydration, which makes the situation worse.
- Abdominal pain: Stomach pain or discomfort is a frequent complaint in DKA and can be mistaken for other problems like food poisoning or stomach flu.
- Rapid breathing: Breathing may become deep and fast. This is the body’s way of trying to fix the acid level in the blood.
- Fruity-smelling breath: A sweet, fruity smell on the breath is a clear sign of too many ketones.
- Extreme tiredness or confusion: People with DKA often feel very weak or sleepy. Some may become confused or even pass out.
- Dry mouth and thirst: Dehydration happens quickly because of fluid loss from vomiting or high levels of sugar in the blood.
These symptoms may look like common side effects of semaglutide, such as nausea or tiredness, but they can mean something more serious.
Overlapping Symptoms with Semaglutide Side Effects
Semaglutide often causes mild side effects, especially when treatment starts. These may include nausea, vomiting, and a lack of appetite. Because these symptoms are also common in early DKA, it may be easy to ignore or overlook them. For example, someone using semaglutide might think they just have a stomach issue caused by the medicine, when in fact their body could be entering ketoacidosis.
That’s why it’s important to look at the whole picture. If symptoms like vomiting, fatigue, or stomach pain last more than a day, or get worse over time, DKA could be developing. If other symptoms like fast breathing or fruity breath also appear, the concern becomes more serious.
When to Test for Ketones
Ketones are chemicals the body makes when it burns fat for energy. In normal amounts, they are not harmful. But in large amounts, they can cause the blood to become too acidic. Testing for ketones can help show whether the body is entering a dangerous state.
People with diabetes, especially those on insulin, should check their ketones if they:
- Are vomiting or cannot keep food or fluids down
- Feel very tired or confused
- Have a high blood sugar level that won’t come down
- Are losing weight quickly or eating very little
- Have signs of infection or illness
Blood ketone meters are the most accurate way to check ketones. Urine ketone test strips are also available and can show if the body is burning fat too fast. These tests can be done at home and help detect early signs of DKA.
Even people without diabetes who are using semaglutide should pay attention if they are losing a lot of weight quickly, eating very few carbohydrates, or following a strict diet. In some rare cases, DKA has been reported in non-diabetic users who are on low-carb or ketogenic diets while taking semaglutide.
When to Seek Immediate Medical Help
If someone has several of the symptoms mentioned and cannot eat or drink, or if they feel very ill, medical attention is needed right away. DKA can worsen quickly, and waiting too long can make treatment harder.
Doctors will usually test the blood for ketones, glucose levels, and acid balance. Treatment may include fluids through an IV, insulin, and careful monitoring in a hospital setting.
Knowing the warning signs of DKA can make a big difference. Even though the risk of DKA with semaglutide is low, it’s important to take symptoms seriously, especially when they last more than a day or involve more than just nausea. Early testing and treatment can prevent serious outcomes.
What Should Clinicians and Patients Do to Minimize Risk?
Semaglutide is widely used to help manage blood sugar and reduce weight. While it is considered safe for most people, there is a small chance of developing diabetic ketoacidosis (DKA), especially in certain situations. Understanding how to reduce this risk can help keep patients safe and improve treatment outcomes.
Patient Education Is Key
One of the most important ways to lower the risk of DKA is through good education. Patients need to know how semaglutide works and what side effects to expect. They should understand that nausea and vomiting may happen, but these should not be ignored if they continue or become severe. When these symptoms occur, people may eat less, drink less, and stop taking insulin. This combination can lead to DKA, especially in people with diabetes.
Patients should be taught the signs of DKA. These include:
- Trouble breathing
- Feeling very tired or weak
- Stomach pain or nausea
- A fruity smell on the breath
- Confusion or feeling dizzy
If these symptoms show up, it may be a medical emergency. Teaching people what to look for can help them get care early and avoid serious problems.
Insulin Doses Must Be Managed Carefully
People who take semaglutide and also use insulin must be careful not to lower their insulin dose too much. As semaglutide helps lower blood sugar, some may think they no longer need insulin or can cut back a lot. But the body still needs some insulin to prevent DKA, especially for people with type 1 diabetes or those who have used insulin for many years.
A health care provider should always help adjust insulin doses. Insulin should never be stopped suddenly unless the doctor gives clear instructions. Even if blood sugar is normal, the body may still need insulin to stop the build-up of ketones.
Watch for Drug Combinations
Some people may take other drugs that raise the risk of DKA, such as SGLT2 inhibitors (like empagliflozin or canagliflozin). These drugs can increase ketones in the blood, especially when combined with semaglutide. Health care providers should check all medications a patient is taking. If two or more drugs increase DKA risk, closer monitoring may be needed.
Diet and Nutrition Choices Matter
Low-carb or ketogenic diets are popular among people trying to lose weight. But when combined with semaglutide, these diets may increase the chance of DKA. Eating too few carbohydrates can cause the body to burn fat instead of sugar for energy. This fat-burning process makes ketones. High levels of ketones may lead to ketoacidosis if insulin levels are also low.
Doctors and dietitians should help patients choose a balanced eating plan. It is safer to include some healthy carbohydrates while using semaglutide, especially for people with diabetes or those taking insulin.
Fasting or skipping meals can also be risky. If someone is not eating and also feeling sick from semaglutide, they may not drink enough water or get enough calories. This can lead to dehydration and increase ketone levels. Drinking plenty of fluids and eating small meals regularly can help prevent this.
Know When to Test for Ketones
Ketone testing is simple and can help catch early signs of DKA. Blood ketone meters or urine ketone test strips are available in most pharmacies. Testing should be done if a person is:
- Feeling sick or vomiting
- Eating very little or not at all
- Running a fever or has an infection
- Seeing a drop in insulin doses
Health care providers should teach patients how to use ketone tests and when to use them. Early detection can stop DKA from becoming severe.
Better Communication Between Providers
Patients often see different doctors for diabetes, weight loss, and other health needs. It is important that all providers work together when someone is using semaglutide. For example, a diabetes specialist should know if a patient is also seeing a weight loss doctor or taking other new medications. Clear notes in the patient’s health record can help all providers stay informed and avoid harmful drug combinations or advice.
When possible, pharmacists should also be included in the care team. They can check for drug interactions and educate patients on how to use medications safely.
Staying Safe with Semaglutide
Semaglutide offers many health benefits, but safety depends on using it the right way. Education, careful insulin management, attention to diet, and strong communication between health professionals can lower the risk of ketoacidosis. With the right support, most patients can use semaglutide successfully and avoid serious complications.
Are There Guidelines or Recommendations on Semaglutide and DKA Risk?
Semaglutide is a medication that helps control blood sugar levels and support weight loss. It is often used in people with type 2 diabetes and is also approved for obesity treatment. However, concerns about a rare but serious condition called diabetic ketoacidosis (DKA) have led to questions about whether there are clear safety guidelines or recommendations for using semaglutide—especially when the risk of DKA is present.
Currently, no major diabetes or obesity organizations have issued special guidelines that directly link semaglutide to DKA. However, there are general safety rules from medical groups and health authorities that can help guide doctors and patients in reducing the risk.
Professional Guidelines from Medical Societies
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) provide regular treatment guidelines for managing type 2 diabetes. These guidelines recommend semaglutide as a second-line or third-line therapy, especially for people who are overweight or at risk of heart problems. While DKA is not listed as a common side effect, the guidance does remind healthcare providers to watch for changes in blood sugar levels, particularly when starting or stopping any diabetes medications.
These guidelines also highlight that people who take certain drugs—like SGLT2 inhibitors—may have a higher chance of developing euglycemic DKA. Even though semaglutide is not part of that drug group, it may still increase risk in certain situations, such as low food intake or skipping insulin. Because of this, it’s important for doctors to watch closely for signs of ketosis or DKA in patients who are changing their treatment plans or experiencing other health problems.
Warnings from Drug Manufacturers
The companies that make semaglutide—under brand names like Ozempic, Wegovy, and Rybelsus—have published official drug labels approved by the U.S. Food and Drug Administration (FDA) and other health agencies. These labels do not list DKA as a common side effect, but they do include safety warnings that are helpful.
For example, the label for Ozempic notes that the medication can cause nausea, vomiting, and decreased appetite. These symptoms could lead to dehydration or reduced food intake, both of which are known triggers for DKA. The labeling advises caution when semaglutide is used in combination with insulin or other drugs that affect blood sugar. People who take insulin and suddenly reduce their dose due to weight loss or better blood sugar readings may unintentionally create conditions that increase the chance of ketoacidosis.
Also, the drug label recommends educating patients on the signs and symptoms of serious side effects, including abdominal pain, rapid breathing, and confusion, which may be seen in DKA. Patients are advised to report these symptoms to their healthcare provider right away.
Lack of Specific Guidelines for Non-Diabetic Use
One major gap in current medical guidance involves people without diabetes who are taking semaglutide for weight loss. Since semaglutide is approved for chronic weight management in individuals with or without diabetes, this group is growing. However, most safety guidelines are still focused on diabetes care, and little research has been done on DKA risk in non-diabetic patients.
Some case reports have shown that people without diabetes who follow very low-carb or ketogenic diets while using semaglutide may develop a form of ketoacidosis. Because these patients do not have high blood sugar, it can be harder to recognize the problem early. No official recommendations have been released to guide doctors on how to safely use semaglutide in this population, especially regarding diet and hydration.
Monitoring and Risk Management Strategies
Even without specific rules for every case, healthcare providers can take steps to reduce the risk of DKA. For example, they can:
- Monitor for signs of ketosis, especially during illness or fasting
- Ensure that patients on insulin do not reduce their dose too quickly
- Recommend regular meals and avoid extremely low-carbohydrate diets
- Educate patients to report early symptoms like nausea, vomiting, or shortness of breath
- Review all medications to avoid combining drugs that increase DKA risk
In people with type 1 diabetes, semaglutide is not recommended at all. Using it off-label in type 1 diabetes may lead to insulin dose changes that increase the risk of DKA. This group must be monitored very carefully if semaglutide is used in clinical trials or special situations.
While semaglutide is considered safe and effective for many people, there are still concerns about DKA in some cases. Most professional guidelines do not list semaglutide as a common cause of DKA, but they do stress the importance of watching for metabolic problems. Drug manufacturers have added safety tips to help avoid complications.
Until more data is available, careful monitoring, good communication between healthcare providers, and clear patient education remain the best tools for preventing rare but serious events like ketoacidosis.
Conclusion: Separating Myth from Medical Reality
Semaglutide is a medicine that helps people manage type 2 diabetes and lose weight. It works by acting like a natural hormone in the body called GLP-1. This hormone helps lower blood sugar, slows down how fast food leaves the stomach, and helps people feel full sooner. Because of these effects, semaglutide has become a popular drug for people with diabetes and also for people without diabetes who want to lose weight.
As more people use semaglutide, questions have come up about its safety, especially whether it can cause a serious condition called ketoacidosis. Diabetic ketoacidosis, or DKA, happens when the body makes too many acids called ketones. These acids build up in the blood and can become dangerous. Usually, DKA is linked to high blood sugar and not having enough insulin in the body. It often happens in people with type 1 diabetes who miss insulin doses, get sick, or have other medical problems.
A rare form of DKA called euglycemic DKA, or euDKA, has also become better known. In this type, blood sugar levels are not very high, which can make it harder to spot. EuDKA has been mostly linked to medicines like SGLT2 inhibitors, but it may also happen with semaglutide in some cases.
At this time, there is no strong proof that semaglutide directly causes ketoacidosis in most people. Studies from clinical trials do not show high numbers of DKA cases. However, some case reports and safety reports have raised concern. These reports are rare but suggest that certain people may be more at risk than others. These include people with type 1 diabetes, people who take insulin and lower their dose too much when starting semaglutide, and people on low-carb or ketogenic diets. These factors can lower the amount of insulin in the body and push it into a state where ketones begin to build up.
There are several possible ways semaglutide may raise the risk of ketoacidosis in some cases. One is through reduced food intake. Because semaglutide makes people feel full, some patients eat much less than usual. If this continues for a few days, the body may switch to burning fat for energy, which can raise ketone levels. This is more likely if the person also avoids eating carbohydrates. Another reason is that semaglutide slows down the stomach, which may affect how fast sugar enters the blood. This can also change how much insulin the body needs. In people with diabetes, if insulin doses are cut too much or stopped completely, ketone levels can rise quickly. Dehydration, fasting, illness, or using semaglutide with other drugs like SGLT2 inhibitors may also increase the chances of ketoacidosis.
People without diabetes who take semaglutide for weight loss may also be at risk. Even though they usually do not need insulin, eating very little or using a strict low-carb diet while on semaglutide may lead to high ketone levels. A few reports have shown that euDKA can happen in non-diabetics, especially when they follow intense fasting or ketogenic eating plans while taking semaglutide.
It is important to know the signs of ketoacidosis early. These signs can include nausea, vomiting, stomach pain, tiredness, fast breathing, and fruity-smelling breath. These symptoms may be mistaken for side effects of semaglutide, but they should not be ignored. Testing blood or urine for ketones can help catch the problem early. If ketones are high, medical care is needed right away.
Healthcare professionals can lower the risk by making sure patients understand how semaglutide works. Patients with diabetes need to adjust insulin carefully and never stop it without guidance. People using semaglutide for weight loss should avoid extreme diets unless monitored by a doctor. Drinking enough water, eating regular meals, and checking for signs of illness can also help reduce the risk.
So far, expert guidelines have not listed semaglutide as a major cause of ketoacidosis. Most warnings focus on drugs like SGLT2 inhibitors. But doctors and researchers are watching this issue closely. As more people use semaglutide, more data will help show how common this problem really is. Until then, the best approach is caution and good medical advice.
Semaglutide is a helpful drug for many people, and the chance of ketoacidosis appears to be low for most users. But the risk may be real for some, especially in certain situations. By understanding the causes, watching for warning signs, and working closely with healthcare providers, serious problems can be prevented. This helps patients get the benefits of semaglutide safely while staying protected from rare but serious side effects like ketoacidosis.
Research Citations
Sood, N., Bansal, O., Garg, R., & Hoskote, A. (2024). Euglycemic ketoacidosis from semaglutide in a patient without diabetes. JCEM Case Reports, 2(9), luae156.
Smits, M. M., & van Raalte, D. H. (2021). Safety of semaglutide. Frontiers in Endocrinology, 12, 645563.
Pasqua, M.-R., Tsoukas, M. A., Kobayati, A., Aboznadah, W., Jafar, A., … Haidar, A. (2025). Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: A double-blind, randomized, crossover trial. Nature Medicine, 31, 1239–1245.
Duan, Z., Wei, K., Xue, Z., Li, L., Jin, J., Yang, S., Zhou, J., & Ma, S. (2025). Crowdsourcing-based knowledge graph construction for drug side effects using large language models with an application on semaglutide. arXiv.
Morrison, N., Barnett, K., Tantum, J., … Whalen, M. (2020). A case of euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus and COVID-19. Cureus, 12(12), e12029.
Acosta, A., Fanco, A., Rohan, H., & Elfessi, Z. (2025). Acute pancreatitis and euglycemic non-diabetic ketoacidosis caused by an intentional semaglutide overdose. JEM Reports, 4(1), 100139.
Hughes, K., Sumaruth, Y. R. K., Mohammed, E., & Bakshsingh, V. S. (2024). Acute pancreatitis likely due to semaglutide. Cureus, 16(9), e69844.
Sedghi, A., & Smith, B. (2025). Asymptomatic subcutaneous semaglutide overdose: A case report. Journal of Pharmacy Practice.
Reactions Weekly. (2024). Semaglutide (subcutaneous route): Euglycaemic diabetic ketoacidosis. Reactions Weekly, 2006, 604.
Thaibah, H. A., Banji, O. J. F., Banji, D., & Alshammari, T. M. (2025). Diabetic ketoacidosis and the use of new hypoglycemic groups: Real-world evidence utilizing the Food and Drug Administration Adverse Event Reporting System. Pharmaceuticals, 18(2), 214.
Questions and Answers: Semaglutide and Ketoacidosis
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used to treat type 2 diabetes and obesity by enhancing insulin secretion, suppressing appetite, and slowing gastric emptying.
Ketoacidosis is a serious condition characterized by high levels of ketones and acidity in the blood, most commonly associated with uncontrolled diabetes (diabetic ketoacidosis or DKA).
Semaglutide is not commonly associated with causing ketoacidosis directly. However, if it leads to reduced insulin use or poor glucose management, there may be a risk in insulin-dependent diabetics.
Patients with type 1 diabetes or those with type 2 diabetes who reduce or stop insulin while on semaglutide are at higher risk for ketoacidosis.
Early symptoms include nausea, vomiting, abdominal pain, fruity-smelling breath, rapid breathing, and confusion.
Semaglutide increases insulin secretion and reduces glucagon secretion in a glucose-dependent manner, helping to lower blood sugar.
Because semaglutide can reduce appetite and cause gastrointestinal symptoms, some early signs of ketoacidosis (e.g., nausea, reduced appetite) may be overlooked.
Semaglutide is not approved for use in type 1 diabetes and could pose risks, including ketoacidosis, due to insufficient insulin production in these patients.
Seek immediate medical attention, test blood glucose and ketone levels, and avoid delaying insulin therapy if prescribed.
By closely monitoring blood glucose, ensuring appropriate insulin therapy, educating patients on signs of DKA, and not prescribing semaglutide as a substitute for insulin.
Dr. Melissa VanSickle
Dr. Melissa Vansickle, MD is a family medicine specialist in Onsted, MI and has over 24 years of experience in the medical field. She graduated from University of Michigan Medical School in 1998. She is affiliated with medical facilities Henry Ford Allegiance Health and Promedica Charles And Virginia Hickman Hospital. Her subspecialties include General Family Medicine, Urgent Care, Complementary and Integrative Medicine in Rural Health.