INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 24
NEWER ANTIDIABETIC DRUGS
A. Sundaram* , C. R. Anand Moses*, S. Ilango*, V. Seshiah**
INTRODUCTION
The basic defects in Type 2 diabetes consist of (1)
Insulin deficiency (2) Insulin resistance and (3)
increased hepatic glucose production (HGP) leading
to glucotoxicity, beta cell exhaustion and finally
beta cell failure. The treatment strategies to
overcome these defects are:
1) Modified meal Plan
2) Exercise
3) Blood glucose lowering drugs and
4) Insulin
The current oral blood glucose lowering agents and
dietary measures only partially correct the multiple
metabolic defects in NIDDM with insulin resistance
remaining relatively impervious to treatment
Hypoglycaemia and secondary failure are common
with presently available sulphonylureas and hence
the need for newer blood glucose lowering drugs. In
case of NIDDM, a successful new drug should
correct atleast one of the major underlying
metabolic disturbances. i.e. reduce insulin
resistance, enhance insulin production and secretion
in response to glucose, suppress exessive hepatic
glucose production or improve glucose uptake and
utilisation in peripheral tissues particularly, skeletal
muscle. Within the last few years three new groups
of drugs have been identified and they are:
a) Alpha glucosidase inhibitors, eg. Acarbose
b) Insulin Sensitizer, eg. Troglitazone.
c) Insulin secretoguogues, eg. Glimepiride and
Repaglinide
The following review will discuss each of these
groups of drugs in detail.
ALPHA-GLUCOSIDASE INHIBITORS
In human salivary amylase, pancreatic amylase and
alpha-glucosidase are the enzymes involved in the
digestion of starch. All complex carbohydrates like
starch and sucrose have to be converted to simple
carbohydrates in the small intestine by an enzyme
alpha-glucosidase before absorption. Drugs which
inhibit the action of alpha-glucosidase known as
glucosidase inhibitor, preventing the breakdown of
complex carbohydrates thereby delay or preventing
carbohydrate absorption. Glucosidase inhibitors are
three types:
1. Reversible competitive inhibitors of alphaglucosidase.
eg: a. Acarbose; b. Meglital
2. Irreversible glucosidase inhibitor eg:
Gasternospermine.
3. Powerful Sucrose inhibitor eg: Veglibose.
Acarbose is freely available for clinical use. Other
drugs are under clinical trial.
Acarbose
Acarbose is a psuedotetrasaccharide and is a
reversible competitive inhibitor of the brush border
alpha glucosidases (mainly glucoamylase, sucrose
and maltose) as well as alpha amylase. Acarbose
binds to alpha-glucosidase with high affinity.
Mode of Action:
1. Acarbose blocks the digestion of starch, sucrose
and maltose. The digestion of carbohydrate is
delayed and occurs throughout the small
intestine, rather than upper part of jejunum.
Absorption of glucose and other
monosaccharides in not affected. The net result
is a decrease in post prandial rise in blood
glucose. Most of the carbohydrate is eventually
absorbed and that which is now absorbed is
metabolised by the bacteria in the colon to short
chain fatty acids which are then absorbed in the
colon.
2. Acarbose decreases meal stimulated secretion of
gastric inhibitory polypeptide and other
gastrointenstinal peptide (inhibitors) hormones.
There is smaller increase in post prandial blood
sugar level that leads to smaller increase in
insulin level.
3. Acarbose does not cause weight gain with the
therapeutic doses.
* Dr. Ambedkar Institute of Diabetes, Govt. Kilpauk Medical College & Hospital Chennai-600 010.
** Chief Diabetologist, Apollo Hospitals, Chennai-600 006.
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 25
Side Effects:
Abdominal fullness, borborygmi, increased
intestinal flatulence and diarrhoea are major side
effects of alpha-glucosidase inhibitors. These side
effects are due to undigested sugars passing through
large bowel where bacterial fermentation occurs,
producing both carbondioxide and large quantities
of osmotically active glucose load, leading to
diarrhoea and flatulence. These symptoms occur in
the first few weeks of treatment and abate with
continued long term treatment.
Degradation of Acarbose :
Mostly occurs in the intestine. Some of the
degradation products and the trivial amount of the
parent drug enter systemic circulation and are
excreted in urine. When high doses of Acarbose is
used, liver enzymes level should be checked.
Concomitant use of antacids, bile acid resins,
intestinal absorbents, or digestive enzyme
preparations may interfere with the effectiveness of
acarbose and should be used with care.
Contraindications to Acarbose use are primary
therapy for Type 1 diabetes, significant
gastrointestinal disorders and pregnancy or
lactation.
Acarbose is administered orally three times a day
and chewed with the first mouthful of food. Initial
dose is 50 mg. Three times a day. Two weeks later
the dose is increased to 100 mg, thrice daily and
thereafter at 4 weeks interval, the dose is increased
upto 200 mg. Thrice daily or until the required
glycaemic control is achieved.
Uses :
In non-diabetics and in Type 2 diabetics acarbose
produces a dose related decrease in post-prandial
hyperglycaemia. Acarbose theraphy causes a
corresponding reduction in post prandial plasma
insulin response. Long term treatment either as
monotheraphy or in combination with S.U, acarbose
improves basal blood sugar concentration as well.
Thus insulin resistance decreases and sensitivity
improves consequent to reduction in
hyperglycaemia.
1. Primary Therapy:
When FBS is less than 11.1 mmol, acarbose is
said to decrease FBS by 1 mmol,
PPBS by 3 mmol and HbA1c by 1% Acarbose
does not cause hypoglycaemia when used as
primary therapy.
2. As an adjuvant to:
Sulphonylurea, b. Metformin and c. Insulin in
Type 2 DM. A reduction in the dosage of these
drugs occur when Acarbose is used as an
adjuvant.
3. Acarbose decrease serum TGL in patients with
hypertriglycidemia by decreasing VLDL
synthesis.
4. Acarbose in impaired glucose tolerance:
Acarbose has been tried in persons with IGT for
prevention and postponment of onset of Type 2
Diabetes.
5. In IDDM:
Long term treatment with acarbose reduces both
post prandial and basal hyperglycaemia and
reduces insulin requirement by 10 to 30 %
interestingly, episodes of hypoglycaemia
between meals may be less frequent and less
severe in IDDM.
In treatment of hypoglycemia in patients taking
acarbose, only oral or IV (glucose) should be given.
Sucrose and other complex carbohydrates should
not be used.
For Further Reading:
1. Rebovitz H. Oral hypoglycemic agents. In: Joslin’s
Diabetes Mellitus. Eds. Kahn and Weititr GC, Lea and
Febiger, Philadelphia, 1994; 521-2.
2. Bailey CJ, Williams G, Pickup J. New drugs in the
management of diabetes and its complications. Text book
of diabetes, Eds Pickup J and williams G. Blackwell,
London 1997; 84.5 – 6.
3. Jean-Louis Chaisson et al. The efficacy of Acarbose in the
treatment of patients with NIDDM – Annals of Internal
medicien 1994’ 928-35.
4. Marlkolf Hanefeld et al. Therapeutic Potentials of
Acarbose as a first line drug in NIDDM subjects
insufficiently treated with diet alone. Diabetes Care. 1991;
14:732-7.
5. Sat Hit Vanasaeng et al. Effects of Alpha-glucosidase
inhibitor(acarbose) combined with sulphonylurea or
Sulphonylurea and metfermin in treatment of NIDDM. J.
Med Asse, Thai 1995; 18: 578-84.
6. Caniff RF, Shapire JA et al, Reduction of Glycosylated
haemoglobin and post prandial hyperglycaemia by
Acarbose in patients with NIDDM. Diabetes Care, 1995;
18: 817-24.
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 26
INSULIN SENSITIZERS
Insulin deficiency, insulin resistance and increased
hepatic glucose output are the hallmark of
pathogenesis of Type 2 diabetes. Sulphonylureas
increase insulin secretion and may improve insulin
sensitivity while the biguanide metformin improves
insulin action. One of the exciting areas in the
management of Type 2 diabetes is the development
of pathogentically targetted drugs to overcome
insulin resistance, namely the thiozolidinediones.
They work mainly by reducing peripheral insulin
resistance in adipocytes, skeletal muscles and to a
lesser extent by decreasing hepatic glucose
production. These drugs facilitate insulin action in
liver, muscles and adipose tissue. They do not
stimulate insulin secretion. Pioglitazone, englitazone
and troglitazone are the thiozolidine derivatives.
Only Troglitazone is in clinical use. Troglitazone
was developed in 1980 and was synthesized later
with an alpha-tocopheral substitution and has antioxidant
properties in addition to improving insulin
sensitivity.
Mechanism of Action of Troglitazone:
In Adipose Tissue :
1. Thiozolidinediones increase glucose oxidation,
lipogenesis and increase the expression of
GLUT-4, the glucose transporters in adipose
tissues.
2. Recently these drugs are found to interact or
bind with the PPAR-Y (Peroxidase Proliferator
Activated receptor –Y) nuclear receptor of
adipocytes. PPAR – Y is the binding site for
troglitazone and this leads to differentiation of
insulin resistant large size adipocytes, into
insulin sensitive small adipocytes, without
increasing adipocyte mass and thereby reducing
insulin resistance and improving insulin
sensitivity. Other suggested mechanism of
actions are:
a. by reducing white adipose tissue mass and
increasing brown adipose tissue mass.
b. by decreased production of TNF alpha,
leptin, and FFA levels in adipose tissue, all
of which cause insulin resistance.
3. In Muscle:
Troglitazone [1] increases GLUT-4 and
increases the activity of glycogen synthase.
There is increased glyucogenesis and glycolysis.
4. In Liver:
Thiozolidinediones reduce hepatic glucose
production by suppressing neoglucognesis. This
is by restoring the ability of insulin to suppress
the expression in the liver of PEPK
(phosphoenolpyruvate carboxykinase) the rate
limiting enzymes of gluconeogenesis.
5. Thiozolidinediones have been suggested to
decrease hyperglycaemia in activating
protoinkinase which reduces kinase activity of
insulin receptor.
6. Troglitazone reduces triglyceride level and
NEFA. It also decreases cholesterol, increases
HDL and to a lesser extent increases LDL level.
7. Troglitazone has no effect on body weight.
Safety data and Adverse Events:
Were reported from 30 clinical trials and 74000
weekly patient exposur to Troglitazone.
a. No hypolglycaemia occurs with Troglitazone
when used alone.
b. 2 to 3 % reduction in haemoglobin level with 5
to 7% elevation in plasma volume have been
reported. Hb% level did not fall outside the
normal range.
c. Liver Enzyme Activity increased to more than
3 fold of normal in some patients on
Troglitazone treatment. Varying degrees of liver
damage have been received by US, FDA. This
include irreversible damage and death in one.
This is probably an idiosynerotic reaction.
Prescribing Information
Troglitazone is metabolised by the liver and
excreted into the bile. The presence of renal
insufficiency does not effect the serum level or
metabolism of the drug.
1. In Type 2 diabetics, this is accompanied by
concomitant reduction in both fasting and post
prandial insulin levels. There will be significant
reduction in triglyceride level and an increase in
HDL cholesterol level. Dosage is 200-600
mg/day average dosage is 400 mg/day. Dosage
is once per day with breakfast and tiration is not
necessary.Troglitazone may be started either as
monotherohy or in combination with
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 27
sulphonylureas, acarbose, metformin and with
insulin.
2. In poorly controlled Type 2 diabetics on insulin
therapy, the insulin dosage reduction is not
recommended at the outset. Along with insulin,
troglitazone therapy is started. Once fasting
blood sugar falls to 120-140 mg a reduction of
10 to 20% of insulin dose is recommended in
order to aviod hypoglycaemia. Some studies
have reported (I) a reduction of insulin dosage
upyo 58%, (ii) reduction of insulin injection
from three to one per day in 40% of diabetics
treated with Troglitazone and (iii)
discontinuation of insulin in 10% of diabetics.
3. Troglitazone is the ideal drug for syndrome X
and other insulin resistant states.
4. In IGT :
In patients with IGT, Troglitazone decreases
insulin resistance and improves insulin
sensitivity,. It reduces insulin level and
normalises blood glucose level and prevents or
postpnes onset of Type 2 DM.
5. In Women with Polycstic Ovary Syndrome
with IGT :
Trogilazone improves glucose tolerance ,
insulin sensitivity and causes a fall in androgen
level Plasaminogen activiator inhibitor – 1
(PAI-1) level also falls (a prothrombotic factor).
Advantages of Troglitazone :
1. Once a day dosage
2. No dosage titration
3. No hypoglycaemia when used alone
4. No weight gain
5. Can be used along with sulphonyulurea,
Metformin and Insulin.
Hidden Benefits of Troglitazone:
1. Decrease in systolic, diastolic and mean blood
pressure.
2. Decrease in triglyceride level. This means (1+2)
indirectly a reduction in anti-hypertensive and
triglyceride lowering drugs.
3. Decreases PAI-1 level, a prothrombotic factor.
4. May prevent or delay beta cell exhaustion.
Recommendations:
Whatever be the benefits, while on Troglitazone,
patients liver enzymes are to be checked
periodically once a month initially and once in three
months subsequently. If the enzymes values are
more than three times of the normal value, the drug
should be discontinued at once.
For Further Reading:
1. Steven V. Edelman. Troglitazone: A new and unique oral
antidiabetic agent for the treatment of Type 2 diabetes an
the insulin resistance syndrome. Clinical Diabetes. 1997;
60-4.
2. Traglitazone may cause irreversible liver damage. News –
The Lancet 1997; 350: 1451.
3. Bailey CJ, Williams G, Pickup J. New Drugs in the
management of diabetes and its complications. In the Text
Book of Diabetes. Ed. Pickup J and Williams G.
Blackwell, London 1997; 84.5-6.
INSULIN SECRETAGOGUES
Beta Cell Secretory defect, namely the insulin
deficiency is an important factor in the pathogenesis
of Type 2 diabetes, particularly during later stages
of the disease. As the disease progresses, there is:
1. Loss of sensitivity of insulin secretion to a rise
in blood glucose concentration and
2. Impaired processing of pro-insulin.
Insulin secretagogues provide useful therapeutic
approaches if used early in the natural history of the
disease. An ideal insulin secretagogue would restore
beta cell sensitivity to glucose and at the same time
ensure adequate biosynthesis, processing and
secertion of insulin to other nutrients, hormones and
neural factors. Insulin secretagogues can be divided
into (i) Initiators of Insulin secretion eg. Glimepiride
and Repaglinide; (ii) Potentiator of insulin secretion
eg. GIP and GLP –1 (Gastric Inhibitory polypeptide,
Glucagon Like Peptide).
GLIMEPIRIDE
Glimepiride is a newer, novel second generation
sulphonylurea. It increases insulin secretion by
stimulating beta cells and also has significant
extrapancreatic activity.
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 28
1. Beta Cell Action:
Glimepiride binds to a specific receptor site 65 KDs
region in the beta cell while glibenclamide binds to
140 KDs region. Glimepiride binds to its receptor
2.5 to 3 times faster and dissociates from it binding
site 8 to 9 times greater than glibenclamide.
The mechanism of insulin secretion and release is
similar to gibenclamide ie. via the closure of ATP
dependent potassium channel and opening up of
voltage dependent calcium channel and increase of
intracellular calcuim concentration leading to
exocytosis of insulin.
Sulphonylureas act at the level of potassium – ATP
channel. However current sulphonylureas may not
stimulate beta cells in a controlled fashion or in
propotion to the blood glucose level, because of
their fixed blocking of potassuim-ATP channel.
Agents that accomplish this in a more flexible
fashion may lead to less secondary failure.
Glimepiride which binds to a differenct portion of
sulphonylurea receptor, leading to less fixed
blockage of potassium-ATP channel may have less
secondary failure.
The amount of insulin secretion is more or
equivalent to that of glibenclamide but the secretion
with glimepiride is very quick and lasts for a short
time than glibenclamide and hence there will be no
hyperinsulinism and reduced likelihood of inbetween
meal hypoglycaemia.
2. Insulin-independent blood glucose decreasing
activity of Glimepiride: (Extra-pancreatication):
Glimepiride exhibits a more pronounced insulin
independent blood glucose decreasing activity
compared to glibenclamide. This can be explained
by stimulation of glucose transport and nonoxidative
glucose metabolism and adipose tissue
and muscle cells. The increased glucose transporter
activity is brought out by increased translocation of
GLUT-4 isoform from inside the cell to surface of
adipocytes and muscle. It increases insulin
sensitivity and decreases insulin resistance. If
hyperinsulinemia is a concern in therapy of Type 2
diabetes, the higher insulin-independent blood blood
glucose decreasing activity of glimepiride might be
of therapeutic relevance.
Thus the more pronounced blood glucose decreasing
activity of glimepiride is brought out by its quick
insulin release in conjunction with an insulinindependent
glucose decreasing activity at the
periphery.
The extra pancreatic effects of glimepiride may
explain the lesser degree of insulin stimulation for a
given fall in blood glucose, in both short term and
longer clinical studies compared with other
sulphonylureas. In vitro, glimepiride stimulates
glycogen formation, glucose transport and other
insulin like effect. It decreases hepatic
gluconeogenesis.
There is not much difference in absorption whether
glimepiride is given just before or along with food.
The peak concentration of the drug is attained in one
hour. The half life of the drug is 9 hours. The drug is
100% bioavailable. It has dual mode of excretion
40% through liver and 60% through kidney. The
metabolites are not much active.
The quick insulin release, increased peripheral
tissue glucose disposal and the peak action at one
hour are responsible for smooth control of postprandial
hyperglycaemia. The prolonged half life
suggests that once daily dosing of glimepiride is
enough to maintain blood glucose control for 24
hours.
Efficacy wise glimepiride is equivalent to that of
glibenclamide. It decreases both fasting and post
prandial hyperglycaemia. The HbA1c decreases 1 to
2% within three months with 1 to 2 mg dose. The
fall in HbA1c is upto 3.5% when the drug is initiated
in diabetics with HbA1c more than 10.5%. There is
no increase in fasting C – peptide and insulin levels
even upto one year of treatment.
The hypoglycaemic episodes are very few in
number, lesser in intensity and are of shorter
duration. The hypoglycaemic episodes vary from
0.9 to 1.7% when compared to glipizide and
glibenclamide, both of which cause more severe
hypoglycaemic episodes.
Glimepiride safeguards the physiological
suppression of endogenous insulin release during
active physical exercise, implying that post exercise
induced hypoglycaemia may not occur with the
drug.
It has been observed in animal studies that platelet
inhibitory effect of glimepiride is much more
pronounced than gliclazide and hence it may have a
preventive effect in the development of
microvascular complications.
Dosage and Administration:
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 29
Glimepiride is indicated in Type 2 diabetics when
diet and exercise fails. Dosage is individualised for
each patient so as to achieve and maintain
satisfactory blood glucose level at a minimum
effective dose. The fasting blood glucose and
HbA1c measurements should be performed
periodically.
The usual starting dose of glimepiride is 1 mg.
Maximum initial dose 2 mg once daily taken just
before breakfast or with the first main meal of the
day. Further increments can be made at 1 or 2 week
intervals in increments of 2 mg. The patient’s blood
glucose response should guide dosage titration. The
usual maintenance dose is 1 to 4 mg once daily.
Maximum recommended dose is 8 mg once daily.
There is no need to split the dosage to twice daily.
Once daily dosage will improve patient’s
compliance.
Combination Therapy with Insulin :
For patients with secondary failure to other
sulphonylureas when glimepride and insulin therapy
is indicated, the recommended dosage of
glimepiride is 8mg once daily, Insulin is then
titrated from a low dosage upward with
approximately once-weekly dose increase guided by
fasting blood sugar measurements. Glimepiride
lowers daily insulin dosage requirements.
In Special Populations :
In American clinical trials, tight control ie. HBA1c
levels of 7.2% or lower was achieved in 68% of
obese diabetics and in 78% of diabetics with
hypertension.
No marked difference in the safety profile and daily
dosage were observed between patients who were
young and elderly, obese and non-obese, male and
female and among patients of various racial
phenotypes.
Glimepiride has less effect on cardiovascular system
than do glyburide and glipizide and has decreased
binding to cardiovascular ATP dependent potassium
channel causing one-third the degree of inhibition
seen with glyburide. There is also less alteration of
coronary blood flow. Thus interestingly, glimepiride
appears to be "Pancreas Specific" in its effect on the
potassium-ATP channel and hence it could be used
in cardiac patients with mild to moderate
hyperglycaemia.
Glimepiride should not be used in pregnancy and in
lactating mothers.
No clinically significant drug interactions were
observed with commonly used drugs such as
calcium channel blockers, ACE inhibitors, H2
receptors antagonists, fibrates, NSAID,
sympathomimetic agents, sulphonamides and
thyroid hormones.
Clinical studies indicate that glimepiride offers
significant benefits in the management of Type 2
diabetics.
1. It has the greatest (mgm. for mgm.) glucose
lowering effect when compared to other
sulphonylureas.
2. It achieves tight control in more than two thirds
of the patients.
3. It maintains effective control upto 2 1/2 years .
4. It reduces insulin resistance and has a unique
beta cell receptor binding capability.
5. Once daily dosage will improve patients
compliance.
6. It has insulin sparing activity. Glucose levels are
controlled without meaningful increase in
fasting insulin and in Type 2 diabetics requiring
exogenous insulin, glimepiride lowers daily
insulin dosage requirements.
For Further reading :
1. ZT Bloomgarden, New and Traditional
Treatment of Glycaemic in NIDDM. Diabetes
Care. 1996; 19:295 – 9.
2. Ronald B Goldberg, A dose response study of
Glimepiride in patients with NIDDM who have
previously received Sulphonylurea Agents.
Diabetes Care. 1996; 19 : 846-56.
3. Muller G. The Sulphonylurea --- Glimepiride ---
Diabetes 1993;42 : 1852-67.
4. Bailey CJ, Williams G, Pickup J. New drugs in
the management of diabetes and its
complications. In Text Book of Diabetes Eds.
Pickup J and Williams G., Blackwell, London,
1997; 84.8-11.
5. A Monograph on Glimepiride by Hoechst
Marion Roussel.
REPAGLINIDE---- PRANDIAL
GLUCOSE REGULATOR
INT. J. DIAB. DEV. COUNTRIES (1998), VOL. 18 30
Repaglinide is a non-sulphonylurea antidiabetic
agent and a short acting insulin secretagogue. It is a
benzoic acid derivative and is an analog of
meglitidine family.
The meglitidine shares the non-sulphonylurea
moiety of glibenclamide.
MODE OF ACTION:
Repaglinide has a unique binding site on beta cell,
different from that of glibenclamide. It acts via
closure of ATP dependent K channel in beta cell. It
to 3 to 5 times more potent insulin releaser than
glibenclamide but its action is short lived. The half
life of the drug is 2.5 hours and peak action is less
than one hour. It reduces post-prandial blood sugar
by 4 to 6 mmol and HbA1c by 2%. It is metabolised
in the liver and secreted in bile.
Repaglinide vs Glibenclamide:
When compared to glibenclamide, Repaglinide has
the following characteristic feature:
1. Fast Absorption
2. Short biological half life
3. Short duration of insulinotrophic activity
4. Lowest post-prandial Blood glucose
5. No in-between meal hypoglycaemia or
hyperinsulinemia.
Uses :
a) Primary Therapy in Type 2 Diabetes
Repaglinide is a prandial glucose regulator. It has a
fast onset and short duration of action. The initial
dose is 0.5 to 1 mg and gradually increased upto 2 to
4 mg. It should be administered three times a day
just, before along with or immediately after a meal
and offers greater flexibility in meal times and drug
dosing.
b) Useful in patients who eat at irregular times
or miss a meal:
Repaglinide increases insulin secretion sufficient to
control the post meal surge and not for so long as to
produce hypoglycaemia in-between meals and
especially when a meal is missed or delayed as is
the case with long acting insulinotrophic agents. So,
there is no in-between meal hypoglycaemia and
there is no in-between mean hyperinsulinemia.
The Other Notable Features of Repaglinide
Actions and Uses are:
1. The intermittent stimulation of K channel that
prevents down-regulation of receptors and
consequent refractoriness and secondary failure
of therapy.
2. It has no effect on ATP-regulated K channel of
cardiocytes or vascular smooth muscle cells
(Landry D. L. Oliver, Jan. 1992) and therefore
may be preferable to compounds that produce
this effect.
3. Rapid non-renal inactivation and elimination
results in a shortswift, "Antihyperglycaemia"
action. So, it can be administered safely in
patients with compromised early renal or
hepatic function.
Combination Therapy : Regaplinide and
Metformin:
Repaglinide acts only at beta cells leading to insulin
release, whereas metformin bypasses beta cell and
acts at periphery, liver, muscle and adipose tissue.
The actions are complementary to one another,
when both the drugs are combined. The fall in
HbA1c is significant within three months in most
Type 2 diabetics.
For Further Reading:
1. A D AAnnual Meeting 1997, Type 2 Diabetes, Diabetes
Care 1997 : 30(11): 1791-5.
2. A. Gradul et al Repaglinide, Drugs of the Future 1996 :
21(7): 694-9.
3. Malaise W. J. Stimulation of Insulin release by Non-
Sulphonylurea Hyperglycaemic agents – Hormone and
Metabolism Research 1995 : 27 :263-6.
4. Novo Nordisk Diabetes Update – 1997 & 1998.
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Some known and unknown facts about blood sugar and diabetes.
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