A short lecture highlighting the most important aspects of pharmacological management of DM in general. It discusses the use of insulin in type I diabetes mellitus and the approach with hypoglycemic agents in type II.

1. Management of Diabetes
Mellitus
Hasan Arafat
Medical House Officer
Cancer Care Center
Augusta Victoria Hospital

2. Introduction
• The primary focus in patients diagnosed with diabetes mellitus (DM)
is to prevent complications caused by hyperglycemia
• In the US, 57.9% of patients with DM have 1 ≥ diabetes-related
complications, 14.3% have ≥ 3
• Strict glycemic control is the primary method for reducing the
development and progression of the microvascular effects of DM
• Prevention of macrovascular complications requires aggressive
treatment of dyslipidemia and hypertension
• Self-monitoring of blood glucose (SMBG) and serum measurement of
HbA1c

3. Glycemic Control: SMBG
Recommendations for Target Glucose Levels in Nonpregnant Adults
Preprandial blood glucose levels 80-130 mg/dL
Peak postprandial levels <180 mg/dL
Hemoglobin A1c <7% (<6.5% in select patients if there is no significant
hypoglycemia
Pregnant patients require tighter control

4. Glycemic Control: HbA1c
• HbA1c measures nonreversible glycosylation of the hemoglobin
molecule
• It reflects mean blood glucose values during a 2-3 month period, can
be used as a predictor of a patient’s risk of microvascular
complications
• Limitations: hemoglobinopathies, anemia, sporadic episodes of
hypoglycemia and hyperglycemia

5. Glycemic Control: HbA1c
Correlation Between HbA1c and Mean Plasma Glucose Values
6 126
6.5 141
7 154
7.5 169
8 183
8.5 198
9 212
9.5 226
10 240
11 269
12 298

6. Pharmacologic Treatment: Noninsulin Therapies
• Is the patient insulin-deficient, resistant or both
• Noninsulin therapies:
• Insulin sensitizers
• Secretagogues
• Alpha-glucosidase inhibitors
• Incretins
• Pramlintide
• Bromocriptine
• Sodium-glucose cotransporter 2 (SGLT-2) inhibitors

7. Insulin Sensitizers
• Reduce glycemic load by improving insulin actions on peripheral
tissues
• Two classes are available:
• Biguanides
• Thiazolidinediones (TZD)
• Can by used as monotherapy or in combination with a sulfonylurea,
insulin, or each other

8. Insulin Sensitizers: Biguanides (Metformin)
• Main mechanism of action: suppression of hepatic glucose output
• Enhances insulin sensitivity of muscle and fat
• Mainly lowers fasting glycemia
• Some decreases in postprandial glucose are also observed
• Metformin does not cause hypoglycemia when used as monotherapy
• It causes weight loss
• Decreases plasma triglycerides concentration by 10% to 20%

9. Insulin Sensitizers: Biguanides (Metformin)
• Common side effect: GI distress
• Small increase in basal and postprandial lactate, rare but life-
threatening lactic acidosis (<1 in 100,000).
• Avoid in patients with creat >1.5 mg/dL in males, > 1.4 mg/dL or
higher

10. Insulin Sensitizers: Biguanides (Metformin)
• Metformin is usually dosed twice daily, can be dosed 3 times per day
• Typically started at 500 mg/day, max. dose: 2,550 mg/day
• Titer metformin, start with 500 mg at breakfast, increase by 500 mg in
weekly intervals until reaching a dose of 1,000 mg with breakfast and
dinner, helps GI side effects

11. Insulin Sensitizers: Thiazolidinediones
• Rosiglitazone and pioglitazone
• Mechanism of action: agonists of peroxisome proliferator-activated
receptor gamma (PPAR-γ)
• Enhance the sensitivity of muscle and fat, and mildly liver, to
exogenous and endogenous insulin, lowering fasting and postprandial
glucose
• Reduce triglycerides, increase HDL, increase LDL particle size

12. Insulin Sensitizers: Thiazolidinediones
• Cause weight gain, with an increase in SQ adiposity and fluid
retention
• Non-cardiogenic peripheral edema, occasionally cause heart failure
• Dose is effect dependent, avoid in class III or IV heart failure
• Increased bone fractures in women
• No hypoglycemia as monotherapy

13. Insulin Sensitizers: Thiazolidinediones
• Dosing is once daily
• Take 2-12 weeks to become fully effective
• Rosiglitazone: start at 4 mg/day, max. dose: 8 mg/day
• Pioglitazone: start at 15 mg/day, max.: 45 mg/day

14. Insulin Secretagogues
• Stimulate secretion of insulin from the pancreas
• Enhance glucose uptake by muscles and fat
• Decrease hepatic glucose production
• Two types:
• Sulfonylureas
• Glinides

15. Insulin Secretagogues: Sulfonylureas
• Lower fasting and postprandial glucose
• Divided into first and second generations
• 25% reduction in microvascular complications with or without insulin

16. Insulin Secretagogues: Sulfonylureas
• Cause weight gain (about 2 kg a few months after initiation)
• Hypoglycemia, can be significant necessitating medical care, can lead
to coma or seizure, usually in the elderly.

17. Insulin Secretagogues: Sulfonylureas
• Dosing is typically once or twice daily
• Caution should be used in patients with liver or kidney dysfunction or
in those who often skip meals

18. Insulin Secretagogues: Glinides
• Two drugs are available: nateglinide and repaglinide
• Their mechanism of action is similar to that of sulfonylureas, however,
their onset of action is more rapid and their duration is shorter
• A good option for patients with erratic timing of meals
• Lower risk for hypoglycemia

19. Insulin Secretagogues: Glinides
• Similar-to-lower risk of weight gain after therapy initiation
• Be cautious with patients with liver dysfunction
• Dosing is before meals

20. Alpha-Glucosidase Inhibitors
• Competitively blocks the enzyme alpha glucosidase at the brush
borders of the small intestine, delaying the absorption of
carbohydrates
• Primarily target postprandial hyperglycemia without causing
hypoglycemia
• Main side effects are GI
• Avoid in patients with hepatic or renal impairment
• Dosing is before carbohydrate-containing meals

21. Incretins
• Available as injections (glucagon-like peptide-1 [GLP-1} receptor
agonists) or oral formulations (dipeptidyl peptidase-4 [DPP-4]
inhibitors)
• All carry an increased risk of acute pancreatitis
• Patients should be educated regarding stopping the medication and
seeking medical advice if acute abdominal pain develops
• Increase the risk for thyroid C-cell tumors in patients with history of
medullary thyroid carcinomas or MEN-II

22. Incretins: GLP-1 Receptor Agonists
• Stimulate insulin secretion and suppress glucagon secretion after
meals in a glucose-dependent manner
• Short-Acting (4-6 hrs)
• Exenatide: a synthetic form of exendin 4, a hormone found in the saliva of the
Glia monster
• It delays gastric emptying and suppresses appetite through central pathway
• Decreases postprandial blood glucose levels, with moderate reduction in
fasting blood glucose levels also occur

23. Incretins: GLP-1 Receptor Agonists
• Short-Acting (4-6 hrs)
• Major side effects are GI
• Hypoglycemia does not occur when used as a monotherapy or with
metformin, but occurs in combination with sulfonylurea
• Causes weight loss up to 2-3 kg within the first 6 months, up to 5.5 kg in the
first 2 years
• No data regarding cardiovascular impact
• Dosing is twice daily 60 minutes before the 2 main meals, start with 5 mcg,
titrate to 10 mcg after 1 month

24. Incretins: GLP-1 Receptor Agonists
• Intermediate-Acting:
• Liraglutide, derived from human GLP-1
• Administer once daily SQ
• Timing is independent of meals
• Half-life is 13 hours
• Similar benefits and side effects of exenatide
• Initial dose: 0.6 mg/day for a week, increase to 1.2 mg/day
• Increase to 1.8 mg/day after another week
• Protective cardiovascular effect

25. Incretins: GLP-1 Receptor Agonists
• Long-Acting:
• Exenatide is available as a once per week SQ injection (extended-release
exenatide)
• If dose is missed, it should be administered as soon as possible
• Albiglutide is a new GLP-1 analog with a half-life of 4-7 days
• Dosing is 30-50 mg/week SQ
• Dulaglutide is another long-acting GLP-1 analog
• Dosing is 0.75 or 1.5 mg/ week SQ

26. Incretins: DPP-4 Inhibitors
• Dipeptidyl peptidase-4 (DDP-4) is a cell membrane protein that
rapidly degrades GLP-1 and glucose-dependent insulinotropic
polypeptide.
• Suppression leads to higher levels of insulin secretion and
suppression of glucagon secretion in a glucose-independent manner
• Their effect are primarily on postprandial blood glucose, with some
reduction in fasting glycemia

27. Incretins: DPP-4 Inhibitors
• Sitagliptin (Januvia)
• Dosing is 100 mg PO OD with/without meals
• Adjust in patients with renal impairment
• CrCl: 30-50 mL/min: dose: 50 mg PO OD
• CrCl: <30 mL/min, dose: 25 mg PO OD
• Saxagliptin:
• 2.5-5 mg PO OD with/without meals
• eGFR: <50 mg/mL, or those on strong P450 3A4/5 (ketoconazole, ritonavir)
• Linagliptin:
• 5 mg PO OD, dose adjustment not necessary with renal impairment
• Alogliptin
• 25 mg PO OD
• 12.5 mg PO OD if CrCl: 30-60 mL/min
• 6.25 mg PO OD if CrCl: <30 mL/min

28. Incretins: DPP-4 Inhibitors
• Generally well tolerated
• Most common side effect: headache
• Some report nasopharyngitis
• Weight-neutral
• Does not cause hypoglycemia as monotherapy or when combined
with metformin/thiazolidinediones
• At risk for hypoglycemia when combined with sulfonylurea or insulin

29. Pramlintide
• A synthetic form of amylin, a hormone secreted by beta cells that
suppresses glucagon secretion, slows gastric emptying, and
suppresses appetite through central pathways.
• Primarily affects postprandial blood glucose

30. Pramlintide
• Only approved as adjunctive therapy with insulin
• Reduces insulin requirement by up to 50%
• Starting dose is 50 ug SQ before meals in DM-II
• 15 ug before meals in DM-I
• Can by used with metformin or sulfonylureas

31. Pramlintide
• Major side effects are GI, especially nausea and hypoglycemia
• Causes weight loss of 1-1.5 kg over 6 months, up to 4.5 kg with
chronic therapy

32. Bromocriptine
• Fast-release bromocriptine improves glycemic control in DM-II when
taken within 2 hours of waking up
• Unknown mechanism of action
• Improves HbA1c by 0.6%-0.7%
• Available as 0.8 mg oral tablet, therapeutic dose varies from 1.6 to 4.8
mg
• Nausea is the main side effect

33. SGLT-2 Inhibitors
• A protein acting as sodium-glucose cotransporter in the kidney’s
proximal tubules
• Leads to excretion of glucose in the urine at much lower blood
glucose levels than normal (app. 120 mg/dL instead of 180 mg/dL)
• Indicated as an adjunct to diet and exercise to improve glycemic
control in patients with DM-II

34. SGLT-2 Inhibitors
• Canagliflozin
• 100 mg/day before the first meal, can be increased to 300.
• Max. dose is 100 mg in eGFR: 45-60 mL/min/1.73 m2
• C/I in eGFR < 45 mL/min/1.73 m2
• Dapagliflozin (forxiga)
• 5 mg/day, can be increase to 10 mg/day
• C/I in eGFR < 60 mL/min/1.73 m2
• Empagliflozin
• 10-25 mg PO OD, c/I in eGFR < 60 mL/min/1.73 m2
• Only antidiabetic to reduce CVS risk

35. Noninsulin Therapies
Subgroup Generic name Route Comments
Insulin sensitizers
Biguanides Metformin Oral Weight loss
No hypoglycemia
GI upset
Thiazolidinediones Rosiglitazone
Pioglitazone
Oral Weight gain
Peripheral edema
Insulin secretagogues
Sulfonylureas Chlorpropamide
Glimepiride
Glyburide
Tolazamide
Glyburide
Oral Hypoglycemia
Weight gain
Glinides Nateglinide
Repaglinide
Oral Weight gain

36. Noninsulin Therapies
Alpha-glucosidase inhibitors
Acarbose
Miglitol
Oral GI upset
No hypoglycemia
Incretins
GLP-1 receptor agonists
Short acting (4-6 hrs) Exenatide SQ Weight loss
GI upset
Intermediate-acting (24 hrs) Liraglutide SQ Weight loss
Nausea
Long-acting (7 days) Exenatide ER
Albiglutide
Dulaglutide
SQ Weight loss
Nausea
DPP-4 inhibitors Sitagliptin
Saxagliptin
Linagliptin
Alogliptin
Oral No hypoglycemia
Nasopharyngitis
Weight neutral

37. Noninsulin Therapies
Others
Pramlinitide Pramlinitide SQ Weight loss
GI upset
Adjunctive treatment
with insulin
Rapid-release
bromocriptin
Bromocriptin Oral Take within 2 hours of
awakening
Nausea, stuffy nose
SGLT-2 inhibitors Canagliflozin
Dapagliflozin
Empagliflozin
Oral Polyuria UTIs

38. Insulin
• The first treatment of diabetes
• Regulates glucose metabolism and is the most effective method of
reducing hyperglycemia
• No upper limit in dosing
• Reduces triglycerides and increases HDL
• Weight gain is a problem, typically increases weight by 2-4 kg
• Hypoglycemia is a concern

39. Insulin Onset Peak Effective Duration
Ultra-rapid analog (URAA) ~1 min 57 min 5 hr
Rapid-acting analog (RAA)
Aspart (novolog) 5-15 min 30-90 min <5 hr
Lispro (Humalog) 5-15 min 30-90 min <5 hr
Glulisine (apidra) 5-15 min 30-90 min < 5hr
Short-acting
Regular insulin (Humulin R, Novolin R) (R) 30-60 min 2-3 hr 5-8 hr
Intermediate-acting, basal
Insulin NPH (N) 2-4 hr 4-10 hr 10-16 hr
Long-acting analog (LAA), basal
Insulin glargine (lantus, toujeo, basaglar) 2-4 hr No peak 20-24 hr
Insulin detemir (Levemir) 3-8 hr No peak 6-23 hr
Insulin degludec (Tresiba) 1 hr >25 hr
Premixed
75% insulin lispro protamine/25% insulin lispro (Humalog mix 75/25) 5-15 min Dual 10-16 hr
50% insulin lispro protamine/50% insulin lispro (Humalog mix 50/50) 5-15 min Dual 10-16 hr
70% insulin lispro protaine/50% insulin lispro (Humalog mix 50/50) 5-15 min Dual 10-16 hr

40. Insulin: Basal-Bolus
• Combines a long-acting agent (administered once or twice daily) that
provides basal insulin needs and a rapid-acting agent for prandial
coverage
• Traditionally, 50% of daily total dose is given as glargine or detemir
• The rest is provided as prandial insulin before meals
• Prandial insulin can be fixed, but it’s better to determine the dose
based on CHO content of the meal
• Starting dose: 0.3 U/kg total daily
• Monitor via SMBG

41. Type I DM
Initial basal dose (detemir or glargine) 10 U or 0.15
U/kg (whichever is greater
Adjustments (desired range 90-140 mg/dL):
increase/decrease by 3 units every 3 days if out of
range
Initial basal coverage (NPH insulin): 10 U or 0.15 U/kg
divided into 2 doses; 1 at breakfast and 1 at dinner
Adjustments (desired range 90-140 mg/dL):
increase/decrease by 10% every 3 days, if out of range
Meal coverage (regular insulin, glulisine, aspart, lispro)
4 units per kg or 0.15 U/kg divided among 3 meals
Adjustments (postprandial <180 mg/dL);
Increase/decrease by 1 unit or 10% (whichever is
greater)
CHO counting (1 unit per 15 g of CHO) Increase to 1 unit per 10 g of CHO or decrease to 1
unit per 20 g of CHO

42. Insulin Pump Therapy
• Allows administration of different basal insulin rates during different
periods of the day
• Allows administration of the meal bolus as a single discrete bolus or
as an extended bolus (square bolus) over a specific time
• Provides a better match between insulin delivery and glucose
absorption from the meal in patients with gastric emptying
abnormalities

43. Insulin Pump Therapy: Indications
• Patients unable to achieve target goals with basal-bolus regimens
• Frequent hypoglycemia, dawn phenomenon, or brittle diabetes
• Pregnant patients
• Patients with insulin sensitivity or those requiring more intense
monitoring due to complications
• Patients able to monitor blood glucose several times during the day
and to make insulin dose adjustments

44. Examples of SQ Insulin Regimens
Regimen Timing and distribution Advantages Disadvantages Adjusting doses
Regimen that more closely mimic normal insulin secretion
Insulin pump
therapy
Basal delivery of URAA
or RAA, generally 40-
60% of TDD
Mealtime and
correction: URAA or
RAA by bolus-based on
ICR and/or ISF and
target glucose, with pre-
meal insulin ~ 15 min
before eating
Can adjust basal
rates for varying
insulin
sensitivity by
time of day, for
exercise and for
sick days
Flexibility in
meals timing
and content
Pump can
deliver insulin in
increments of
fractions of units
Most expensive
regimen
Must continuously
wear one or more
devices
Risk of rapid
development of
ketosis or DKA with
interruption of
insulin delivery
Potential reactions
to adhesives and
site infection
Technically complex
approach
Mealtime insulin: if
CHO counting is
accurate, change
ICR if glucose after
meal consistently
out of target
Correction insulin:
adjust ISF and/or
target glucose if
correction does not
consistently bring
glucose into range
Basal rate: adjust
based on overnight,
fasting or daytime
glucose outside of
activity of
URAA/RAA bollus

45. MDI: LAA + flexible
doses of URAA or
RAA at meals
LAA once daily
(insulin detemir or
insulin glargrin may
require twice-daily
dosing): generally
50$ of TDD
Mealtime and
correction: URAA or
RAA based on ICR
and/or ISF and
target glucose
Can use pens for all
components
Flexibility in meal
timing and content
Insulin analogs
cause less
hypoglycemia than
human insulins
At least four daily
injections
Most costly insulins
Smallest increment
of insulin is 1 U (0.5
U with some pens)
LAA may not cover
strong dawn
phenomenon (rise
in glucose in early
morning hours) as
well as pump
therapy
Mealtime insulin: if
CHO counting is
accurate, change
ICR if glucose after
meal consistently
out of target
Correction insulin:
adjust ISF and/or
target glucose if
correction does not
consistently bring
glucose into range
LAA: based on
overnight or fasting
glucose or daytime
glucose outside of
activity time course,
or URAA or RAA
injections

46. MDI regimens with less flexibility
Four injections
daily with fixed
doses of N and
RAA
Pre-breakfast: RAA
~20% of TDD
Pre-lunch: RAA ~
10% of TDD
Pre-dinner: RAA
~10% of TDD
Bedtime: N ~ 50% of
TDD
May be feasible if
unable to CHO count
All meals have RAA
coverage
N is less expensive
than LAAs
Shorter duration:
RAA may lead to
basal deficit during
day, may need
twice-daily N
Greater risk of
nocturnal
hypoglycemia with
N
Requires relatively
consistent meal
time and CHO intake
Pre-breakfast RAA:
based on BGM after
breakfast or before
lunch
Pre-lunch RAA:
based on BGM after
lunch or before
dinner
Pre-dinner RAA:
based on BGM after
dinner or at
bedtime
Evening N: based on
fasting or overnight
BGM

47. Four injections daily
with fixed doses of
N and R
Pre-breakfast:
~20% of TDD
Pre-lunch: R~10%
of TDD
Pre-dinner: R~10%
of TDD
Bedtime: N~50% of
TDD
May be feasible if
unable to CHO count
R can be dosed
based on ICR and
corrections
All meals have R
coverage
Least expensive
insulins
Greater risk of
nocturnal
hypoglycemia with
N
Greater risk of
delayed post-meal
hypoglycemia with R
Requires relatively
consistent
mealtimes and CHO
intake
R must be injected
at least 30 min
before meal for
better effect
Pre-breakfast R:
based on BGM after
breakfast or before
lunch
Pre-lunch R: based
on BGM after lunch
or before dinner
Pre-dinner R: based
on BGM after dinner
or at bedtime
Evening N: based on
fasting or overnight
BGM

48. Regimens with fewer daily injections
Three injections:
daily N+R or N+RAA
Pre-breakfast: ~40%
N + ~15% R or RAA
Pre-dinner: ~15% R
or RAA
Bedtime: 30% N
Morning insulins
can be mixed in one
syringe
May be appropriate
for those who
cannot take
injection in middle
of day
Morning N covers
lunch to some
extent
Same advantages of
RAAs over R
Least (N+R) or less
expensive insulins
than MDI with
analogs
Greater risk of
nocturnal
hypoglycemia with
N than LAAs
Greater risk of
delayed post-meal
hypoglycemia with R
than RAA
Requires relatively
consistent
mealtimes and CHO
intake
Coverage of post-
lunch glucose often
suboptimal
R must be injected
at least 30 min
before meal for
better effect
Morning N: based
on pre-dinner BGM
Morning R: based
on pre-lunch BGM
Morning RAA: based
on post-breakfast or
pre-lunch BGM
Pre-dinner R: based
on bedtime BGM
Pre-dinner RAA:
based on post-
dinner or bedtime
BGM
Evening N: based on
fasting BGM

49. Twice-daily “split-
mixed”: N+$ or
N+RAA
Pre-breakfast: ~40%
N + ~15% R or RAA
Pre-dinner: ~ 30% N
+ ~ 15% R or RAA
Least number of
injections for people
with strong
preference for this
Insulin can be mixed
in one syringe
Least (N+R) or less
(N+RAA) expensive
insulin vs analogs
Eliminates need for
doses during the
day
Risk of
hypoglycemia in
afternoon or middle
of night from N
Fixed mealtime and
meal content
Coverage of post-
lunch glucose often
suboptimal
Difficult to reach
targets for blood
glucose without
hypoglycemia
Morning N: based
on pre-dinner BGM
Morning R: based
on pre-lunch BGM
Morning RAA: based
on post-breakfast or
pre-lunch BGM
Evening R: based on
bedtime BGM
Evening RAA: based
on post-dinner or
bedtime BGM
Evening N: based on
fasting BGM

51. DM-II
• Starting daily dose is typically 0.5 U/kg total, divided between long-
acting and rapid-acting
• Can be combined with insulin sensitizers but not secretagogues

52. DM-II
Initial basal dose (detemir or glargine) 15 units or 0.25
U/kg (whichever is greater
Adjustments (desired range 90-140 mg/dL);
increase/decrease by 3 units or 10% (whichever is
greater) every 3 days, if out of range
Initial basal coverage (NPH insulin) 15 U or 0.25 U/kg
divided into 2 doses; 1 given at breakfast and 1 at
dinner
Adjustments (desired range 90-149 mg/dL);
increase/decrease by 10% every 3 days, if out of range
Meal coverage (regular insulin, glulisine, aspart, lispro)
6 units per meal or 0.25 U/kg divided between 3
meals
Adjustments (postprandial <180 mg/dL);
increase/decrease by 2 units or 10% (whichever is
greater)
CHO counting (1 unit per 10 g of CHO) Increase to 1 unit per 5 g of CHO or decrease to 1 unit
per 15 g of CHO

53. Initiation, Titration
Insulin
Regimen
HbA1c Medication Pattern Diet lifestyle Monitoring
Basal-only >7.5-10 Oral
medications
adequately
control
postprandial
glucose
excursions
High fasting
glucose with
minimal
glucose rise
during the
day
Small, regular
meals; large
meals will
result in
postprandial
hyperglycemi
a
Reluctance to
do MDI;
requires oral
agents
Fasting
Basal-bolus
(MDI)
>7.5 Regimen can
be matched
to any pattern
to achieve
glycemic
control
Regimen can
be matched
to any diet to
achieve
glycemic
control
Erratic
schedule,
motivated to
achieve tight
glycemic
control
Frequent
blood glucose
monitoring
(minimum
before meals
and bedtime)

54. Once- or Twice-Daily Premixed
Rapid-acting
analogue and
intermediate
acting
>7.5 Oral agent
failure (max.
tolerated
dosages,
contraindicati
ons, cost
issues)
Any fasting
glucose,
glucose rises
during the
day
Large
suppers,
small lunches
Consistent
daily routine,
reluctance to
do MDI
Fasting and
pre-supper (if
insulin is
administered
twice daily)
Regular and
NPH
>7.5 Oral agent
failure (max.
tolerated
dosages, c/I,
cost issues
Any fasting
glucose,
glucose rises
during the
day
Isocaloric
meals or
larger lunches
Consistent
daily routine,
reluctance to
do MDI
Fasting and
pre-supper (if
insulin is
administered
twice daily)

55. Summary
• Glycemic control is crucial for preventing microvascular and
macrovascular complications of DM
• DM-II is a progressive disease and requires therapy intensification
with time
• Insulin sensitizers and incretin-based therapy should be used early in
the course of DM-II
• Patients with DM-I require insulin therapy, some with advanced DM-II
require insulin
• Multiple daily doses of insulin providing basal, prandial and
supplemental insulin are the mainstay of insulin therapy