A Real-World Approach to Insulin Therapy in Primary Care Practice
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P R A C T I C A L P O I N T E R S
A Real-World Approach to Insulin Therapy
in Primary Care Practice
Irl B. Hirsch, MD; Richard M. Bergenstal, MD; Christopher G. Parkin, MS; Eugene Wright, Jr., MD; and John B. Buse, MD, PhD
Because of these factors, providers may However, subjects who had been inten-
T
ype 2 diabetes is a progressive
disease characterized by relent- delay in making the necessary transition sively treated during the DCCT showed
less deterioration of pancreatic - from oral agents to insulin. Indeed, significant decreases in risk for
cell function.1 With the increasing inci- recent evidence suggests that the hemo- nephropathy and retinopathy compared
dence of type 2 diabetes, especially globin A1c (A1C) result that triggers glu- with subjects from the conventional
among younger individuals who will cose-lowering action is ≥ 9%.3 This is treatment arm. In other words, the bene-
live longer with their disease, more unfortunate because numerous studies fits of 6.5 years of intensive treatment
patients will develop severe insulin defi- have shown that excellent glycemic con- during the DCCT have extended well
ciency and require insulin replacement. trol can be achieved with insulin therapy beyond the time of intensive therapy.
Because primary care providers see the in patients with type 2 diabetes.4–7
vast majority of patients with type 2 dia- Moreover, there is an increasing body of Insulin May Have a Protective
betes, they may soon find themselves evidence showing that early and effec- Quality
overwhelmed with insulin-requiring tive intervention with insulin is more Insulin therapy may actually protect
patients. important than had been previously against endothelial damage.
This article provides some practical believed.8–10 Observational and interventional evi-
guidelines for initiating insulin therapy dence consistently indicates that
in primary care practice. It is important Early and Aggressive Intervention glycemic control with insulin therapy in
to remember, however, that these are Matters the hospital setting can improve clinical
general guidelines and that management Insulin is considered the most effective outcomes.14–17 Malmberg et al.14 demon-
should be individualized for each treatment for lowering extremely high strated that the unfavorable long-term
patient. glucose. This is important because inhi- prognosis for myocardial infarction
bition of glucotoxicity may be beneficial could be improved by insulin treatment.
WHY INSULIN THERAPY? in preserving functional -cell mass.1 In that study, diabetic patients who
Some primary care providers may be Oral agents do not work as quickly or received insulin infusion immediately
apprehensive about using insulin in lower glucose enough to effectively within 24 hours of myocardial infarc-
patients with type 2 diabetes. Wallace address glucotoxicity in many patients. tion, followed by multidose subcuta-
and Matthews2 have gone so far as to For example, patients treated with sul- neous insulin treatment for at least 3
suggest that patients and providers have fonylureas show a decrease in fasting months, showed a significantly lower
often “colluded in implicit and unspoken glucose of only 60–70 mg/dl; the A1C mortality rate (19%) at 1 year compared
contracts to continue oral agents for as value will decrease by 1.5–2.0 percent- with subjects who received standard
long as possible.” age points.11,12 treatment (26%), which generally
Concerns about hypoglycemia and New data from the Epidemiology of included sulfonylurea therapy.
patient willingness and/or ability to Diabetes Interventions and Complica-
inject insulin are good reasons why tions (EDIC) study highlight the impor- New Insulin Analogs More Closely
many providers may approach insulin tance of early intervention to aggressive- Match Normal Physiology
therapy with caution. Compounding this ly lower glucose.8 The EDIC study is an New insulin analogs (rapid and long act-
reluctance is the perception that insulin ongoing effort that follows the cohort ing) closely match normal physiolo-
therapy is too complex to manage in a from the Diabetes Control and Compli- gy.18–20 Rapid-acting insulin analogs,
busy primary care practice; prescribing cations Trial (DCCT).13 In the EDIC such as insulin aspart and insulin lispro,
information provided by manufacturers study, glycemic levels no longer differed produce higher serum insulin levels ear-
has been somewhat vague regarding ini- substantially between the two original lier and have a shorter duration of action
tial dosing and titration. DCCT treatment groups at 7 years. than regular human insulin. This results
78 Volume 23, Number 2, 2005 • CLINICAL DIABETESP R A C T I C A L P O I N T E R S
in lower postprandial glucose excursions in patients with type 2 diabetes much should be put on insulin therapy, it is
and shorter durations of postprandial earlier and much more aggressively. helpful to look to the guidelines for
hyperglycemia, with significantly glycemic control. The American Dia-
reduced incidence of severe hypo- Patients Will Eventually Need Insulin betes Association (ADA)36 and American
glycemia in patients with type 2 dia- Therapy College of Endocrinology (ACE)37 pub-
betes.18,19 Additionally, studies that have As stated earlier, type 2 diabetes is a lish goals for A1C, postprandial glucose,
looked at the effects of rapid-acting progressive disease in which -cell and fasting/preprandial glucose (Table
insulin analogs combined with interme- function deteriorates. Findings from the 1). Most patients who are unable to
diate-acting insulins (free-mixed and U.K. Prospective Diabetes Study achieve these goals using oral agents are
premixed preparations) in patients with (UKPDS) showed that deterioration in candidates for insulin therapy. Table 2
type 2 diabetes have shown improved -cell function occurred in the diet-only lists the more commonly used insulins,
postprandial glucose control with treatment group as well as in patients along with information about their peak
reduced hypoglycemia.21–23 treated with sulfonylureas or metformin, activity.
suggesting that neither of these agents The key to making this determina-
New Evidence Links Glucose slowed the rate of decline.30 The tion is timely (preferably weekly) titra-
Excursions to Cardiovascular Risk UKPDS also showed that even basal tion of dosages until either glucose tar-
Reducing postprandial glucose excur- insulin (ultralente) did not slow -cell gets are met or maximum effective
sions is particularly important in light of deterioration.30 Another study found that dosages fail to achieve target levels. For
new data that show a relationship ~ 30% of patients initially treated with a example, weekly titration of sulfony-
between postprandial hyperglycemia and sulfonylurea drug have a poor response; lurea dosages, in combination with dai-
atherosclerotic risk. A recent study from the remaining 70% experience a failure ly fasting glucose data (provided by the
Esposito et al.10 demonstrated that rate of ~ 4–5% per year.31 It is, there- patient), will show whether monothera-
reduction of postprandial hyperglycemia fore, reasonable to conclude that most py with sulfonylurea can provide ade-
in patients with type 2 diabetes is asso- patients with type 2 diabetes will even- quate glycemic control. If not, the addi-
ciated with carotid intima-media thick- tually need exogenous insulin. tion and timely titration of a second
ness (CIMT) regression; CIMT is a clin- Unfortunately, insulin therapy too agent (metformin or a thiazolidine-
ical marker for atherosclerosis. Recent often is used as a “punishment” for dione) over the next 2 months, along
data from Ceriello et al.9 showed that above-target hyperglycemia. A better with continued blood glucose monitor-
postprandial hyperglycemia is accompa- approach would be to explain to patients ing, will show whether combination
nied by endothelial dysfunction in early in the course of their disease, oral therapy can provide adequate
patients with type 2 diabetes and that instead of at the end, the natural history glycemic control. If not, insulin therapy
rapid-acting insulin at mealtime of insulin deficiency in type 2 diabetes.2 is clearly warranted and should be
improved endothelial function. Earlier promptly initiated (Figure 1).
reports from Ceriello et al.24 suggest that WHO SHOULD BE STARTED ON Although it may be tempting to add
postprandial hyperglycemia and hyper- INSULIN? a third oral agent, clinicians must consid-
triglyceridemia induce endothelial dys- Initiating therapy with oral agents is a er the added cost and potential side
function through oxidative stress. Other reasonable approach to take with most effects associated with triple oral thera-
studies support the link between post- patients, the exception being patients py. A recent study by Schwartz et al.38
prandial glucose excursions and athero- with extreme hyperglycemia (fasting showed that a regimen of premixed
sclerotic risk.25–28 plasma glucose > 250 mg/dl).32 These insulin in combination with metformin
Chiasson et al.29 showed that patients require insulin, even basal-bolus was as effective as but much less expen-
addressing postprandial hyperglycemia insulin therapy, to lower glucose levels.
using an -glucosidase inhibitor actually Otherwise, starting with oral therapy can Table 1. Goals for Glycemic
delayed progression from impaired glu- be very effective, especially in patients Control
cose tolerance to type 2 diabetes and was with a short duration of diabetes and, ADA ACE
associated with a significant reduction in thus, relatively adequate -cell function. A1C (%)P R A C T I C A L P O I N T E R S
Table 2. Onset, Peak, and Duration of Insulins
Insulin* Onset Peak Effective duration
Rapid-acting 5–15 minutes 30–90 minutes < 5 hours
Aspart
Lispro
Short-acting 30–60 minutes 2–3 hours 5–8 hours
Regular
Intermediate (basal) 2–4 hours 4–10 hours 10–16 hours
NPH
Long-acting (basal) 2–4 hours† No peak 20–24 hours
Glargine
Premixed
75% NPL/25% lispro 5–15 minutes Dual 10–16 hours
70% APS/30% aspart 5–15 minutes Dual 10–16 hours
70% NPH/30% regular/NPH 30–60 minutes Dual 10–16 hours
*Assumes 0.1–0.2 units/kg/injection. Onset and duration may vary significantly by injection site.
†Time to steady state.
Adapted from DeWitt DE, Hirsch IB: Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA
289:2254–2264, 2003
and complexity out of initiating insulin
therapy in patients with type 2 diabetes.
Figure 1 provides an algorithm for tran-
sition from oral therapy to insulin.
Match the Regimen to the Patient
A basal-bolus regimen—glargine with
rapid-acting insulin analogs at each
meal—is the ideal regimen in terms of
physiological action and overall
glycemic control. However, many
patients are reluctant to start with a
basal-bolus insulin regimen.
Furthermore, basal-bolus insulin man-
agement requires not only motivation of
both patient and provider, but also com-
prehensive training in carbohydrate
counting (or some method of
food/insulin matching) and insulin
adjustment. Therefore, it is important to
match the insulin regimen to the individ-
ual needs, concerns, and capabilities of
each patient.
Figure 1. Algorithm for initiating insulin therapy. Patients who are reluctant to do
basal-bolus management initially often
sive than triple oral therapy; a high per- HOW TO START PATIENTS ON make the transition to multiple daily
centage of subjects (16.3%) from the INSULIN injection (MDI) regimens after gaining
triple oral agent treatment group did not Starting patients on insulin does not confidence in their ability to safely and
complete the regimen because of a lack have to be difficult. This section presents effectively use insulin through less inten-
of efficacy or side effects. an approach that takes the uncertainty sive regimens. Table 3 presents common
80 Volume 23, Number 2, 2005 • CLINICAL DIABETESP R A C T I C A L P O I N T E R S
Table 3. Patient-Based Insulin Regimens analog premixed insulin is an option if
the patient eats small lunches or misses
Basal-Only Insulin lunch regularly. Although no definitive
A1C: > 7.5–10% studies have looked at this issue, the
Medication: Oral medications adequately control postprandial glucose excursions authors agree that for individuals eating
Pattern: High fasting glucose with minimal glucose rise during the day large lunches (e.g., > 40% of their total
Diet history: Small, regular meals (large meals will result in postprandial hyper- daily calories), a better premix insulin
glycemia) would be 70% NPH/30% regular insulin.
Lifestyle: Reluctance to do MDI, requires oral agents The problem with this regimen, however,
Monitoring: Fasting
is that the lunchtime meal needs to be
Once- or Twice-Daily Premixed Insulin consumed at about the same time each
Rapid-Acting Analog/Intermediate-Acting day to avoid hypoglycemia.
A1C: > 7.5% Basal-bolus insulin therapy may be
Medication: Oral agent failure (maximum tolerated dosages, contraindications, cost required for patients with glucose toxici-
issues)
ty (fasting plasma glucose > 250
Pattern: Any fasting glucose; glucose rises during the day
mg/dl).42 Basal-bolus insulin therapy can
Diet History: Large suppers/small lunches
Lifestyle: Consistent daily routine, reluctance to do MDI be continued or modified after glucose
Monitoring: Fasting and presupper (if insulin is administered twice daily) returns to near-normal levels. Addition-
ally, basal-bolus insulin management
Regular/NPH
should be presented as the next option if
A1C: > 7.5%
patients are unable to achieve targets
Medication: Oral agent failure (maximum tolerated dosages, contraindications, cost
issues) with a premixed insulin regimen. This
Pattern: Any fasting glucose; glucose rises during the day will be the rule for patients with more
Diet history: Isocaloric meals or larger lunches severe insulin deficiency.
Lifestyle: Consistent daily routine, reluctance to do MDI
Monitoring: Fasting and presupper (if insulin is administered twice daily) Start Low and Titrate Steadily
Basal-Bolus (MDI) A common starting dose for insulin ther-
A1C: > 7.5% apy in patients with type 2 diabetes is
Pattern: Regimen can be matched to any pattern to achieve glycemic control 0.15 units/kg body wt/day;42 however,
Diet history: Regimen can be matched to any diet to achieve glycemic control because > 90% of patients with type 2
Lifestyle: Erratic schedule, motivated to achieve tight glycemic control diabetes are insulin resistant,43 signifi-
Monitoring: Frequent blood glucose monitoring (minimum before meals and bedtime) cantly higher doses are often required to
achieve glycemic targets.39-41,44
insulin regimens based on patient clini- daily premixed therapy. In one study, The Treat-to-Target study44 used a
cal status and lifestyle characteristics. there was a slight increase in overall starting dose of 10 units/day with
Although regimens for once-daily hypoglycemia with no increase in noc- glargine or human NPH at bedtime;
glargine and once-daily and twice-dai- turnal hypoglycemia,39 whereas another mean daily dosages at end point adjusted
ly premixed insulin are listed, it is study showed no difference in overall for body weight were 0.48 units/kg for
important to note that recent studies hypoglycemia with less nocturnal hypo- glargine and 0.42 units/kg for NPH in
comparing once-daily regimens to glycemia in the premix group.40 A third those patients who were maintained on
twice-daily regimens have demonstrat- study showed similar findings regarding one or two oral agents throughout the
ed significant differences between the overall hypoglycemia.41 In short, no study. This is equivalent to ~ 40
two approaches.39–41 definitive differences in hypoglycemia units/day in an average 200-lb patient. A
One study showed that twice-daily were consistently seen in these studies. study of premixed insulin in patients on
premixed insulin (25% lispro/75% NPL) When postprandial glucose is not oral agents initiated insulin therapy with
provided lower A1C levels compared adequately controlled by combination a dose of 6 units/day; however, the aver-
with once-daily glargine when patients therapy using basal insulin and oral age dosage at 28 weeks was > 75
were randomized to one or the other agents, a twice-daily regimen using a units/day (0.85 units/kg/day), with no
insulin regimen in addition to existing premixed insulin preparation (prebreak- major hypoglycemic episodes reported.41
metformin therapy39 Results also showed fast, presupper) is preferred. Clinicians The differences in average dosages
a smaller rise in postprandial glucose can start patients on once-daily injec- at end point reported in these studies
levels and a higher proportion of patients tions at the evening meal and add the resulted from differences in baseline
achieving an A1C of ≤ 7.0% on twice- second injection as needed. Rapid-acting A1C levels, durations of diabetes, and
CLINICAL DIABETES • Volume 23, Number 2, 2005 81P R A C T I C A L P O I N T E R S
overall levels of insulin resistance in the persist for months (or years, in some cas- ticularly those who are self-adjusting
study subjects. Nevertheless, these stud- es). A major obstacle to timely insulin their insulin dosages.
ies show 10 units/injection to be a safe adjustment is primarily the logistics of If patients are not at goal after 3–6
starting dose for once-daily and twice- communicating with the patient. Table 6 months of therapy or if recurrent hypo-
daily insulin regimens (Table 4). presents some options for patient follow- glycemia limits titration, consider chang-
It is important to note that although up that may expedite achieving glycemic ing the regimen. Table 7 presents strate-
glargine can be taken at any time during targets on timely basis. Diabetes educa- gies for making this transition.
the day, it should be injected at the same tion is a crucial aspect of patient care When assessing the need to change
time every day. Patients should docu- and is recommended for all patients, par- regimens, it is important to understand
ment all results from self-monitoring of
blood glucose (SMBG) and insulin dos- Table 4. Starting Dosages
es in their logbooks when starting or
1 Premix 10 units (presupper)
adjusting insulin. Glucose meter down-
2 Premix 10 units (prebreakfast), 10 units (presupper)
loading is another excellent tool for 1 Basal 10 units (bedtime)
review of SMBG data.45 MDI Individualized*
Monitor and Adjust Therapy Until *Patients with type 2 diabetes seldom start insulin on an MDI regimen. Dosages should be
based on the current insulin regimen. Additionally, consider referral to a certified diabetes
Targets are Achieved
education program for training in carbohydrate counting and insulin adjustment.
Although insulin is the most effective
treatment for lowering glucose, a recent
national study showed that only half of Table 5. Dosage Titration for Once-Daily or Twice-Daily Insulin Regimens
patients with type 2 diabetes who are
treated with insulin achieve an A1C Most Values (during last 3–7 days) Dosage Change
< 7%.46 To be successful, insulin therapy < 80 mg/dl –2 units
requires timely and appropriate titration 80–109 mg/dl No change
of dosages. Table 5 presents a titration 110–139 mg/dl +2 units
140–179 mg/dl +4 units
schedule that can be used with once-
≥ 180 mg/dl +6 units
daily and twice-daily regimens to make
safe and timely insulin adjustments. Adjust prebreakfast dose based on presupper/evening value.
Working with this schedule, patients Adjust presupper (premixed)/bedtime (basal) dose based on prebreakfast/morning value.
measure blood glucose once or twice DO NOT increase dose if hypoglycemia (< 70 mg/dl) or symptoms are present.
daily (prebreakfast, presupper) depend-
ing on their regimen. Based on these Table 6. Options for Patient Follow-Up
blood glucose data reported by the
patient, the clinician can then make step- 1. Patient visit
wise adjustments in response to the aver- • First month: Patient visits physician once per week.
age glucose values. Prebreakfast dosage • Thereafter until glycemic targets are achieved: Patient visits physician or sends blood
adjustments are based on presupper glu- glucose monitoring data weekly to physician via phone, fax, or e-mail. Physician/nurse
responds with instructions for dosage adjustment.
cose results, whereas presupper dosage
adjustments are based on prebreakfast 2. Phone, fax, e-mail
glucose values. • First month: Patient sends blood glucose monitoring data weekly to physician via
For example, in a patient on 10 units phone, fax, or e-mail. Physician/nurse responds with instructions for dosage adjust-
of premixed insulin twice daily who ment.
reports prebreakfast glucose values rang- • Thereafter until glycemic targets are achieved: Patient continues to send blood glucose
monitoring data weekly. Physician/nurse (by protocol) responds with instructions for
ing from 148 to 175 mg/dl over the past
dosage adjustment.
3–7 days, the appropriate adjustment
would be an additional 4 units of insulin 3. Patient self-adjustment
before supper. • First month: Patient monitors blood glucose, adjusts insulin dosage as needed, and
Another key aspect of insulin titra- sends monitoring and dosage adjustment data weekly to physician via phone, fax, or e-
tion is timely adjustment. As with oral mail. Physician/nurse (by protocol) responds with instructions for dosage adjustment.
• Thereafter until glycemic targets are achieved: Patient continues to send blood glucose
therapy, clinicians often wait too long to
monitoring and insulin adjustment data to physician weekly. Physician/nurse (by pro-
make adjustments in insulin dosages,
tocol) responds with instructions for dosage adjustment.
allowing excessive glycemic exposure to
82 Volume 23, Number 2, 2005 • CLINICAL DIABETESP R A C T I C A L P O I N T E R S
Table 7. Transition From One Regimen to Another issue. Figure 3A illustrates how address-
ing fasting glucose can initially lower
Current 1 Basal → New 2 Premix fasting levels and even improve post-
• Divide total daily dose in half. Give prebreakfast and presupper premix insulin. The new prandial excursions by reducing gluco-
regimen should be started 18–24 hours after last basal dose was given. toxicity and thus improving -cell func-
• Titrate to goal based on SMBG data and diet history. The largest meal requires a larger tion. However, once fasting glucose
proportion of insulin. levels are normalized, increasing the
• Reduce total dose by 20% if there is recurrent hypoglycemia. basal dosage will not adequately address
Current 1 Premix → New 2 Premix the remaining postprandial hyper-
• Divide total daily dose in half. Give prebreakfast and presupper. glycemia (Figure 3B). Therefore, a regi-
• Titrate to goal based on SMBG data and diet history. The largest meal requires a larger men that addresses both fasting and post-
proportion of insulin. prandial hyperglycemia is needed
• Reduce total dose by 20% if there is recurrent hypoglycemia. (Figure 3C).
Current 1 Basal Only → Add Rapid-Acting Insulin at Largest Meal*
• Give 10% of total daily dose as rapid-acting analog at largest meal. CONCLUSION
• Reduce basal dose by 10%. Insulin therapy in the treatment of type
2 diabetes offers significant advantages
Current 2 Premix → MDI†
in efficacy and outcomes. However,
• Divide total daily dose in half.
unfounded fear of hypoglycemia and
• Initial basal insulin dose = total daily dose/2 80%.
• Initial prandial insulin dose = half of total daily dose percentage of estimated calories uncertainties regarding initial dosage
for each meal and titration have been key obstacles for
many providers when making the deci-
* This regimen serves as a transition to MDI therapy. sion to initiate insulin treatment in their
†
Example: Patient is currently on 60 units total daily dose of premix insulin (30 units twice
patients with type 2 diabetes.
daily) and eats ~ 20% of total daily calories at breakfast, 20% at lunch, and 60% at supper.
Given the progressive nature and
The new regimen would be 24 units of basal insulin with 6 units of rapid-acting insulin at
breakfast, 6 units at lunch, and 18 units at supper. increasing incidence of type 2 diabetes,
more patients will be faced with severe
and consider the impact of fasting glu- insulin deficiencies in their lifetimes. It
cose and postprandial glucose on overall is hoped that the information and recom-
glycemic control. Monnier et al.47
recently published findings that showed
a variable relationship between fasting
and glucose based on current A1C lev-
els. As shown in Figure 2, the report
revealed that the relative contribution of
fasting glucose to overall glycemia is
~ 70% in patients with an A1C of
> 10.2%; the contribution of fasting glu-
cose decreases as A1C levels decrease.
Knowing the relative contribution of
fasting and postprandial glucose to A1C
allows clinicians to make more informed
decisions about therapy. For example, if
a patient’s A1C is at 7.5%, adjustment
should focus on lowering postprandial
glucose; adding basal insulin will not
directly address postprandial hyper-
glycemia. Although the addition of basal
insulin will improve the overall A1C, as
shown in the Treat-to-Target study,44 it
will not lower the degree of postprandial
Figure 2. Relative contribution of fasting and postprandial glucose to A1C.
excursions. Only meal plan modification
Adapted from Monnier et al.47
or prandial insulin will address this
CLINICAL DIABETES • Volume 23, Number 2, 2005 83P R A C T I C A L P O I N T E R S
mendations provided in this article will
help primary care providers become
more effective in their management of
patients with type 2 diabetes.
ACKNOWLEDGMENTS
The authors gratefully acknowledge
support from Eli Lilly in funding the
expenses related to developing this
article.
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D, Ferdinande P, Lauwers P, Bouillon R: Inten- ty. Diabetologia 42:1050–1054, 1999 cian 70:489–500, 2004
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Engl J Med 345:1359–1367, 2001 Balkau B, Shipley M, Jarrett RJ, Pyorala K, Haffner SM, D’Agostino R Jr, Mykkanen L,
16
Pyorala M, Forhan A, Eschwege E: High blood Tracy R, Howard B, Rewers M, Selby J, Savage
Furnary AP, Zerr KJ, Grunkemeier GL, glucose concentration is a risk factor for mortali- PJ, Saad MF: Insulin sensitivity in subjects with
Starr A: Continuous intravenous insulin infusion ty in middle-aged non-diabetic men. Diabetes type 2 diabetes: relationship to cardiovascular
reduces the incidence of deep sternal wound Care 21:360–367, 1998 risk factors: the Insulin Resistance Atherosclero-
infection in diabetic patients after cardiac surgical sis Study. Diabetes Care 22:562–568, 1999
29
procedures. Ann Thorac Surg 67:352–360, [dis- Chiasson JL, Josse RG, Gomis R, Hanefeld
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cussion 360–362], 1999 M, Karasik A, Laakso M, the STOP-NIDDM Riddle MC, Rosenstock J, Gerich J, the
17
Trail Research Group: Acarbose for prevention of Insulin Glargine 4002 Study Investigators: The
Lazar HL, Chipkin SR, Fitzgerald CA, Bao type 2 diabetes mellitus: the STOP-NIDDM ran- Treat-to-Target Trial: randomized addition of
Y, Cabral H, Apstein CS: Tight glycemic control domised trial. Lancet 359:2072–2077, 2002 glargine or human NPH insulin to oral therapy of
in diabetic coronary artery bypass graft patients type 2 diabetic patients. Diabetes Care
30
improves perioperative outcomes and decreases Turner RC, Cull CA, Frighi V, Holman RR: 26:3080–3086, 2003
recurrent ischemic events. Circulation Glycemic control with diet, sulfonylurea, met-
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109:1497–1502, 2004 formin, or insulin in patients with type 2 diabetes Hirsch IB: Blood glucose monitoring tech-
18
mellitus: progressive requirement for multiple nology: translating data into practice. Endocr
Rosenfalck AM, Thorsby P, Kjems L, Birke- therapies (UKPDS 49). JAMA 281:2005–2012, Pract 10:67–76, 2004
land K, Dejgaard A, Hanssen KF, Madsbad S: 1999 46
Improved postprandial glycaemic control with Koro CE, Bowlin SJ, Bourgeois N, Fedder
31
insulin aspart in type 2 diabetic patients treated Groop LC: Sulfonylureas in NIDDM. Dia- DO: Glycemic control from 1988 to 2000 among
with insulin. Acta Diabetol 37:41–46, 2000 betes Care 15:737–754, 1992 U.S. adults diagnosed with type 2 diabetes: a pre-
19 32
liminary report. Diabetes Care 27:17–20, 2004
Anderson JH Jr, Brunelle RL, Keohane P, DeFronzo RA: Pharmacologic therapy for
47
Koivisto VA, Trautmann ME, Vignati L, type 2 diabetes mellitus. Ann Intern Med Monnier L, Lapinski H, Colette C: Contri-
DiMarchi R: Mealtime treatment with insulin 131:281–303, 1999 butions of fasting and postprandial plasma glu-
analog improves postprandial hyperglycemia and 33
cose increments to the overall diurnal hyper-
hypoglycemia in patients with non-insulin- Nathan DM: Initial management of glycemia of type 2 diabetic patients: variations
dependent diabetes mellitus. Arch Intern Med glycemia in type 2 diabetes mellitus. N Engl J with increasing levels of HbA1c. Diabetes Care
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Rosenstock J, Schwartz SL, Clark CM Jr, Hayward RA, Manning WG, Kaplan SH,
Park GD, Donley DW, Edwards MB: Basal Wagner EH, Greenfield S: Starting insulin thera-
insulin therapy in type 2 diabetes: 28-week com- py in patients with type 2 diabetes: effectiveness,
complications, and resource utilization. JAMA Irl B. Hirsch, MD, is a professor of med-
parison of insulin glargine (HOE 901) and NPH
insulin. Diabetes Care 24:631–636, 2001 278:1663–1669, 1997 icine in the Division of Metabolism,
21
Jacobon L, Sogaard B, Riis A: Pharmacoki-
35
UKPDS Study Group: UKPDS 28: a ran- Endocrinology, and Nutrition at the Uni-
netics and pharmacodynamics of a premixed for- domized trial of efficacy of early addition of met- versity of Washington Medical Center in
mulation of soluble and protamine-retarded formin in sulfonylurea-treated type 2 diabetes.
insulin aspart. Eur J Clin Pharmacol 56:399–403, Diabetes Care 21:87–92, 1998 Seattle. Richard M. Bergenstal, MD, is
2000 36
American Diabetes Association: Standards executive director of the International
22
Roach P, Trautmann ME, Anderson JH, the of medical care in diabetes. Diabetes Care 28 Diabetes Center and a clinical professor
Mix25 Study Group: Improved postprandial (Suppl. 1):S4–S36, 2005 at the University of Minnesota, both in
glycemia during treatment with an intermediate- 37
American Association of Clinical Endocri- Minneapolis. Christopher G. Parkin,
acting insulin mixture, Mix25 (Abstract). Dia- nologists: Medical guidelines for the manage-
betologia 41 (Suppl. 1):A244, 1998 MS, is a medical writer and consultant
ment of diabetes mellitus. Endocr Pract 8 (Suppl.
23
Roach P, Trautmann M, Arora V, Sun B, 1):40–82, 2002 to professional medical organizations
Anderson JH Jr, and the Mix50 Study Group:
Improved postprandial blood glucose control and
38
Schwartz S, Sievers R, Strange P, Lyness and healthcare companies and president
WH, Hollander P: Insulin 70/30 mix plus met-
reduced nocturnal hypoglycemia during treatment formin versus triple oral therapy in the treatment of CGParkin Communications in
with two novel insulin lispro-protamine formula-
tions, insulin lispro mix25 and insulin lispro of type 2 diabetes after failure of two oral drugs: Carmel, Ind., Eugene E. Wright, Jr., MD,
efficacy, safety, and cost analysis. Diabetes Care
mix50. Clin Ther 21:523–534, 1999 26:2238–2243, 2003 is medical director of Primary Care and
CLINICAL DIABETES • Volume 23, Number 2, 2005 85P R A C T I C A L P O I N T E R S
Specialty Practices of Cape Fear Valley support from Mannkind Corporation. Pharmaceuticals.
Health System in Fayetteville, N.C. John Dr. Bergenstal has served on advi- The University of North Carolina
B. Buse, MD, PhD, is an associate pro- sory panels for, received consulting fees has received honoraria related to Dr.
fessor at the University of North Caroli- or honoraria from, and received Buse’s speaking engagements for Abbott,
na School of Medicine in Chapel Hill, research support from Eli Lilly, Novo Pfizer, and Eli Lilly; grant support relat-
where he is the division chief of General Nordisk, and Sanofi-Aventis Pharma- ed to his research activities from Bristol-
Medicine and director of the Diabetes ceuticals. Myers Squibb, Novartis Pharmaceuti-
Care Center. He is also an associate edi- Mr. Parkin has received consulting cals, and Pfizer; and consulting fees
tor of Clinical Diabetes. fees from Abbott Diabetes Care, Bayer related to his formal advisory activities
Diagnostics, Eli Lilly, EMD Pharma- from Amylin Pharmaceuticals, BD
Notes of disclosure: Dr. Hirsch has ceuticals, Roche Diagnostics, and Research Laboratories, Eli Lilly, Merck,
received consulting fees or honoraria for Sanofi-Aventis Pharmaceuticals. and Bristol-Myers Squibb.
speaking engagements from Eli Lilly, Dr. Wright has served on advisory All of these companies manufacture
Novo Nordisk, and Sanofi-Aventis Phar- panels and received consulting fees or pharmaceutical products for the treat-
maceuticals. He also receives research honoraria from Eli Lilly and Amylin ment of diabetes.
86 Volume 23, Number 2, 2005 • CLINICAL DIABETESYou can also read
