Diabetes Mellitus Type 2 Treatment
Table 1. Diagnosis criteria
Table 2. Treatment goals
Table 3. Oral diabetic medications
Clinical judgment may supersede the use of this treatment algorithm
Diagnosis of Type 2 DM
Provide Medical Nutrition Therapy (MNT) & Diabetes Self Management Training
(DSMT). Promote physical activity, SMBG and risk reduction education.
FPG  200 mg/dl with or without symptoms
FPG < 200 with symptoms
FPG < 200 mg/dl without
symptoms
Continue MNT and exercise without
medication for 4-8 weeks
HgbA1C
< 7.0 %
HgbA1C
 7.0 %
Reassess
in 3 months
HgbA1c  8.5%
HgbA1C 7.0 - 8.5%
*May consider initiation of monotherapy
when HgbA1C 6.6% - 7.0% if symptoms or
risk factors present for end organ damage
Monotherapy
Initiate Secretagogue OR Insulin Sensitizer
Dual Therapy
Initiate Secretagogue AND Insulin Sensitizer
 Consider a sulfonylurea if BMI < 25 kg/m2 OR
metformin* if BMI  25 kg/m2
 Consider a miglitnide if FPG at goal, but post-prandial
blood glucose elevated
 Consider initiation of oral agent plus bedtime basal
insulin if symptoms of polyuria, polydipsia, weight
loss or end organ damage present
 Reassess every 1-2 weeks; if fasting blood glucose
remains elevated see table 3 for dose titration
* Do not use metformin if SCr > 1.5 in males, SCr > 1.4 in females,
CHF or COPD, liver disease or current alcoholics
If contraindications; see additional therapy below
 Reassess every 1-2 weeks; if fasting blood glucose
remains elevated see table 3 for dose titration
 Initiation of insulin therapy also acceptable at this time
No
Yes;
Reassess
in 3 months
Glycemic goals met
within 4 - 12 weeks
Glycemic goals met
within 4 - 12 weeks
No
Additional Therapy
 Insulin Therapy (Appendix A) with bedtime NPH or Glargine Insulin
Yes;
Reassess
in 3 months
 Thiazolidinediones* (rosiglitazone or pioglitazone) - Do not use in liver disease or CHF
 Consider using if FPG at goal, but post-prandial blood glucose remains elevated
Meglitinide* (repaglinide or naglitanide) - Do not combine with sulfonylurea
OR
Alpha glucosidase inhibitors* (acarbose or miglitol)
*Reassess every 1-2 weeks; if fasting blood glucose remains elevated see table 3 for dose titration
Yes;
Reassess
in 3 months
Glycemic goals met
within 4 - 12 weeks
No
Insulin Therapy (Appendix A)
Table 1. Criteria for diagnosis of diabetes*
Fasting Plasma Glucose  126 mg/dl
Casual Plasma Glucose  200 mg/dl plus symptoms (polyuria, polydipsia, unexplained weight loss)
Oral Glucose Tolerance Test 2 hour PG  200 mg/dl (75 g anhydrous glucose)
Hyperglycemia not diagnostic for diabetes
Impaired fasting glucose (IFP) FPG  110 and < 126 mg/dl
Impaired glucose tolerance (IGT) 2 hour PG  140 and < 200 mg/dl
* Verify on subsequent day if no symptoms present
Table 2. Treatment recommendations and goals for diabetes
Clinical Practice Recommendations. Diabetes Care;26 suppl 1: January 2003.
Glycemic Control
HgbA1c
<7%
Monitor baseline, q 3 months until goal met then q 6 months
Plasma blood glucose
Whole blood glucose
Blood Pressure
Lipids
LDL
Triglycerides
HDL
Visual Foot Inspection
Monofilament Foot Exams
Dilated Eye Exams
Urine Protein Testing
Vaccinations
Fasting 90-130 mg/dl
Post-prandial < 180 mg/dl
Fasting 80-120 mg/dl
Post-prandial < 170 mg/dl
< 130/80 mmHg
< 125/75 mmHg for proteinuria (> 1gram/day)
Monitor at least yearly; Q 3-6 months if treatment needed
< 100mg/dl
< 150 mg/dl
> 40 mg/dl
Quarterly
Annually
Annually
Annually
Flu vaccine yearly
Pneumonia vaccine ONCE
(repeat once > 65 yo. if previous vaccine was > 5 years prior)
Table 3. Oral Diabetes Medications (Bolded are UPMC Health Plan preferred agents)
Agent & Strength
Initial dose
Dose titration
Maximum dose
Contraindications/
Special Considerations
40 mg/day: give in two
divided doses when
doses reaches
15 mg/day
20 mg: give in one or
two doses
 Renal dysfunction: do not use if
ClCr < 10 ml/min
 Hepatic dysfunction: use
conservative dosing
 Administer 30 minutes before meals
 Monitor for s/sx hypoglycemia
Secretagogues
Sulfonylureas (do not use if hypersensitivity to sulfonamides)
Glipizide - short-acting
(Glucotrol)
5 mg, 10 mg
2.5 mg/day
Increase by 2.5 - 5 mg/day every
1-2 weeks
Glipizide – ext. release
(Glucotrol XL)
2.5 mg, 5 mg, 10 mg
Glimepiride
(Amaryl)
1 mg, 2 mg, 4 mg
5 mg/day
(2.5 mg if elderly
or liver disease)
1-2 mg daily with
breakfast or first
main meal
Increase dose by 2.5 - 5 mg/day no
more often than every 1-2 weeks
Increase at 1-2 mg/day increments
every 1-2 weeks
8 mg daily
 Renal dysfunction: use with caution if
ClCr < 20ml/min
 Elderly: use conservative dosing
 Take with breakfast or first main meal
 Monitor for s/sx hypoglycemia
NOTE: Glyburide is not recommend as first line sulfonylurea. Glyburide offers no benefit over Glipizide or Glimepiride and may cause more hypoglycemia as well
as an increase in potential drug-drug interactions.
Glyburide
2.5 mg/day
Increase by 2.5 mg/day every
20 mg; give in one or
 Renal dysfunction: do not use if
(1.25 mg/day if
1-2 weeks
two divided doses
(Diabeta, Micronase)
ClCr < 50ml/min
elderly or liver
(elderly/liver disease increase by
1.25 mg, 2.5 mg, 5mg
 Hepatic dysfunction use
disease)
1.25-2.5 mg/day every 1- 3 weeks)
conservative dosing
Glyburide microcrystalline
1.5 mg/day
Increase by 1.5 mg/day every
12 mg; If taking more
 Administer with meals
(0.75-1.5 mg/day
1-2 weeks
than 6 mg daily give in
(Glynase Prestab)
 Monitor for s/sx hypoglycemia
if elderly or liver
two divided doses
1.5 mg, 3 mg, 4.5 mg, 6 mg
disease)
Agent & Strength
Initial dose
Dose titration
Maximum dose
Contraindications/
Special Considerations
Adjustment based on fasting blood
glucose response. Double
preprandial dose until 4 mg reached
for single dose. Allow at least one
week between dose adjustments.
16mg daily; no more
than 4 mg per dose
(4mg qid with meals)
60-120 mg tid 30
minutes before
meals
If started on 60 mg tid may increase
to 120 mg tid after 2-4 weeks of
therapy
120 mg tid
 Patient should skip dose if meal is
skipped to avoid hypoglycemia
 Take 15 minutes before meals,
(effectiveness  if taken > 30min prior)
 Renal dysfunction: CrCl < 40ml/min
begin with 0.5 mg and titrate cautiously
 Hepatic dysfunction: use with caution
 Monitor for s/sx hypoglycemia
 Patient should skip dose if meal is
skipped to avoid hypoglycemia
 Elderly: start at 60mg dose
 Monitor for s/sx hypoglycemia
500 mg with
breakfast
500 mg/day at weekly intervals,
adding a dose at dinner and then at
lunch as tolerated
2550 mg/day
(850 mg tid)
Meglitinides (no benefit in combination with sulfonylureas)
Repaglinide
(Prandin )
0.5 mg, 1 mg, 2 mg
HgA1c < 8%
0.5 mg bid or tid
with meals
HbA1c > 8 %
1 mg or 2 bid or
tid with meals
Nataglinide
(Starlix)
60 mg, 120 mg
Insulin Sensitizers
Biguanide
Metformin
(Glucophage)
500 mg, 850 mg, 1000 mg
Elderly will not likely
tolerate high doses
(Glucophage XR )
500 mg
Doses > 2000 mg may
increase side effects
with little benefit on
blood glucose
Contraindications:
 SCr > 1.5 mg/dl (males) OR
SCr > 1.4 mg/dl (females)
 Acute or chronic metabolic acidosis
 Hepatic dysfunction or known
current alcohol abuse
 COPD or CHF (moderate/severe)
Monitoring:
 GI intolerance
 Diffuse muscle weakness
Thiazolidinediones
Rosiglitazone
(Avandia)
2 mg, 4 mg, 8 mg
4 mg qd or
2 mg bid
May increase to 4 mg bid or 8 mg
qd after 12 weeks
8mg daily
Pioglitazone
(Actos)
15 mg,30 mg, 45 mg
15 mg qd
may increase by 15 mg qd every 3
months based on HgA1c response
45 mg daily
monotherapy
30 mg daily
combination therapy
Contraindications:
 Hepatic dysfunction: Do not use if
ALT > 2.5 the upper limits of normal.
 Type I diabetes
Cautions:
 NYHA class III/IV heart failure; may
cause fluid retention
 Anemia; may worsen blood counts
 May adversely effect lipids
 LDL cholesterol (rosiglitazone only)
 May cause resumption of
ovulation in premenopausal
anovulatory women
Monitoring:
 LFTs: baseline and then q 2 months
for 1 year then periodically.
 Fluid retention
 Menstrual irregularities
Other oral agents
Alpha-glucosidase Inhibitors
Acarbose
(Precose)
25 mg, 50 mg, 100 mg
Miglitol
(Glyset)
25 mg, 50 mg and 100 mg
25 mg tid with
first bite of meals
May start at
25 mg qd if GI
distress noted
Increase dose to 50 mg tid with
meals after 4-8 weeks if necessary.
Some may benefit from further
increasing the dosage to 100 mg tid
if tolerated.
100 mg tid with meals
for patient > 60 kg.
50 mg tid with meals for
pts  60 kg.
100 mg tid
Contraindications:
 Liver dysfunction: may  ALT/AST
(Acarbose only)
 Bowel disorders: inflammatory bowel
disease, colonic ulcer, partial
obstruction, chronic intestinal problems
 Renal dysfunction: Do not use if
ClCr < 25 ml/min
Monitoring:
 GI intolerance: Abdominal pain,
diarrhea, flatulence
 S/Sx hypoglycemia
 Should be taken with the first bite of
each meal for maximum effectiveness
Combination products
Glipizide and Metformin
(Metaglip)
Rosiglitazone and Metformin
(Avandamet)
Gylburide and Metformin
(Glucovance)
In general, these products offer little benefit over the individual agents and may actually be of higher cost to the patient. May
consider in patients that have been stable for sometime and may have compliance issues with multiple tablets. Would verify
insurance coverage or change in patient expense first.
Appendix A
Insulin Recommendations for Type 2 Diabetes Mellitus
Review of Insulin Preparations
Type of Insulin
Rapid Acting
Lispro (Humalog)
Aspart (NovoLog)
Short Acting
Regular
(Humulin R/Novolin R)
Intermediate Acting
Isophane insulin – NPH
(Humulin N/ Novolin N)
Insulin Zinc – Lente
(Humulin L/Novolin L)
Long Acting
Insulin Zinc Extended –
Ultralente (Humulin U)
Glargine (Lantus)
Premixed
Humulin 70/30
(70% NPH/30% Regular)
Humulin 50/50
(50% NPH/50% Regular
Humalog Mix 75/25
(75% NPL/25% Lispro)
Onset of
Action
Peak
Effective
Duration
Special Considerations
5-15 min
30-90 min
5 hrs
Patient should skip dose if meal
is going to be missed.
30-60 min
2-3 hrs
5-8 hrs
2-4 hrs
4-10 hrs
10-16 hrs
2-4 hrs
4-12 hrs
12-18 hrs
6-10 hrs
10-16 hrs
18-24 hrs
2-4 hrs
no peak
20-24 hrs
30-60 min
Mixed as
above
Mixed as
above
Mixed as
above
10-16 hrs
Mixed as
above
10-16 hrs
30-60 min
5-15 min
10-16 hrs
10-16 hrs
NPL – insulin lispro protamine
NovoLog Mix 70/30
(70% NP/30% aspart)
5-15 min
NP-protamine aspart
May use in patients who need
long acting insulin, but are
unwilling/unable to give
multiple injections as this
product can be mixed with other
insulins.
Cannot mix with other insulins
in same syringe or use same
syringe.
 Premixed insulins may be
suitable for patients who are
unwilling/unable to mix insulin
or give multiple injections.
 Patients must adhere to
constant diet and not skip meals.
 It should be recognized it may
be difficult to achieve tight
blood glucose control.
General guidelines for adjusting insulin doses
 Patients need to be properly educated on injection technique and insulin dose adjustments.
 Adjustments in basal insulin dosage should be made only if the increase in blood glucose pattern is not
caused by a temporary change in diet, exercise, stress, illness or other medications. These components
should be stable before alteration of basal insulin. Short-term adjustments in short or rapid acting
insulin may be made to cover this temporary change.
 Dose adjustment should be made in 1-2 unit increments unless patient has demonstrated little change in
blood glucose, then may change at 3-4 unit increments. Also, increments of 3-4 units may be used in
patients with blood glucose readings > 200 mg/dl. It should be understood that the degree of insulin
resistance varies in patients with Type 2 Diabetes and thus the response to 1 unit of insulin may vary
between patients.
 Insulin adjustments should focus on stabilization of fasting and pre-prandial blood glucose with basal
insulin first, and then focus on post-prandial blood sugar adjustment.
 Target one component to adjust at a time focusing on the highest blood glucose reading. If all readings
are elevated > 200mg/dl consider making alterations to all components and focusing on fasting readings.
Adjust:
Morning short or rapid acting insulin
Morning basal insulin or prelunch
short or rapid acting insulin
Predinner short or rapid acting
Predinner or bedtime basal insulin
Based on:
Prelunch blood glucose
Predinner blood glucose
Bedtime blood glucose
Morning (fasting) blood glucose
Initiation of Basal Insulin
Patient will need to SMBG 2-4 times daily
2. Start bedtime basal insulin dose of 10 units Glargine or NPH insulin
 Recommend to use glargine insulin as first line if blood glucose above goal for entire day and
NPH insulin if FBS high with good control of daytime blood glucose readings
3. Adjustment of basal insulin
 Assess fasting blood glucose every 3-4 days
 Increase basal insulin 1-2 units every 3-4 days until FBG goal of < 120mg/dl met or
hypoglycemia occurs (appropriate patients may be instructed to do this)
 May need to increase in increments of 2-4 units for FBG > 200mg/dl
4. Oral medication considerations
 Secretagogues - Do not need to discontinue at this time as blood glucose lowering effect may
remain on post-prandial readings. If post prandial blood glucose consistently elevated once FBG
is at goal may discontinue as patient may not be having benefit; assuming patient following proper
meal planning.
 Insulin Sensitizers – Continue as benefit to increasing receptor sensitivity to insulin.
Initiation of Bolus (Short-acting/Rapid Acting) Insulin
 On oral and/or basal insulin regimen
1. Patient should have stable dose of basal insulin with acceptable fasting blood glucose
readings.
2. Initiate rapid acting (lispro or aspart) or regular insulin prior to each meal. The rapid acting
insulins are preferable for patients that want more flexibility with timing of meals. Amount of
insulin based on post-prandial blood glucose as well as estimation of amount of carbohydrates
consumed with each meal.
3. Alternatively, a combination 70/30 product may be initiated for patients that are hesitant to
move to four injections a day or have difficulty drawing from multiple vials. The patient
needs to have a stable diet and consistent timing of meals to reduce the possibility of
hypoglycemia. Combination insulin is to be given 30 minutes before breakfast and dinner.
For patients on basal insulin, divide the dose in thirds and give 2/3 in before breakfast and 1/3
before dinner.
4. See general guidelines above for recommendations of insulin dose adjustments.
Initiation of Basal and Bolus Insulin
For patients not on oral anti-diabetic medications
1. Starting dose of insulin based on total daily dose of 0.2 to 0.5 units per kg as a starting range.
2. Once adequate spacing of meals is established, give 2/3 of total daily insulin dose at breakfast
and 1/3 before dinner; with 2/3 of each dose basal insulin and 1/3 bolus insulin. Some people
may require the total daily insulin dose to be given 50% in AM and 50% in PM.
3. Dosage adjustments should be made every 4-7 days based on fasting blood glucose first (See
general guidelines above for recommendations of insulin dose adjustments.)
Conversion of NPH or Ultralente to Glargine
 Initiate Glargine dose at 70-80% of NPH or Ultralente dose.
 Glargine insulin cannot be mixed with rapid or short acting insulins and a separate syringe must also be
used for administration.
Additional Bolus Insulin
 Patients may add 1 unit of rapid or short acting insulin for every 30-50 points over
150 mg/dl to their current bolus insulin dose.
Carbohydrate Counting
 Patients may be taught carbohydrate counting and coverage with bolus insulin.
 In general 1 unit of insulin will cover 10-15 grams of carbohydrate. Patients with Type 2 DM may
require 1 unit of insulin for 5 grams of carbohydrate. (Refer to Certified Diabetes Educator, Dietitian or
Pharmacy Diabetes Consult Service.)
Deanne Hall, PharmD 09/18/03