ORAL HYPOGLYCEMIC

DRUGS AND INSULIN

THERAPY FOR TYPE 2
DIABETES

DR FAIZA SHABBIR
PG (MU-I)
A.S.H
OVERVIEW
The goals of therapy for type 2 DM are similar
to type 1 diabetes.

However, type 2 is a progressive disorder and

ultimately requires multiple therapeutic agents
along with insulin because its specific
complications already present in up to 20-50%
of individuals when newly diagnosed.
MANAGEMENT OF DM 2
GLYCEMIC CONTROL

Diet/lifestyle
modifications
Exercise
Medications
SCREEN AND TREAT

Dyslipidemia Retinopathy
Hypertension Nephropathy
Obesity Neuropathy
Coronary heart Cerebrovascular events
disease
ORAL HYPOGLYCEMIC AGENTS
Biguanides

Insulin Secretagogues (sulphonyl urea/

nonsulphonylurea GLP1 agonist,DPP4
inhibitor)

Alpha glucosidase inhibitors

Thiazolidinediones
BIGUANIDES (METFORMIN)
decrease hepatic glucose production,improve
peripheral glucose utilization,lipid profile and
promote weight loss

 DOSE 500mg OD/BD upto 1000mg OD

 Side effects diarrhea, nausea, anorexia,

metallic taste, lactic acidosis

 C.I renal insufficiency, CHF, liver disease,

radiographic contrast material, severe illness
INSULIN SECRETAGOGUES
 Sulphonylurea

1st generation (chlorpropamide,

tolbutamide)
2nd generation (glimepride, glipizide,
glyburide)

 Non-sulphonylurea (repaglinide)

GLP1 agonist (exenatide, liraglutide)

INSULIN SECRETAGOGUES
Sulphonylurea
affect ATP sensitive K channels
Effective in recent onset T2DM <5year
1st generation (chlorpropamide, tolazamide
tolbutamide) have longer half life so rarely used
2nd generation (glimipride, glipizide, glyburide)
short half life.
DOSE 2mg to 4mg OD

Side effectshypoglycemia,weight gain

CI renal insufficiency
Non-Sulphonylurea DPP4 inhibitors (sitagliptin)
inhibits incretins(GLP) breakdown in intestinal
cells, hence stimulate insuin secretion.
DOSE 50 to 100mg OD

GLP agonist (leraglutide) improve satiety and

assist with weight loss.
DOSE inj 0.6 or 1.2 or 1.8mg S/C OD

Side effects nausea, vomiting, dizziness,

headache
ALPHA GLUCOSIDASE INHIBITOR
Acarbose Miglitol-decrease glucose
absorption from GIT,reduce
postprandial hyperglycemia

DOSE 25mg to 50mg with each

meal

Side effects diarrhea abdominal

distension LFTS derrange
THIAZOLIDINEDIONES
Roziglitazones 2-8mg OD
Pioglitazones 15-45mg OD
decrease insulin resistance,increase
glucose utilization,fat redistribution
from central to peripheral.

Side effect Fracture edema weight

gain
CI CHF, liver disease, pregnancy
Check LFTs every 2 months so use only
if DM not controlled by other drugs
Diet+Exercise + weight loss + Metformin

Reassess HbA1c (3 months) if abnormal

Metformin + one other agent

Reassess HbA1c (3 months) if still abnormal

Metformin + 2 other agents / insulin

INSULIN THERAPY
Use if
severe weight loss
acutely I'll or hospitalized
Renal disease/Liver disease
Failure of all agents

DOSE 0.5 to 1.0 Units/kg/day

Side effect hypoglycemia, weight gain,

injection site problems
>FBS (126mg/dl)
use NPH / Long acting (at bed time
only)

>RBS (180mg/dl)
Pre Lunch use Regular / Premixed
70/30
Pre Dinner use NPH / Long acting in
morning or premixed 70/30 pre
lunch.

Global hyperglycemia use basal

bolus regimen
EXAMPLE
In hospital, if patient is on (BASAL-BOLUS
REGIMEN) according to 0.5Units/kg/day
Regular insulin 6Units S/C TDS
NPH 12Units at 12:00AM
then 6*3=18Units so 12+18 = 30Units/day

After discharge on 70/30insulin make 2/3

morning dose 20 and 1/3 evening dose 10
(SPLIT-MIXED REGIMEN)
EMERGING THERAPY
Whole pancreas
transplantation
Pancreatic islet
cell
transplantation
Bariatric surgery
for obese
BMI>35kg/m°
COMPLICATIONS
Microvascular
Retinopathy/macular edema
Neuropathy (sensory/motor/autonomic)
Macro vascular
Coronary heart disease
Peripheral arterial disease
Cerebrovascular disease
Others
Uropathy gastroparesis dermatologic infections
cataract glaucoma
TREATMENT GOALS
HbA1c <7% (4-6% normal range)
Preprandial capillary plasma glucose
70-130mg/dl
Postprandial (2hours after meal) <180mg/dl
Blood pressure <130/80mg/dl
LDL 100mg/dL
HDL 40mg/dL
Triglycerides 150mg/dl

*American Diabetes Association

guidelines
Self monitoring of FBS/RBS daily
HbA1c 2-4 times/year
BP monitoring on routine visits
Foot inspection daily by patient

Annually
Eye examination
lipid profile
Serum creatinine
Urine microalbuminuria
AMERICAN DIABETES
ASSOCIATION (ADA)
GUIDELINES FOR T2DM 2016
Glycemic control is assessed by patient self-
monitoring of blood glucose (SMBG) and HbA1c
levels. Continuous monitoring of interstitial
glucose may be a useful adjunct in selected
patients on intensive insulin regimens.
Most patients receiving intensive insulin
regimens should consider SMBG before meals
and postprandially (occasionally), at bedtime,
before exercise, when they suspect low blood
glucose levels and before critical tasks, such as
driving.
HbA1c
The HbA1c test should be performed at least
twice a year in patients who meet treatment
goals and who have stable glycemic control,
quarterly in patients whose therapy has
changed or who are not meeting glycemic
goals.

Optimal diabetes care addresses behavioral,

dietary, lifestyle, and pharmaceutical
interventions.
A physical activity plan
should include at least
150 minutes of
moderate-intensity
aerobic activity per
week, reduce
sedentary time and
resistance training at
least twice per week
for most adults with
diabetes.
Newly diagnosed patients who are overweight
or obese should begin lifestyle modifications,
including physical activity, and be counseled to
lose at least 5% of their body weight.

If lifestyle efforts are not sufficient to maintain

or achieve glycemic goals, metformin therapy (if
tolerated or not contraindicated) should be
added at or soon after diagnosis.
Metformin is the preferred initial
pharmacologic agent. It is inexpensive, has a
long-established evidence base for efficacy and
safety, and may reduce risk for cardiovascular
events and death.

 Accumulating data suggest that metformin

therapy can be continued in patients with
declining renal function down to a glomerular
filtration rate GFR of 30 to 45 mL/min, although
the dose should be reduced.
Combination therapy when
monotherapy with a noninsulin agent
at the maximum tolerated dose not
achieve or maintain the HbA1c target over 3
months, a second agent should be added.

 Providers should consider a

combination of metformin and 1 of
these 6 treatment options:
sulfonylureas, thiazolidinediones,
dipeptidyl peptidase-4 inhibitors,
sodium–glucose cotransporter 2
(SGLT2) inhibitors, glucagon-like
peptide-1 (GLP-1) agonists or basal
Initial dual-regimen combination therapy
should be used when the HbA1c level is
9% or greater to more quickly achieve
glycemic control.

Insulin should be used with any

combination regimen in newly diagnosed
patients, timely dose titration is
important. Adjustment of both basal
and postprandial insulin should based
on SMBG levels montoring.
Basal insulin may be initiated at 10
units Hs or 0.5 to 1 units/kg/day with
metformin and perhaps with additional
noninsulin agent

Twice-daily premixed insulin analogues

(70/30 aspart mix or 75/25 or 50/50 lispro mix)
may also be considered

Inhaled insulin is
available for prandial
use but has a limited dose range. It is
contraindicated in patients with
chronic lung disease.
Atherosclerotic cardiovascular disease (ASCVD)
—defined as an acute coronary syndrome, a
history of myocardial infarction, stable or
unstable angina, coronary or other arterial
revascularization, stroke, transient ischemic
attack or peripheral arterial disease (PAD)—is
the leading cause of morbidity and mortality
for persons with diabetes.
Risk factors include dyslipidemia, hypertension,
smoking, a family history of premature coronary
disease and the presence of albuminuria.

Controlling individual cardiovascular risk factors

can prevent or slow ASCVD in persons with
diabetes. Large benefits are seen when multiple
risk factors are addressed simultaneously.
Blood pressure should be measured on routine
visits.

Persons with diabetes and hypertension should

have a blood pressure treatment goal of less
than 140/90 mmhg every routine visit.

In older, goal of less than 130/70 mmhg.

Patients with diabetes and hypertension
should consist of weight loss, reduced-sodium
diet, moderate alcohol intake and increased
physical activity. Pharmacologic therapy should
comprise a regimen that includes either an
angiotensin-converting enzyme inhibitor (ACEi)
or angiotensin receptor blocker (ARB) but not
both.

If ACE inhibitors, ARBs or diuretics are used,

serum creatinine levels, GFR and serum
potassium levels should be monitored.
In adults not receiving statins, it is reasonable
to obtain a lipid profile at the time of diabetes
diagnosis, at an initial medical evaluation, and
every 5 years thereafter.

Lifestyle modification should be recommended

to improve the lipid profile. This includes
focusing on weight loss, reducing intake of
saturated fat, trans fat, and cholesterol,
increasing intake of ω-3 fatty acids, fiber, plant
sterols and increase physical activity.
Lifestyle therapy should be intensified and
glycemic control optimized for patients with
elevated triglyceride level ≥150 mg/dL or low
HDL <40 mg/dL for men and <50 mg/dL for
women.

For patients with fasting triglyceride levels of

500 mg/dL or greater, evaluation for secondary
causes of hypertriglyceridemia should be done
and medical therapy should be considered to
reduce the risk for pancreatitis.
In addition to intensive lifestyle therapy, statin
use is recommended for most persons with
diabetes aged 40 years or older

Statin and fenofibrate considered if Triglyceride

204 mg/dL or greater
HDL 34 mg/dL or lower

Combination therapy with a statin and niacin

has not been shown to increase cardiovascular
benefit more than statin therapy alone. This
therapy may increase the risk for stroke and is
generally not recommended.
Aspirin therapy 75 to 150 mg/day
primary prevention strategy in patients with
T1DM and T2DM who are at increased
cardiovascular risk.

secondary prevention strategy in patients with

diabetes and a history of ASCVD.

If aspirin allergy, clopidogrel 75 mg/day should

be used.

Dual-antiplatelet therapy is reasonable for up to

a year after an acute coronary syndrome.
Annual diabetic kidney disease screening

urine albumin–creatinine ratio on a spot urine

sample

 GFR in all patients with T2DM+comorbid

hypertension.
Two of three urine albumin–creatinine ratio
specimens collected over 3 to 6 months should
be abnormal >30 mg/dl before a patient can be
considered to have albuminuria.

Patients with persistent and severely increased

levels of albuminuria ≥300 mg/dl are more
likely to develop end-stage renal disease.

Referral to a nephrologist should be considered

Optimizing glycemic control, blood pressure,
and serum lipid control is key to reduce the risk
and slowing the progression of diabetic
retinopathy.

Annual comprehensive eye examination by an

ophthalmologist should be done.
Achieving glycemic control can effectively
prevent or delay diabetic peripheral
neuropathy and may slow their progression but
it does not reverse neuronal loss.

Manifestations of diabetic autonomic

neuropathy include hypoglycemia unawareness,
gastroparesis, constipation, diarrhea, fecal
incontinence, erectile dysfunction, neurogenic
bladder, and sudomotor dysfunction.
The FDA has approved pregabalin, duloxetine,
and tapentadol for treatment of diabetic
peripheral neuropathy.

Tricyclic antidepressants, gabapentin,

venlafaxine, carbamazepine, topical capsaicin,
and tramadol may be considered as additional
treatment options.
All patients with T2DM should have a foot
examination annually using 10-g monofilament
testing plus pinprick sensation, vibration
perception or ankle reflexes, inspection of skin
integrity, identification of bony deformities, and
assessment of pedal pulses.

Patients with a history of foot ulceration or

amputation, foot deformities, peripheral
neuropathy, poor glycemic control, visual
impairment, and cigarette smoking are
considered to be at high risk should be
educated on proper foot care and the
importance of daily foot monitoring.
REFERENCE

American Diabetes Association 2016

(ADA) Guidelines Standards of Medical
Care in Diabetes Mellitus Type 2
[2016;39:S13-22]

http://care.diabetesjournals.org/content/3
9/Supplement_1/S13.pdf
55years old male came in opd for followup of
type2 DM. He feels well, exercising regularly,
good control of blood glucose on oral
metformin with HbA1c 6.2%. Regarding routine
screening tests which statement is correct?

a. dilated eye examination twice yearly

b. 24 hour urinary protien annually
c. home FBS measurement once per week
d. urine for microalbuminuria annually
50 years old woman came in opd with FBS
160mg/dl and 155mg/dl on two occasions.
HbA1c 7.8%. She has followed dietary
restrictions and exercise but her FBS remains
between 150-160mg/dl. She is asymptomatic,
physical examination and labs shows no
abnormality. First line treatment of choice in
this patient is?

a. Pioglitazones
b. Insulin glargine at bed time
c. Metformin
d. Encourage compliance with nutrition therapy