Vol. 23, No. 7 July 2001 633
Article #2 (1.5 contact hours)
Refereed Peer Review
■ Glipizide is the only antidiabetic
agent whose mechanism of
action is directed at the endocrine
■ Acarbose does not reverse any
in patients with diabetes. In fact,
the drug is not systemically
■ Of the oral antidiabetic drugs
available for cats, glipizide and
acarbose appear to have the
most efficacy and the least
potential for toxicity.
Drugs for Cats
University of Tennessee
Sara M. Cowan, DVM
North Carolina State University
Susan E. Bunch, DVM, PhD, DACVIM
Email comments/questions to
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,
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
■ 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
Closes ATP – K + channel
(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 were found to have the potential to
(C) Cell membrane
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
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
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
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
Compendium July 2001 Small Animal/Exotics 635
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
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
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
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
636 Small Animal/Exotics Compendium July 2001
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
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
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-
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.
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
Compendium July 2001 Small Animal/Exotics 637
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
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
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.,
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.
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.
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
638 Small Animal/Exotics Compendium July 2001
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
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.
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
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.
Compendium July 2001 Small Animal/Exotics 639
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
640 Small Animal/Exotics Compendium July 2001
will provide clues to the many unanswered questions
regarding glycemic control in cats.
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#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
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.
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.
5. All of the following are reported adverse effects of glipizide
therapy in cats except
e. high liver enzyme activity.
6. To which class of drugs does metformin belong?
a. α-glucosidase inhibitors
642 Small Animal/Exotics Compendium July 2001
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
b. increased stimulation of insulin secretion by the
c. enhanced number and activity of glucose transporters
d. increased uptake and oxidation of glucose in adipose
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
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
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.