Oral Antidiabetic Drugs for Cats - VetLearn.com

CE 

Vol. 23, No. 7 July 2001 633 

Article #2 (1.5 contact hours) 

Refereed Peer Review 

KEY FACTS 

■ Glipizide is the only antidiabetic 

agent whose mechanism of 

action is directed at the endocrine 

pancreas. 

■ Acarbose does not reverse any 

pathophysiologic derangements 

in patients with diabetes. In fact, 

the drug is not systemically 

absorbed. 

■ Of the oral antidiabetic drugs 

available for cats, glipizide and 

acarbose appear to have the 

most efficacy and the least 

potential for toxicity. 

Oral Antidiabetic 

Drugs for Cats 

University of Tennessee 

Sara M. Cowan, DVM 

North Carolina State University 

Susan E. Bunch, DVM, PhD, DACVIM 

Email comments/questions to 

compendium@medimedia.com 

or fax 800-556-3288 

ABSTRACT: Diabetes mellitus (DM) is commonly diagnosed in cats. In humans, treatment 

regimens for non–insulin-dependent DM include various combinations of dietary modification, 

exercise, insulin administration, and one or more oral antidiabetic drugs, which have been extensively 

evaluated in humans but not in cats. Glucose toxicity is a phenomenon of chronic hyperglycemia 

and must be understood before interpreting response to any antidiabetic therapy. 

This article provides a critical review of the oral antidiabetic drugs glipizide, metformin, troglitazone, 

and acarbose. 

Diabetes mellitus (DM) is a common endocrine disorder in cats. It is estimated 

to affect 1 in 300 cats, 1 with both forms of the disease defined by 

the ability of pancreatic beta cells to secrete insulin. 2 Type I DM is characterized 

by the destruction of insulin-producing beta cells in the islets of 

Langerhans. Type I DM is always insulin dependent; therefore, the treatment of 

choice is insulin. Type II DM is characterized by defects in glucose-stimulated 

insulin secretion by the pancreas and in peripheral tissue sensitivity to and use of 

insulin. 3–5 Initially, type II DM is non–insulin-dependent because of the ability 

of beta cells to produce some insulin. However, the progression of disease usually 

results in insulin dependence. 6 

In humans, treatment options for type II DM include various combinations 

of dietary modification, exercise, and administration of one or more oral antidiabetic 

drugs with or without insulin. The treatment options for type II DM in 

cats are not as diverse as those for humans for the following reasons: 

■ It is difficult to discern in cats whether DM is insulin dependent, and most 

cats are treated as insulin-dependent diabetics. 

■ Diabetic cats with finicky appetites may be difficult to manage with dietary 

changes. 

■ Oral antidiabetic drugs have not been extensively evaluated in cats. (Nevertheless, 

understanding their possible role in treating feline diabetics is important 

for veterinarians. Use of these drugs in cats may become more commonplace, 

and clients often have questions regarding their use.)

634 Small Animal/Exotics Compendium July 2001 

(A) Glipizide 

K + 

(B) 

K + 

K + 

K + 

K + 

Closes ATP – K + channel 

I 

(E) Exocytosis of vesicles 

Insulin leaves the pancreas to portal vein 

In general, oral antidiabetic drugs act by stimulating 

insulin secretion, decreasing hepatic gluconeogenesis, 

or improving muscle and adipose tissue sensitivity to 

insulin. Because type II DM is a progressive disease 7 

that ultimately requires insulin injections and/or multiple 

drug therapies, careful patient selection is essential 

for these drugs to be used successfully. 

Due to the high incidence of diabetes, diabetic complications, 

problems with long-term insulin use, and 

the hospital time and resources spent on managing diabetes 

in humans, 8 diabetologists have studied alternatives 

to insulin over the past 30 years. Similar investigations 

are needed in cats in light of the high euthanasia 

rate of diabetic cats (30% to 40%) and the knowledge 

gained in humans on the effects of diet, exercise, and 

antihyperglycemic drugs on glycemic control. 

The following factors are used to evaluate the efficacy 

of antidiabetic drugs 9–12 : 

■ The difference between pretreatment and posttreatment 

fasting blood glucose (FBG) and postprandial 

blood glucose (PPBG) concentrations 

■ Similar differences in glycosylated hemoglobin (Hb 

A 1c) or serum fructosamine concentrations 

■ Pretreatment factors serving as positive predictors of 

response to therapy 

■ Causes of failure to respond 

SULFONYLUREAS (GLIPIZIDE) 

Sulfonylureas were found to have the potential to 

K + 

(C) Cell membrane 

depolarization 

(D) 

Ca ++ 

Ca ++ 

Ca ++ 

Figure 1—Mechanism of action of glipizide at the pancreatic 

beta cell. Glipizide (A) binds to a receptor on the ATP– 

potassium (K + ) channel, which closes it, resulting in reduced 

potassium efflux from the cell. An increase in extracellular 

potassium (B) causes cell membrane depolarization 

(C) and calcium (Ca ++ ) influx (D). An increase in intracellular 

calcium is the direct stimulus for exocytosis of insulincontaining 

vesicles (E). 

I 

I 

treat diabetes over 50 years ago when researchers were 

studying their antibiotic effects. 9 Sulfonylureas are 

highly protein-bound derivatives of the sulfa antibiotics. 

Glipizide is a second-generation sulfonylurea; 

first-generation drugs of this class have less potency 

and higher polarity, are less lipid soluble, and have not 

been examined for use in cats. Sulfonylureas are well 

absorbed from the gastrointestinal (GI) tract. There 

are some weakly active or inactive metabolites produced 

in the liver. The liver and kidney clear sulfonylureas; 

hepatic inactivation is the primary route of 

clearance. 10 

The sulfonylureas are the only class of antihyperglycemic 

drug with a direct mechanism of action at the 

pancreatic beta cell. 11 The insulinotropic effect of sulfonylureas 

is depicted in Figure 1. 

Other effects of sulfonylureas have also been described. 

13 There is in vitro evidence for a decrease in 

hepatic gluconeogenesis, an increased number of insulin 

receptors in tissues of action, and increased 

postinsulin receptor activity. 12 

Efficacy 

Humans 

In humans with type II diabetes, glipizide decreases 

the FBG level by 60 to 70 mg/dl and the Hb A 1c by 

1.5% to 2%, 12 which is similar to the efficacy of insulin. 

7 In humans, factors that predict a positive response 

to sulfonylureas include diabetes diagnosed 

within the past 5 years, hyperglycemia in the range of 

220 to 240 mg/dl, adequate beta-cell function as measured 

by a high fasting C-peptide level, and no history 

of exogenous insulin treatment. 10,14 The likelihood of 

response to glipizide treatment is inversely correlated 

with the degree of blood glucose elevation at the start 

of therapy. 7 Therefore, carefully selecting patients with 

mildly to moderately elevated fasting and postprandial 

glucose levels for glipizide therapy is recommended and 

may improve efficacy. 

Failure of humans to respond to therapy as evidenced 

by an unacceptably minimal decrease in glucose 

concentrations after 3 months of therapy is related 

to patient factors (noncompliance, coexisting 

disease), drug factors (use of medications that antagonize 

insulin action or secretion, inadequate drug 

dosage), and disease progression. 12 A 6-year follow-up 

of humans treated with sulfonylureas showed that only 

5% (33 of 660) maintained normoglycemia. This attests 

to the nature of type II DM as a progressive disease 

and the eventual need for multidrug therapy, including 

insulin. 7

Compendium July 2001 Small Animal/Exotics 635 

Cats 

The data on efficacy of glipizide in cats is complicated 

by the uncertainty of the underlying diabetic state 

(type II versus type I DM) and the absence of blinded, 

placebo-controlled prospective clinical trials. The first 

study of glipizide in cats examined its effect on serum 

insulin and glucose concentrations in 10 healthy cats. 15 

Mean serum insulin concentration increased for 1 hour 

after glipizide administration, and mean serum glucose 

concentration decreased within 15 minutes of glipizide 

administration, with the lowest concentration at 60 

minutes and duration of effect up to 120 minutes. In a 

1993 study of 20 cats, Nelson and colleagues found improved 

clinical signs and blood glucose concentrations 

in 65% (13 of 20) of cats with DM that were treated 

with glipizide. 16a This included five cats that were considered 

complete responders based on resolution of 

clinical and laboratory indices of diabetes by the fourth 

week of therapy. Eight cats considered to be partial responders 

did have resolution of clinical signs but remained 

hyperglycemic (greater than 200 mg/dl) and 

glucosuric. 

In 1997, Feldman and coworkers monitored glycemic 

control in feline diabetics treated with only glipizide for 

50 weeks. 16b Glycemic control was achieved in 44% (22 

of 50) of cats. These cats were further classified as complete 

responders (14%), partial responders (12%), transient 

diabetics (12%), and transient responders (6%). 

However, three of these cats had long-term treatment 

failure, reducing the overall success rate to 38%. Results 

of long-term follow-up in a number of these diabetic 

cats supported the presence of type II DM and its progressive 

nature. The relationship between the degree and 

duration of hyperglycemia prior to therapy and the likelihood 

of response to glipizide in cats is unknown. Other 

predictive factors for determining response to therapy 

in cats are also unknown. Therefore, conservative patient 

selection promotes a better success rate when using 

glipizide in cats. Guidelines for patient selection as well 

as therapeutic protocols have been described. 10,17–19 

Side Effects 

Humans 

In humans, adverse effects of sulfonylureas are typically 

mild and reversible upon discontinuation of drug 

administration. The most important side effect of therapy 

is hypoglycemia, which is estimated to occur in 2% 

to 4% of humans treated for type II DM with a sulfonylurea. 

For comparison, the incidence of hypoglycemia 

due to insulin therapy is the same. 12 Other 

common side effects include cutaneous rashes and GI 

disturbance, while less common side effects include 

mild thrombocytopenia, mild hemolytic anemia, and 

high liver enzyme activity. 20 

Risk factors that predispose humans to adverse effects 

include decreased glomerular filtration rate, hepatic 

insufficiency, mild DM (mean serum glucose concentration 

of 140 mg/dl), and the simultaneous use of 

drugs that interact with the pharmacokinetics of sulfonylureas 

(e.g., aspirin, trimethoprim, H 2-blockers, 

warfarin, β-adrenergic blockers, sympatholytic drugs, 

thiazides, loop diuretics, corticosteroids). 12,20–22 


The incidence of side effects due to glipizide in cats 

was 16% in 50 cats treated for 50 weeks. 16 Commonly 

reported side effects are high liver enzyme activity, hepatotoxicity, 

anorexia, and vomiting, all of which may 

resolve with temporary discontinuation of the drug. 

Liver enzyme activity may return to normal despite 

continued administration of glipizide, suggesting that 

elevated liver enzyme activity may be seen with or 

without underlying hepatotoxicity. GI side effects resolve 

or improve by administering the drug with food. 

Based on current information, the incidence of hypoglycemia 

(usually asymptomatic) ranges between 12% 

to 15%. 7,16b The incidence of mild hypoglycemia may 

be underestimated due to the subtle clinical signs associated 

with its occurrence. 10 

BIGUANIDES (METFORMIN) 

Metformin is a biguanide antihyperglycemic agent. 

The active component, guanidine, is found naturally in 

animal and plant material and explains the medieval 

European practice of administering components of the 

French lilac flower (Galega officinalis) to diabetic patients. 

23 Unlike glipizide, it is not highly protein bound 

or metabolized. To date, there are two reports of metformin 

pharmacokinetics in cats. The mean oral 

bioavailability in six healthy adult cats was found to be 

48%. 24 The peak plasma concentration occurs between 

1 and 3 hours after oral administration. 24,25 Ninety percent 

of the drug is excreted in the urine within 12 

hours of administration. 26 

Because metformin improves insulin sensitivity in peripheral 

tissues, it is not effective in the absence of insulin. 

27 Whereas glipizide results in an increase in 

serum insulin concentration to lower blood glucose, 

metformin results in a decrease in serum insulin concentration. 

In humans and rats, therapeutic concentrations of 

metformin in the liver result in improved insulin-induced 

suppression of hepatic gluconeogenesis, which 

correlates with decreases in FBG concentrations. 12,26


Also, glucagon-induced gluconeogenesis is reduced. In 

myocytes, metformin increases the activity of the insulin 

receptor tyrosine kinase and enhances the number 

and activity of the glucose-transporter-4. Uptake of 

glucose by muscle, muscle glycogen formation, and 

glucose oxidation are all increased. 28 In adipose tissue, 

metformin increases the uptake and oxidation of glucose 

and increases the binding of insulin to its receptors. 

26 The antilipolytic action of insulin is thereby reduced, 

causing weight loss even when diet and exercise 

are held constant. 27 This benefit in obese patients is in 

contrast to insulin and glipizide therapy, which increases 

insulin concentrations. 28 Metformin has no effect 

on insulin production or secretion at the pancreatic 

beta cell. 

Efficacy 

Humans 

When used as monotherapy in humans, the FBG level 

decreases by a mean of 60 to 70 mg/dl and the Hb 

A 1c concentration by a mean of 3%. 7,12,24,26–30 When 

compared with other therapies (insulin, glipizide), metformin 

causes a greater decrease in the PPBG concentration 

compared with the FBG concentration. 

When used in combination therapy with a sulfonylurea 

in humans, the FBG decreases by 63 mg/dl more 

than with sulfonylurea alone. 7,31 When patients with 

poorly controlled type II DM on insulin were treated 

with metformin, Hb A 1c concentrations were significantly 

lower compared with placebo and there was improved 

glycemic control with the use of 30% less insulin. 

10,30 This indicates that the hypoglycemic effect of 

metformin is additive to that of sulfonylureas and insulin 

in humans, a concept that has not been studied in 

cats. 

Primary treatment failure, defined as failure to 

achieve glycemic control at the onset of therapy, occurs 

at an overall incidence of 12% in humans. 7,10 As with 

most patients, the incidence of secondary treatment 

failure (failure to maintain target glycemic levels after 

an initial positive response) with metformin increases 

with duration of therapy because of the progressive nature 

of type II DM. 


Recently, 25 five newly diagnosed diabetic cats and one 

acromegalic diabetic cat that was on insulin therapy 

were given metformin (10 mg sid to 50 mg bid PO). 

Clinical signs, blood glucose, serum fructosamine, and 

Hb A 1c values did not improve after 7 weeks in three 

cats. There was no improvement in the cat with diabetes 

and acromegaly. One cat developed ketoacidosis, and 

one was found dead (cause unknown) 2 weeks after ini- 

BOX 1 

Chronic Hyperglycemia: A Brief Review 

Chronic hyperglycemia causes pancreatic beta cells 

to be desensitized to glucose, resulting in impaired 

insulin secretion. In addition, there is relative insulin 

resistance in peripheral tissues. Insulin receptors can 

move beneath the cell membrane as a result of chronic 

hyperglycemia, and the glucose transport systems 

become dysfunctional. 4 The end result is a low serum 

insulin concentration with hyperglycemia (this is in 

contrast to insulin resistance, characterized by a 

very high insulin concentration accompanying 

hyperglycemia). Glucose-induced desensitization 

of the pancreas and peripheral tissues is reversible. 

Glucose toxicity is the term used for an irreversible 

state of beta-cell dysfunction and resembles type I 

DM because the pancreas becomes unresponsive after 

stimulation by insulin secretagogues despite its ability 

to produce insulin. Therefore, results of insulin 

secretory tests to distinguish type I from type II DM 

in cats are inconsistent partly because of the effects of 

glucose-induced desensitization and glucose toxicity. 3 

A clinically useful way of distinguishing type I from 

type II DM in cats may be to evaluate response to 

treatment with antidiabetic drugs. 

tiating metformin administration. One cat achieved improved 

glycemic control for 5 months and then developed 

acute pancreatitis and loss of glycemic control. 

There are no other published data on the efficacy of 

metformin in cats. It has been speculated that many cats 

suffer from glucose toxicity as a result of chronic hyperglycemia 

(Box 1); therefore, improving insulin sensitivity 

in peripheral tissues by using metformin may provide 

little benefit in cats with glucose toxicity. 

Side Effects 

Humans 

The overall incidence of adverse effects of metformin 

treatment in humans is 20% to 30%. The most common 

effects are diarrhea, nausea, abdominal pain, and a 

metallic taste. 28 Side effects can be minimized by taking 

metformin with food and by slowly increasing the dose 

in small increments once therapy is initiated. 10,27 

Hypoglycemia is a rare occurrence in humans treated 

with metformin alone because the drug does not increase 

insulin secretion. An uncommon yet potentially 

fatal adverse effect of metformin therapy documented 

in humans is lactic acidosis, with an estimated incidence 

of 0.027 to 0.06 cases per 1000 patient-years. 12,28 

Metformin precipitates lactic acidosis by promoting the


conversion of ingested carbohydrate to lactate by the 

intestinal mucosa, which is subsequently absorbed and 

metabolized by the liver. 10 Incriminating metformin as 

the sole cause of all lactate elevations is complicated because 

obesity and diabetes also slightly raise blood lactate 

concentrations. 26 

In most patients suffering from metformin-associated 

lactic acidosis, predisposing factors include concurrent 

renal insufficiency, liver disease, or other major illness 

causing tissue hypoperfusion or hypoxia. 10,12,26 The 

risk of death from metformin-induced lactic acidosis 

(50%) is similar to that of severe hypoglycemia in sulfonylurea-treated 

patients. 26 

There are infrequent reports of drug interactions 

with metformin. In humans, cimetidine causes an elevation 

of plasma metformin by competition for renal 

tubular secretion. 28 


There is little information on the adverse effects of 

metformin in cats. In cats, the drug appears to be excreted 

primarily by glomerular filtration. 24 The effects 

of cimetidine on plasma metformin concentration in 

cats are unknown. 

In one study, six healthy male cats received metformin 

(25 mg sid for 7 days, then 25 mg bid for 14 

days) and two cats received placebo. All six cats receiving 

metformin, but neither cat receiving the placebo, 

developed a combination of inappetence, weight loss, 

and/or intermittent vomiting. 25 In another study, six 

healthy adult cats were given 25 mg metformin IV and 

PO. There was no mention of adverse effects (e.g., 

vomiting). 24 

THIAZOLIDINEDIONES (TROGLITAZONE) 

Thiazolidinediones were discovered by Japanese scientists 

almost 2 decades ago as they were studying compounds 

to serve as hypolipidemic drugs. 32 One analogue, 

troglitazone, was approved for human use by the 

FDA in 1997. Troglitazone is rapidly absorbed (its 

bioavailability is 40% to 50%), and food increases the 

absorption. 33 In humans, troglitazone undergoes 

metabolism by sulfation, glucuronidation, and oxidation 

into active conjugates. Hepatic impairment causes 

plasma concentrations of troglitazone to increase. 33 Despite 

proven efficacy, its suitability as a first-line drug to 

treat type II DM has been questioned because of the 

risk of severe liver dysfunction. 34,35 

Like metformin, troglitazone enhances peripheral insulin 

sensitivity and thereby lowers both glucose and 

insulin levels. Troglitazone reduces the expression of 

specific genes responsible for producing the regulatory 

enzymes of hepatic gluconeogenesis, thereby slowing 

the rate of hepatic gluconeogenesis. 36 In muscle and fat, 

thiazolidinediones cause an increase in intracellular glucose 

transport, which increases glucose metabolism and 

decreases peripheral demand for insulin. 10,12,37 Troglitazone 

has no effect on insulin production or secretion at 

the pancreatic beta cell. 

Efficacy 

Humans 

Clinical trials show that troglitazone achieves longterm 

(up to 2 years) glycemic control in humans. 32,33,35,37 

To date, six trials examining troglitazone as the sole 

agent for treating type II DM showed a mean decrease 

in FBG of 34 mg/dl and in Hb A 1c of 0.6%. 12 Therefore, 

troglitazone is not as efficacious as monotherapy 

when compared with other classes of antidiabetic drugs. 

Primary treatment failure occurs in 25% of humans 

with type II DM treated with troglitazone alone. 12,35 

Troglitazone is more effective in patients with the syndrome 

of insulin resistance, where serum insulin concentrations 

are very high. This is in keeping with the 

described mechanism of action in peripheral tissues 

(enhancing insulin sensitivity). Combination therapy 

with metformin is not recommended because troglitazone 

and metformin have similar mechanisms of action 

and do not show complementary effects as do metformin 

and a sulfonylurea or troglitazone and a sulfonylurea. 


There is no published information on the efficacy of 

troglitazone in cats. 

Side Effects 

Humans 

Troglitazone-related adverse effects occurred in one 

fourth of patients using troglitazone either as monotherapy 

or in combination with a sulfonylurea. 34,35–38 

Liver-related death occurs in 1 of 100,000 humans. 35 

This has raised questions regarding the role of troglitazone 

in the repertoire of antidiabetic drugs; therefore, 

troglitazone is no longer recommended by the FDA as 

monotherapy. 12 The causative mechanism of hepatotoxicity 

is unknown but may represent idiosyncratic injury 

as a result of aberrant metabolism, resulting in the accumulation 

of hepatotoxic metabolites. 39 

Troglitazone may cause expansion of the plasma volume; 

5% of patients receiving the drug experience edema. 

Its use is contraindicated in patients with New 

York Heart Association class III or IV cardiac status. 12,38



There are no published data on adverse effects of 

troglitazone in cats. 

α-GLUCOSIDASE INHIBITORS (ACARBOSE) 

α-Glucosidase inhibitors delay glucose absorption 

from the GI tract. Acarbose, an α-glucosidase inhibitor, 

is an oligosaccharide extracted from the bacterium 

Actinomyces. It was first developed as a starch blocker 

for obesity. Acarbose was introduced in the United 

States in 1995 and has recently been studied for use in 

domestic animals. 40,41 

Dietary control of blood glucose through stringent 

dietary regimens has been the proposed foundation of 

early therapy for human diabetes, but noncompliance 

with eating small, frequent meals is high. 7,10 Similarly, 

owners of diabetic cats are often unable to provide 

small, frequent meals. Appropriate dietary therapy for 

diabetic cats is outlined elsewhere. 19 

Acarbose inhibits the α-glucosidases, which include 

enzymes produced in the brush border of the small intestine. 

Sucrase, maltase, isomaltase, glucoamylase, lactase, 

and others function to digest oligosaccharides and 

disaccharides (complex carbohydrates) into monosaccharides 

(glucose), which are subsequently absorbed 

through the small intestine. 42 Acarbose competitively 

and reversibly inhibits these enzymes, delaying the hydrolysis 

of complex carbohydrates without affecting the 

absorption of the glucose molecule. 10 Carbohydrate absorption 

then shifts to more distal parts of the intestines. 

43 Carbohydrates that reach the large intestine 

are metabolized by colonic bacteria into fatty acids for 

absorption. 

Acarbose does not cause a malabsorptive state; rather, 

it slows the digestive and absorptive processes. The end 

result is a blunted entry of glucose into the systemic 

circulation, thus reaching the pancreatic beta cell at 

lower blood concentrations. 44,45 Acarbose does not decrease 

hepatic glucose output or reverse any pathophysiologic 

derangements in patients with diabetes. In fact, 

the drug is not systemically absorbed. 

Efficacy 

Humans 

Human studies with acarbose have documented a 

decrease in PPBG concentrations and glucosuria for 

up to 3 years irrespective of concomitant therapy. 

10,42,44–48 This occurs in both insulin- and non–insulin-dependent 

DM, which may have implications 

for veterinary medicine because discriminating between 

type I and type II DM would not be a factor in 

deciding whether or when to prescribe the drug. When 

used alone in humans, acarbose decreased the FBG 

level by only 25 to 30 mg/dl, the PPBG level by 40 to 

50 mg/dl, and the Hb A 1c concentration by 0.5% to 

1.2%. 49–51 Although less potent than insulin, glipizide, 

or metformin, acarbose is prescribed as initial and adjunctive 

therapy in obese patients. Acarbose does not 

affect the absorption of other antidiabetic drugs. It is 

not recommended for patients with normal or decreased 

body condition. 50 


The efficacy of acarbose in cats is not established. Because 

acarbose works by interfering with starch digestion 

and absorption, its effectiveness needs to be studied 

in cats in light of their low carbohydrate intake 

when compared with humans. 12 Recently, seven obese 

diabetic cats (five on insulin therapy) were evaluated for 

the effects of acarbose (12.5 mg PO bid with meals) 

and a high-protein diet on glycemic control. Insulin administration 

was discontinued in four of five cats during 

the course of the 4-month study. Improved serum 

fructosamine and FBG concentrations as well as improved 

attitude compared with pretreatment values 

were noted in six cats. 41 

Side Effects 

Humans/Dogs 

Up to 30% of humans experience mild and transient 

GI side effects from acarbose that diminish despite continued 

drug use. Bloating with abdominal discomfort, 

flatulence, and diarrhea have been reported. 45,52–55 In 

five healthy dogs fed a high-fiber diet and given 200 

mg acarbose daily, four dogs developed soft to watery 

stools and two dogs lost weight during the study. 40 

To minimize the incidence of GI side effects, acarbose 

therapy should be initiated with a low dose and 

gradually increased to reach the minimally effective 

dose. 48 Food must be present in the bowel with acarbose 

for the drug to have its effect, but side effects may 

occur regardless of the presence or absence of food. 

Other adverse effects are dose dependent and include 

high liver enzyme activities and abnormal results of liver 

function tests. These abnormalities resolve when the 

drug is discontinued. Hypoglycemia does not occur as a 

direct result of acarbose therapy. However, if hypoglycemia 

occurs due to concurrent administration of 

other antidiabetic drugs (insulin, glipizide), pure glucose 

should be ingested. 52–55 


The appropriate dose for cats has not been established.


CONCLUSION 

The mechanism of action, efficacy, and side effects of 

the oral antidiabetic drugs glipizide, metformin, troglitazone, 

and acarbose have been extensively studied in 

humans but not in cats. On the basis of limited data, 

glipizide and acarbose appear to have the most efficacy 

and the least potential for toxicity when compared with 

metformin and troglitazone. Careful patient selection is 

important. Oral antidiabetic drugs may be appropriate 

for cats that are in good overall health with early or 

mild clinical signs of diabetes and those with owners 

who are unwilling or unable to administer insulin injections. 

There are complications 56 and many uncertainties 

regarding the current use of oral antidiabetic 

agents in cats. They should not be used in cats with evidence 

of diabetic complications (e.g., ketoacidosis, infection, 

any concurrent disease). 

Although the difficulty in differentiating between 

type I and II DM in cats complicates the ideal treatment 

plan for each patient, it is clear that not every 

newly diagnosed diabetic cat requires exogenous insulin. 

Hyperglycemia in cats with type II DM may be a 

reflection of impaired insulin secretion from the pancreas, 

increased hepatic glucose output, decreased peripheral 

insulin sensitivity, and intestinal glucose ab- 

sorption. If so, therapy would ideally revolve around 

correcting these abnormalities by the use of dietary 

changes, oral antidiabetic agents, insulin, or a combination 

of these treatments. 4,10,12,18,32,57–59 

Some cats that are exquisitely sensitive to insulin may 

benefit from a diet change and the use of an oral agent 

without insulin. Other cats that are well maintained 

with insulin and then become unregulated may represent 

the progressive nature of type II diabetes; these cats 

may also benefit from the addition of drugs (e.g., glipizide 

or acarbose alone or with insulin). More information 

is needed on the use of combination therapy in 

cats and the efficacy and/or toxicity of metformin and 

troglitazone. Initial observations have not been encouraging. 

The reason for the apparent lack of efficacy compared 

with that in humans remains unknown but may 

be related to low serum insulin concentrations associated 

with glucose toxicity. 

Improving recognition of type II DM in cats and further 

study of oral antidiabetic agents are important for 

managing the unique characteristics of feline diabetes. 

To date, clinical trial data are insufficient in both human 

and veterinary medicine for determining the optimal 

insulin formulation and optimal combinations and 

dosages of oral agents. 59 We hope that future research


will provide clues to the many unanswered questions 

regarding glycemic control in cats. 

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ARTICLE 

CE 

#2 CE TEST 

The article you have read qualifies for 1.5 contact 

hours of Continuing Education Credit from 

the Auburn University College of Veterinary 

Medicine. Choose the best answer to each of the fol- 

lowing questions; then mark your answers on the 

postage-paid envelope inserted in Compendium. 

1. Which of the following is not a result of glucose toxicity? 

a. desensitization of the pancreatic beta cell to glucose 

b. dysfunctional glucose transport systems in peripheral 

tissues 

c. movement of peripheral insulin receptors beneath 

the cell membrane 

d. low serum insulin concentration 

e. depletion of liver glycogen stores 

2. Insulin resistance is characterized by _____ serum insulin 

concentration and _____ blood glucose. 

a. high; low 

b. high; high 

c. low; high 

d. low; normal 

e. low; low 

3. The direct physiologic stimulus for insulin secretion 

by the pancreatic beta cell is 

a. closing of the ATP–potassium channel. 

b. hypoglycemia. 

c. intracellular calcium influx. 

d. intracellular potassium influx. 

e. opening of the ATP–potassium channel. 

4. In humans, the likelihood of response to glipizide is 

improved by selecting patients with 

a. mild to moderate hyperglycemia. 

b. marked hyperglycemia. 

c. insulin resistance. 

d. a history of ketoacidosis. 

e. ketonuria. 

5. All of the following are reported adverse effects of glipizide 

therapy in cats except 

a. jaundice. 

b. vomiting. 

c. hypoglycemia. 

d. constipation. 

e. high liver enzyme activity. 

6. To which class of drugs does metformin belong? 

a. α-glucosidase inhibitors 

b. biguanides


c. sulfonylureas 

d. thiazolidinediones 

e. glycosylated proteins 

7. Which of the following are mechanisms by which 

metformin lowers the blood glucose concentration? 

a. improved insulin-induced suppression of hepatic 

gluconeogenesis 

b. increased stimulation of insulin secretion by the 

pancreas 

c. enhanced number and activity of glucose transporters 

into myocytes 

d. increased uptake and oxidation of glucose in adipose 

tissue 

e. a, c, and d 

8. Troglitazone is not commonly used in cats because 

a. clinical trials have shown that it does not lower 

blood glucose concentrations in cats as it does in 

humans. 

b. it causes profound hypoglycemia in cats. 

c. it causes renal toxicity in cats. 

d. its efficacy and toxicity in cats is unknown. 

e. it cannot be used concomitantly with insulin. 

9. In a study of seven obese diabetic cats evaluated for the 

effects of acarbose, 

a. insulin administration could not be discontinued in 

any of the cats due to refractory hyperglycemia during 

acarbose administration. 

b. the cats did not tolerate acarbose administration 

due to the metallic taste reported in humans. 

c. serum fructosamine and FBG concentrations were 

improved compared with pretreatment values in 

most of the cats. 

d. the drug resulted in complete resolution of clinical 

signs of DM in all seven cats. 

e. long-term follow up on all seven cats showed 

glycemic control on acarbose alone after 1 year. 

10. Which of the following statements regarding acarbose 

administration is true? 

a. Acarbose must be taken on an empty stomach in 

order to have an affect. 

b. Compared with glipizide, metformin, and troglitazone, 

acarbose has the most profound effect in lowering 

the blood glucose concentration. 

c. The use of acarbose is not suitable for insulin-dependent 

DM (type I). 

d. Therapeutic serum concentrations of acarbose are 

met by tid administration. 

e. GI side effects in humans are usually transient and 

diminish despite continued use.

Oral Antidiabetic Drugs for Cats - VetLearn.com

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