Antidiabetic Drugs
Antidiabetic drugs are medications used to treat diabetes mellitus in humans. These drugs lower blood sugar levels through various mechanisms of action. If accidentally ingested by dogs and cats, these medications can lead to severe poisoning symptoms, with the severity varying depending on the drug class, the amount ingested, and the individual factors of the animal.
Antidiabetic drugs are divided into different classes, which exhibit varying toxicity profiles:
Sulfonylureas (such as glipizide, glibenclamide, glimepiride) stimulate insulin release from the pancreas and represent the most dangerous group for pets, as they can cause severe and prolonged hypoglycemia.
Biguanides (primarily metformin) reduce glucose production in the liver and increase insulin sensitivity without directly boosting insulin secretion. They primarily cause gastrointestinal symptoms and, in severe cases, lactic acidosis.
SGLT2 inhibitors (such as empagliflozin, dapagliflozin) promote the excretion of glucose via the kidneys and can lead to electrolyte imbalances and metabolic disturbances.
GLP-1 receptor agonists (such as exenatide, liraglutide) enhance glucose-dependent insulin secretion and inhibit glucagon release, which can lead to hypoglycemia.
DPP-4 inhibitors (such as sitagliptin, saxagliptin) prolong the action of endogenous incretins and have a lower toxicity potential.
Thiazolidinediones (such as pioglitazone) increase insulin sensitivity and have a moderate toxicity potential.
Insulins and insulin analogs, if incorrectly dosed, lead to rapid and potentially life-threatening hypoglycemia.
The most important facts at a glance
Poisonings by antidiabetic drugs represent a medical emergency in small animal medicine. The various drug classes – sulfonylureas, biguanides, SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, thiazolidinediones, and insulins – exhibit different toxicity profiles and require specific therapeutic approaches.
The most common cause of such poisonings is the accidental ingestion of human medications by pets. Small dog breeds and cats are particularly at risk due to their lower body weight.
Clinical symptoms vary depending on the drug class. While sulfonylureas and insulins primarily lead to severe hypoglycemia with neurological symptoms, metformin poisonings mainly cause gastrointestinal complaints and potentially lactic acidosis.
Diagnosis is based on history, clinical symptoms, and the detection of hypoglycemia. Differentially, other causes for low blood sugar levels must be ruled out.
Therapy includes decontamination measures, glucose supplementation, and symptomatic treatment. In severe poisonings, intensive medical monitoring with regular blood glucose checks is essential.
The prognosis is favorable in most cases with early detection and adequate therapy. Long-term consequences are rare but can occur in the form of neurological deficits during severe hypoglycemic episodes.
Preventive measures such as the safe storage of medications and educating pet owners about potential dangers are crucial to minimize the risk of such poisonings.
Causes, development and progression
Various oral antidiabetic drugs are used in human medicine. Their effects are based on different mechanisms.
- Increased insulin sensitivity
- Increased insulin secretion (direct/indirect)
- Increased sugar excretion
- Reduced sugar absorption/production
In humans, only 50-60% of the ingested amount is absorbed from the intestine, and absorption is completed after approximately 6 hours.
Excretion occurs via the kidneys.
The average plasma elimination half-life is between 1.5 and 4.5 hours, and correspondingly longer with impaired renal function. With intact kidneys, 90% of excretion is completed after 24 hours.
The most common cause of antidiabetic drug poisoning in pets is the accidental ingestion of medications intended for human use. There is an increased risk, especially in households where diabetics live. Typical scenarios include:
Dropped tablets ingested by curious pets. Dogs, in particular, often exhibit indiscriminate eating behavior and can swallow multiple tablets at once.
Unsecured medication packaging that is chewed or bitten through by animals. Blister packs or pill containers, in particular, can be attractive to playful animals.
Improper disposal of medications in household waste accessible to animals.
Medication errors by pet owners who administer their own diabetes medications to their pets without veterinary instruction.
Confusion between human and veterinary medications in animals that actually suffer from and are being treated for diabetes.
The risk of poisoning is influenced by various factors. Small dog breeds and cats are particularly at risk due to their lower body weight, as even small amounts of active ingredients can lead to toxic concentrations. Animals with impaired kidney or liver function have an increased risk of severe poisoning symptoms, as the elimination of the active ingredients may be delayed.
Mechanism of action
Metformin inhibits gluconeogenesis in the liver and increases the insulin sensitivity of cells.
However, it does not increase insulin secretion from the pancreas, so hypoglycemia is not expected in cases of metformin intoxication. Nevertheless, signs of intoxication can occur.
The American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC) in the USA indicates that metformin intoxications are reported, particularly in dogs, but also in cats.
In human medicine, metformin action restricts the formation of glucose from lactate in the liver. Prolonged use can thus lead to lactic acidosis. If renal function is significantly impaired at the same time, the risk of life-threatening intoxication increases.
No information is available for animals regarding this.
In cats, the oral antidiabetic drug glipizide causes a decrease in blood sugar levels in approximately 30% of cases.
Antidiabetic drugs are used in humans to treat diabetes mellitus. Two substance classes are particularly relevant in cases of accidental ingestion by animals:
1. Insulin (Mostly Human Insulin)
Mechanism of Action:
- Stimulates glucose uptake in muscle, liver, and fat cells
- Significantly lowers blood sugar levels, → in case of overdose: severe hypoglycemia
Toxic Effect:
- Hypoglycemia: neurological symptoms (disorientation, ataxia, tremors, seizures, unconsciousness)
- Complication: hypoglycemic coma → potentially fatal
Note: Ingestion of entire insulin pens or multiple units by dogs is particularly dangerous.
2. Oral Antidiabetic Drugs: Sulfonylureas (E.G., Glibenclamide, Glipizide)
Mechanism of Action:
- Stimulate insulin release from pancreatic beta cells regardless of blood sugar levels
- Toxic Effect: pronounced hypoglycemia due to uncontrolled insulin secretion
Effects:
- First symptoms within 1–3 hours after ingestion
- Tremors, lethargy, muscle twitching, seizures
- Life-threatening coma if left untreated
Summary
| Substance Class | Mechanism of Action in Intoxication |
| SSRI | Overstimulation of serotonergic synapses → Serotonin Syndrome |
| TCA | Multireceptor action (serotonergic, adrenergic, anticholinergic, cardiotoxic) → neurological and cardiac symptoms |
| SNRI | Serotonergic and noradrenergic overstimulation → Hypertension, seizures |
| MAO Inhibitors | Increased effect of serotonin, norepinephrine, dopamine → Seizures, hypertension |
| Insulin | Uncontrolled glucose uptake → severe hypoglycemia |
| Sulfonylureas | Excessive insulin release → Hypoglycemia with neurological deficits |
Symptoms of intoxication
Signs of intoxication from metformin ingestion are generally mild in dogs and cats and primarily affect the gastrointestinal tract.
- Anorexia
- Nausea
- Vomiting
- Bloating
- Diarrhea
Intoxications in cats due to glipizide can be significantly more severe as a result of the potential drop in blood sugar.
- severe vomiting
- Diarrhea
- Lethargy
- Hypothermia
- Hypotension
- pale mucous membranes
- tremor in the hind limbs.
The clinical signs of antidiabetic drug poisoning vary depending on the drug class, ingested dose, and time since ingestion. The main symptoms result from the blood sugar-lowering effect of these medications.
In sulfonylurea poisonings, the following symptoms typically occur:
- First signs of hypoglycemia such as weakness, lethargy, and ataxia can appear as early as 30 minutes to 1 hour after ingestion
- Progressive neurological symptoms such as disorientation, behavioral changes, and seizures
- Cardiovascular symptoms such as tachycardia, later bradycardia, and hypotension
- Hypothermia
- In severe cases, coma and death
In metformin poisonings, gastrointestinal symptoms are prominent:
- Anorexia and nausea
- Vomiting and diarrhea
- Dehydration
- In severe poisonings, lactic acidosis can develop, characterized by tachypnea, tachycardia, and increasing weakness
- Unlike other antidiabetic drugs, metformin rarely causes hypoglycemia
SGLT2 inhibitors can cause the following symptoms:
- Polyuria and polydipsia
- Electrolyte imbalances
- Dehydration
- Metabolic acidosis
In insulin poisonings, rapid and severe hypoglycemia occurs:
- Rapid onset of weakness and ataxia
- Muscle tremors
- Behavioral changes up to aggression
- Seizures
- Impaired consciousness up to coma
Especially in cats, the symptomatology can vary, as they sometimes react differently to certain active ingredients than dogs. In glipizide poisonings in cats, in addition to the typical hypoglycemia symptoms, tremor of the hind limbs, pale mucous membranes, and severe vomiting have also been observed.
The severity of symptoms correlates with the extent of the blood sugar drop. Neurological symptoms generally occur at blood sugar levels below 3 mmol/L (54 mg/dL), while levels below 2 mmol/L (36 mg/dL) can be life-threatening.
Diagnosis
The diagnosis of antidiabetic drug poisoning is based on history, clinical symptoms, and laboratory diagnostic examinations. Early and precise diagnosis is crucial for initiating adequate therapy.
Regarding the history, information about possible access to antidiabetic drugs or observed ingestion of such medications is of great importance. Pet owners should, if possible, bring the medication packaging to the veterinarian to identify the active ingredient and dosage.
The clinical examination focuses on vital parameters and neurological status. Symptoms typical of hypoglycemia, such as weakness, ataxia, altered consciousness, or seizures, strengthen the suspicion.
In terms of laboratory diagnostics, blood glucose measurement is central. A significantly lowered blood glucose level (<3 mmol/l or <54 mg/dl) with corresponding history and symptoms is highly suspicious of antidiabetic drug poisoning. Blood glucose measurement should be performed repeatedly to document the course. Other important laboratory parameters include:
- Complete blood count and clinical chemistry for assessing organ function
- Electrolytes (especially potassium)
- Acid-base status and lactate levels (especially in metformin poisonings)
- Kidney values (urea, creatinine) for assessing elimination capacity
In cases of unclear history, toxicological detection of antidiabetic drugs in blood or urine can be helpful, but is often not readily available in practice.
Differentially, other causes of hypoglycemia must be ruled out:
- Insulinoma (neuroendocrine tumor of the pancreas)
- Hepatic diseases with impaired gluconeogenesis
- Hypoadrenocorticism (Addison’s disease)
- Sepsis
- Poisonings with other substances (e.g., xylitol)
- Starvation ketonemia in young animals
Distinguishing between antidiabetic drug poisoning and an insulinoma can be difficult; however, in cases of poisoning, a clear history is typically present, and hypoglycemia does not recur after adequate therapy.
Therapeutic principles
Since no direct antidote for oral antidiabetic drugs is available, the best treatment for metformin or glipizide intoxication is careful decontamination.
If metformin was ingested less than 2 hours ago, inducing emesis for decontamination is the method of choice. Activated charcoal should also be administered at a later time.
Otherwise, the therapy is symptomatic.
Special attention must be paid to cardiovascular function, kidney function, and water-electrolyte and acid-base balance.
Blood sugar should be optimized and monitored using appropriate infusion solutions, and lactate levels should also be monitored as a precaution. This applies particularly to metformin ingestion of >200 mg/kg body weight.
The use of lactate-containing infusion solutions should be avoided.
Gastrointestinal complaints should be treated.
Supplements
The treatment of antidiabetic drug poisoning requires a rapid and targeted approach. Therapy depends on the active ingredient, the amount ingested, the time of ingestion, and the animal’s clinical condition.
In cases of recent ingestion (less than 2–4 hours), decontamination is paramount:
- Inducing emesis using apomorphine (0.04 mg/kg IV or 0.08 mg/kg IM/SC in dogs) or xylazine (0.44 mg/kg IM in cats), provided the animal is conscious and neurologically stable
- Administration of activated charcoal (1–4 g/kg orally) to reduce further absorption
- For sulfonylureas, repeated administration of activated charcoal every 4–6 hours may be beneficial to interrupt the enterohepatic circulation
The main pillar of therapy for hypoglycemic patients is glucose supplementation:
- In conscious animals, initial oral glucose administration (honey, dextrose) can be performed
- In more severely affected animals, intravenous glucose administration is indicated: bolus with 0.5-1 mL/kg of a 50% glucose solution, followed by a continuous infusion with 2.5-5% glucose solution
- The infusion rate is adjusted based on regular blood sugar monitoring (every 1–2 hours), with the goal of maintaining blood sugar above 3.5 mmol/L (63 mg/dL)
- In sulfonylurea poisonings, hypoglycemia can persist for 24–72 hours, requiring a correspondingly long infusion therapy
Adjuvant therapeutic measures include:
- Glucagon (0.03-0.1 mg/kg IM or SC) can be used in severe hypoglycemia, but often has only a temporary effect
- Octreotide (1–5 μg/kg SC every 8–12 hours) can inhibit insulin release in sulfonylurea poisonings and is particularly indicated for therapy-resistant hypoglycemia
- Dexamethasone (0.1-0.2 mg/kg IV) can promote gluconeogenesis and reduce peripheral glucose utilization
In metformin poisonings, the treatment of lactic acidosis is paramount:
- Aggressive fluid therapy with isotonic saline solution
- Bicarbonate administration in severe metabolic acidosis (pH <7.1)
- Monitoring of kidney function and electrolytes
- In severe cases, hemodialysis or hemofiltration may be required
Intensive medical monitoring includes:
- Continuous or regular blood sugar measurements
- ECG monitoring in case of cardiovascular involvement
- Monitoring of body temperature and oxygen saturation
- Control of acid-base balance and electrolytes
In cases of seizures, anticonvulsive therapy with diazepam (0.5-1 mg/kg IV) or phenobarbital (2–4 mg/kg IV) is indicated.
Prognosis & follow-up care
The prognosis for antidiabetic drug poisonings largely depends on several factors: the specific drug class, the ingested dose, the time of treatment initiation, and the animal’s individual health status before poisoning.
With early detection and adequate therapy, the prognosis for most animals with antidiabetic drug poisonings is favorable. Metformin poisonings, in particular, have a good prognosis with timely treatment, as they rarely lead to severe hypoglycemia. Gastrointestinal symptoms usually subside within 24–48 hours.
Sulfonylurea poisonings may require a more cautious prognosis, as the hypoglycemic effect can last up to 72 hours. However, with adequate glucose supplementation and intensive monitoring, the prognosis is largely good here as well. The situation becomes critical if severe neurological symptoms such as persistent seizures or coma have already occurred before the start of therapy, as these can lead to irreversible brain damage.
The prognosis for metformin poisonings can be particularly unfavorable if severe lactic acidosis has already developed, especially in animals with pre-existing renal dysfunction. In such cases, the mortality rate is significantly higher.
Aftercare following antidiabetic drug poisoning includes:
- Regular monitoring of blood sugar levels after discharge from inpatient treatment, especially for poisonings with long-acting sulfonylureas
- Monitoring of kidney and liver function, especially after metformin poisonings
- Neurological follow-up examinations for animals that have experienced severe hypoglycemic episodes with neurological symptoms
- Nutritional management with small, frequent meals in the first few days after discharge
- Advising pet owners on preventive measures to avoid future poisoning incidents
Long-term consequences are rare with timely treatment. However, in severe cases, permanent neurological deficits can occur, especially if hypoglycemia has led to long-term cerebral ischemia. These can manifest as behavioral changes, learning deficits, or focal neurological deficits.
Research outlook
Research in the field of antidiabetic drug poisonings in small animals is continuously evolving. Current studies focus on several promising areas:
New antidotes and treatment strategies are the focus of research. While traditional therapies are primarily based on glucose substitution and decontamination, more specific approaches are being investigated. For sulfonylurea poisonings, studies show that octreotide can effectively inhibit insulin secretion. Current research evaluates optimal dosages and administration protocols for various animal species.
The development of point-of-care testing methods for the rapid detection of antidiabetic drugs in blood or urine could significantly accelerate diagnosis. Such tests would offer great clinical benefit, especially in cases with an unclear history.
Veterinary-specific toxicity profiles of newer antidiabetic drugs are being more intensively researched. With the introduction of new drug classes such as SGLT2 inhibitors or GLP-1 receptor agonists in human medicine, the risk of corresponding poisonings in pets also increases. Veterinary toxicological studies on these substances have been limited to date but are increasingly being conducted.
Long-term consequences of hypoglycemia-induced neurological damage and their management are also a focus of current research. Studies are investigating neuroprotective strategies that can be used during and after hypoglycemic episodes to minimize permanent brain damage.
The optimization of intensive medical monitoring through continuous glucose monitoring systems, as already established in human medicine, is being adapted for veterinary use. These systems could improve therapy management in severe poisoning cases and reduce the risk of recurrent hypoglycemic episodes during treatment.
Epidemiological studies on the incidence and risk factors of antidiabetic drug poisonings in pets provide important data for preventive measures. In particular, identifying particularly vulnerable populations (certain breeds, age groups, or behavioral types) could enable more targeted prevention strategies.
The development of safe storage systems for medications in households with pets is another area of research with practical relevance for the prevention of poisoning cases.
Frequently asked questions (FAQs)
- Which antidiabetic drugs are most dangerous for pets?
Sulfonylureas and insulins pose the highest risk, as they can cause severe and prolonged hypoglycemia. Even small amounts can be life-threatening for small dogs or cats. - How quickly do symptoms appear after antidiabetic drug ingestion?
Symptoms can appear at different speeds depending on the active ingredient. With insulins, first signs can be visible as early as 15–30 minutes, and with sulfonylureas typically within 1–2 hours. Metformin poisonings usually show gastrointestinal symptoms only after several hours. - Can my pet recover on its own if it has ingested antidiabetic drugs?
This is possible with very small amounts and certain active ingredients like metformin. However, with sulfonylureas or insulins, a severe, potentially life-threatening course is to be expected without veterinary treatment, as hypoglycemia is often persistent. - How long does my pet need to be monitored after antidiabetic drug poisoning?
The monitoring duration depends on the active ingredient. For metformin, 24 hours are often sufficient, while for sulfonylureas, monitoring for 48–72 hours may be necessary, as the hypoglycemic effect can be delayed and prolonged. - What immediate measures can I take if my pet has ingested antidiabetic drugs?
If the animal is conscious and ingestion was recent (less than 30 minutes ago), you can induce vomiting after consulting your veterinarian by phone. If symptoms are already present, you should seek veterinary attention immediately. For a conscious animal, you can rub honey or sugar water on its gums to temporarily raise blood sugar. - Can antidiabetic drug poisonings cause permanent damage?
Yes, especially severe and prolonged hypoglycemic states can lead to permanent neurological damage. The brain is particularly sensitive to glucose deficiency, and prolonged hypoglycemic phases can lead to irreversible brain damage. - Are certain animal breeds or species more susceptible to antidiabetic drug poisonings?
Small dog breeds and cats are particularly at risk due to their low body weight, as even small amounts can lead to toxic concentrations. Additionally, toy breeds and terriers often exhibit curious behavior, which increases the risk of ingestion. - How can I prevent antidiabetic drug poisonings in my pet?
Store medications in locked cabinets or containers inaccessible to animals. Do not take medications in the presence of your pets to minimize the risk of dropped tablets. Inform visitors who take antidiabetic drugs about the dangers to your pets. - Can I give my own antidiabetic drugs to my diabetic dog or cat?
No, human medications should never be administered without veterinary instruction. The dosage, pharmacokinetics, and tolerability differ significantly between humans and animals. Diabetic pets require therapy specifically tailored to them. - How much does the treatment for antidiabetic drug poisoning cost?
Costs can vary significantly depending on the severity of the poisoning and the required duration of treatment. Intensive medical care over several days with regular laboratory checks can cost between several hundred to over a thousand euros. Pet health insurance can be helpful in such cases.
Literature
- Heller, J. B. (2007). Metformin overdose in dogs and cats. VETERINARY MEDICINE-BONNER SPRINGS THEN EDWARDSVILLE-, 102(4), 231.
- Gwaltney-Brant, S. M. (2021). Antidiabetic drug toxicosis. In Veterinary Toxicology (pp. 515-522). Academic Press.
- Barrella, N., Eisenberg, B., & Simpson, S. N. (2017). Hypoglycemia and severe lactic acidosis in a dog following metformin exposure. Clinical Case Reports, 5(12), 2097-2103.
- Löwe G, Löwe O. Emergencies in Dogs and Cats – A Veterinary Guide. 2nd Edition. Kreuztal: Kynos-Verlag. 2021; 208 pp.