General Objectives of Diabetes Management:

To relieve symptoms
To correct associated health problems and to reduce morbidity, mortality and economic
costs of diabetes
To prevent as much as possible acute and long-term complications and to provide timely
intervention
To improve the quality of life and productivity of the individual ith diabetes
A. Diet
Diet is a basic part of management in every case! Treatment cannot be effective unless
adequate attention is given to ensuring appropriate nutrition
Dietary treatment should aim at:
a! ensuring eight control
b! providing nutritional requirements
c! alloing good glycaemic control ith blood glucose levels as close to normal as
possible
d! correcting any associated blood lipid abnormalities
The following principles are recommended as dietary guidelines for people with
diabetes:
Dietary fat should provide 25-35% of total intake of calories but saturated fat intake
should not e"ceed 10% of total energy! #holesterol consumption should be restricted
and limited to $%% mg or less daily!
&rotein inta'e can range beteen 10-15% total energy (%!)-* g+'g of desirable body
eight,! -equirements increase for children and during pregnancy! &rotein should be
derived from both animal and vegetable sources!
#arbohydrates provide 50-60% of total caloric content of the diet. #arbohydrates should
be comple" and high in fibre!
."cessive salt inta'e is to be avoided! /t should be particularly restricted in people ith
hypertension and those ith nephropathy!
!ercise
&hysical activity promotes eight reduction and improves insulin sensitivity, thus
loering blood glucose levels!
Together ith dietary treatment, a programme of regular physical activity and e"ercise
should be considered for each person! 0uch a programme must be tailored to the
individual1s health status and fitness!
&eople should, hoever, be educated about the potential ris' of hypoglycaemia and ho
to avoid it!
Mechanism of 2ction
0ulfonylureas interact ith receptors on pancreatic b-cells to bloc' 2T&-sensitive
potassium channels
This, in turn, leads to opening of calcium channels
3hich leads to the production of insulin
0econd Generation 0ulfonylureas
"lipi#ide
$!idi#ed to inacti%e metabolites
&alf-life - ' to ( hours
)otency - &igh
*'.5 to (0 mg+d,
."tended-release preparation- glipi4ide G/T0
Glipi4ide gastrointestinal therapeutic system
Does not induce eight gain
#linical 5ses of 0ulfonylureas
6ypoglycemic agents for treatment of Type 7 diabetes mellitus
2ct by increasing endogenous insulin secretion 8 not indicated for Type *
Most effective hen 9 cell function has not been severely compromised
/ncreased insulin secretion favors lipogenesis
Most appropriate in non- or mildly obese
5p to *:% ; of ideal body eight
#hoice of 0ulfonylurea
-onsider:
Duration of action, potency, metabolism, side effects
/n presence of renal dysfunction:
- Dual routes of elimination
Glyburide or glimepiride
- Metaboli4ed to inactive metabolites
Glipi4ide
0econd generation 05s bind nonionically to plasma albumin and have feer drug interactions
than earlier 05s, hich bind albumin ionically and compete ith other drugs for binding sites
<iguanides : improves insulin1s ability to move glucose into cells (esp! muscle,
- mechanism improves insulin sensitivity by increasing peripheral glucose upta'e
and utili4ation!
- =hou et al (7%%*, shoed that metformin stimulates the hepatic en4yme 2M&-
activated protein 'inase
- Metformin as first described in the scientific literature in *>?@ (5nger et al,!
- /t as first mar'eted in Arance in *>@> but did not receive AD2 approval for Type
7 diabetes until *>>B!
.etformin is a widely used monotherapy/ and also used in combination with the
sulfonylureas in treatment of type ' diabetes
<iguanides
Airst Generation- &henformin
&henethylbiguanide
2dverse .ffects
Cactic acidosis
-is' of cardio-
vascular disorder
#urrently in use in the 5!0!
-arely produces lactic acidosis e"cept under predisposing conditions
.echanism of action: antihyperglycemic
-orrect ele%ated hepatic glucose output
0nhibit gluconeogenesis
0nhibit glucose-1-phosphatase acti%ity glycogen sparing
insulin resistance
.ediated by acti%ation of 52A.)-acti%ated protein 3inase *A.)4, in
hepatocytes and muscle
Do not increase insulin secretion
5ot hypoglycemic/ e%en at high doses
Do not produce hypoglycemia
6econdary beneficial effects on lipids
7educed triglycerides
7educed total cholesterol
7educed 8D8
0ncreased &D8
0nsulin le%els unchanged or reduced
9eight loss/ some reduction of blood pressure
Appropriate for obese Type ' diabetics
!creted unchanged in the urine
&alf-life - appro!imately ' hours
Does not bind to plasma proteins
6hould not be used with renal or hepatic dysfunction
Also appro%ed for pre%ention of Type ' diabetes in high ris3 indi%iduals
:se also for polycystic o%ary syndrome: insulin resistance with o%arian
hyperandrogenism
Thia4olidinediones (T=D1s, : ma'e cells more sensitive to insulin (esp! fatty cells,
binds to and activates the gamma isoform of the pero"isome proliferator-activated
receptor (&&2-D,!
&&2-D is a member of the steroid hormone nuclear receptor superfamily, and is found in
adipose tissue, cardiac and s'eletal muscle, liver and placenta
upon activation of this nuclear receptor by a ligand such as a T=D, &&2-DEligand comple"
binds to a specific region of DF2 and thereby regulates the transcription of many genes
involved in glucose and fatty acid metabolism!
Thia4olidinediones: -osiglita4one
;ioa%ailability of oral dose is <<%
.etabolites ha%e no significant acti%ity
!creted in urine and feces
&alf-life: plasma half-life is = to ( hours !tensi%ely *<<.>%, bound to albumin
)otency: ( to > mg+day
As single dose or di%ided into ' doses
Troglita#one: '00 to 100 mg+day
5o e%idence of drug-induced hepatoto!icity
6hould not be used in patients who e!perienced ?aundice while ta3ing
troglita#one
Thia4olidinediones: &ioglita4one
6ome metabolites pharmacologically acti%e
!creted primarily in the feces
&alf-life: plasma half-life is = to @ hours
11 to '( hours for metabolites
!tensi%ely *A<<%, bound to albumin
)otency: 15 to (5 mg+day
"i%en as a single dose
5o e%idence of drug-induced hepatoto!icity
6hould not be used in patients who e!perienced ?aundice while ta3ing
troglita#one
Glpha E glucosidase inhibitors :
<loc' en4ymes that help digest starches sloing the rise in <!G!C!
a glucosidase inhibitors
.echanism of action:
competitive and reversible inhibitors of a glucosidase in the small intestine
Delay carbohydrate digestion and absorption
0maller rise in postprandial glucose
-linical use:
Aor mild to moderate fasting hyperglycemia ith significant postprandial hyperglycemia
Ta'en ith the first bite of a meal
Do not produce hypoglycemia or significant eight gain
.ffective regardless of age, genetic factors, body eight, duration or severity of disease
2carbose
Metaboli4ed ithin the digestive tract by en4ymes and intestinal bacteria
Co systemic bioavailability
H 7 ; is absorbed as intact molecule
2dverse effects: Gastrointestinal disturbances
Alatulence
Fausea
Diarrhea
5se gradual dose titration
#ontraindicated for inflammatory and obstructive boel disease, colonic ulcers
Meglitinides : 0timulate more insulin production I dependant upon level of glucose present
-epaglinide and Fateglinide
Mechanism of action:
t decrease 2T&-sensitive J
K
conductance
t 2dditional high affinity binding site identified in mouse 9-cells for repaglinide
2ction is glucose dependent
6igh potency
.licited insulin release is rapid and brief
t Ta'en ith meals for postprandial hyperglycemia
t -educed ris' of long-lasting hypoglycaemia
Dipeptidyl-&eptidase B /nhibitors
2gent in #lass: 0itagliptin, 0a"agliptin
Mechanism of action:
slos the inactivation of incretin hormones (glucagon-li'e peptide * and glucose-
dependent insulinotropic polypeptide,
/ncreases glucose-stimulated insulin secretion
#auses glucose-stimulated glucagon suppression
primarily loers postprandial glucose levels but has also been shon to reduce
fasting plasma glucose
D&&-/L inhibitors e"hibit both short term and long term actions of GC&-*
2ugment glucose induced insulin secretion
/nhibit glucagon secretion
0lo gastric emptying
/ncrease insulin biosynthesis
&romote beta cell differentiation
Oral 2gent Monotherapy
/f glycaemic control is not achieved (6b2*c M :!?; and+orI A&G M @!% mmol+C orI -&G
M**!%mmol+C, ith lifestyle modification ithin * E$ months, O-2C 2FT/-D/2<.T/#
2G.FT should be initiated!
/n the presence of mar'ed hyperglycaemia in nely diagnosed symptomatic type 7
diabetes (6b2*c M );, A&G M **!* mmol+C, or -&G M *B mmol+C,, oral anti-diabetic
agents can be considered at the outset together ith lifestyle modification!
As first line therapy:
Obese type 7 patients, consider use of metformin, acarbose or T=D!
Fon-obese type 7 patients, consider the use of metformin or insulin secretagogues
Metformin is the drug of choice in overeight+obese patients! T=Ds and acarbose are
acceptable alternatives in those ho are intolerant to metformin!
/f monotherapy fails, a combination of T=Ds, acarbose and metformin is recommended!
/f targets are still not achieved, insulin secretagogues may be added
#ombination Oral 2gents
#ombination oral agents is indicated in:
Fely diagnosed symptomatic patients ith 6b2*c M*%
&atients ho are not reaching targets after $ months on monotherapy