Glycemic Management in Type 2 Diabetes 1. AACE Comprehensive Care Plan Disease management from a...
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Glycemic Management in Type 2 Diabetes 1. AACE Comprehensive Care Plan Disease management from a multidisciplinary team Antihyperglycemic pharmacotherapy
AACE Comprehensive Care Plan Disease management from a
multidisciplinary team Antihyperglycemic pharmacotherapy
Comprehensive diabetes self-education for the patient Therapeutic
lifestyle change Comprehensive Care Plan 2 Handelsman Y, et al.
Endocr Pract. 2011;17(suppl 2):1-53.
Slide 3
Glycemic Management in Type 2 Diabetes Therapeutic Lifestyle
Change 3
Slide 4
Components of Therapeutic Lifestyle Change Healthful eating
Sufficient physical activity Sufficient sleep Avoidance of tobacco
products Limited alcohol consumption Stress reduction 4 Handelsman
Y, et al. Endocr Pract. 2011;17(suppl 2):1-53.
Slide 5
AACE Healthful Eating Recommendations 5 Handelsman Y, et al.
Endocr Pract. 2011;17(suppl 2):1-53. TopicRecommendation General
eating habits Regular meals and snacks; avoid fasting to lose
weight Plant-based diet (high in fiber, low calories, low glycemic
index, high in phytochemicals/antioxidants) Understand Nutrition
Facts Label information Incorporate beliefs and culture into
discussions Informal physician-patient discussions Use mild cooking
techniques instead of high-heat cooking Carbohydrate Understand
health effects of the 3 types of carbohydrates: sugars, starch, and
fiber Target 7-10 servings per day of healthful carbohydrates
(fresh fruits and vegetables, pulses, whole grains) Lower-glycemic
index foods may facilitate glycemic control:* multigrain bread,
pumpernickel bread, whole oats, legumes, apple, lentils, chickpeas,
mango, yams, brown rice Fat Eat healthful fats:
low-mercury/low-contaminant-containing nuts, avocado, certain plant
oils, fish Limit saturated fats (butter, fatty red meats, tropical
plant oils, fast foods) and trans fats Use no- or low-fat dairy
products Protein Consume protein from foods low in saturated fats
(fish, egg whites, beans) Avoid or limit processed meats
Micronutrients Routine supplementation not necessary except for
patients at risk of insufficiency or deficiency Chromium; vanadium;
magnesium; vitamins A, C, and E; and CoQ10 not recommended for
glycemic control *Insufficient evidence to support a formal
recommendation to educate patients that sugars have both positive
and negative health effects
Slide 6
AACE Medical Nutritional Therapy Recommendations Consistency in
day-to-day carbohydrate intake Adjusting insulin doses to match
carbohydrate intake (eg, use of carbohydrate counting) Limitation
of sucrose-containing or high- glycemic index foods Adequate
protein intake Heart-healthy diets Weight management Exercise
Increased glucose monitoring 6 Handelsman Y, et al. Endocr Pract.
2011;17(suppl 2):1-53.
Slide 7
150 minutes per week of moderate-intensity exercise Flexibility
and strength training Aerobic exercise (eg, brisk walking) Start
slowly and build up gradually Evaluate for contraindications and/or
limitations to increased physical activity before patient begins or
intensifies exercise program Develop exercise recommendations
according to individual goals and limitations AACE Physical
Activity Recommendations 7 Handelsman Y, et al. Endocr Pract.
2011;17(suppl 2):1-53.
Slide 8
Glycemic Management in Type 2 Diabetes Antihyperglycemic
Therapy 8
Slide 9
Noninsulin Agents Available for Treatment of Type 2 Diabetes
ClassPrimary Mechanism of ActionAgentAvailable as -Glucosidase
inhibitors Delay carbohydrate absorption from intestine
AcarbosePrecose or generic MiglitolGlyset Amylin analogue Decrease
glucagon secretion Slow gastric emptying Increase satiety
PramlintideSymlin Biguanide Decrease HGP Increase glucose uptake in
muscle MetforminGlucophage or generic Bile acid sequestrant
Decrease HGP? Increase incretin levels? ColesevelamWelChol DPP-4
inhibitors Increase glucose-dependent insulin secretion Decrease
glucagon secretion AlogliptinNesina LinagliptinTradjenta
SaxagliptinOnglyza SitagliptinJanuvia Dopamine-2 agonist Activates
dopaminergic receptors BromocriptineCycloset 9 HGP, hepatic glucose
production. Inzucchi SE, et al. Diabetes Care.
2012;35:1364-1379.
Slide 10
Noninsulin Agents Available for Treatment of Type 2 Diabetes
ClassPrimary Mechanism of ActionAgentAvailable as Glinides Increase
insulin secretion NateglinideStarlix or generic RepaglinidePrandin
GLP-1 receptor agonists Increase glucose-dependent insulin
secretion Decrease glucagon secretion Slow gastric emptying
Increase satiety ExenatideByetta Exenatide XRBydureon
LiraglutideVictoza Sulfonylureas Increase insulin secretion
GlimepirideAmaryl or generic GlipizideGlucotrol or generic
Glyburide Dia eta, Glynase, Micronase, or generic
Thiazolidinediones Increase glucose uptake in muscle and fat
Decrease HGP PioglitazoneActos Rosiglitazone*Avandia *Use
restricted due to increased risk of myocardial infarction (MI) 10
HGP, hepatic glucose production. Inzucchi SE, et al. Diabetes Care.
2012;35:1364-1379.
Slide 11
Insulins Available for the Treatment of Type 2 Diabetes
ClassPrimary Mechanism of ActionAgentAvailable as Basal Increase
glucose uptake Decrease HGP DetemirLevemir GlargineLantus Neutral
protamine Hagedorn (NPH) Generic Prandial AspartNovoLog
GlulisineApidra LisproHumalog Regular humanHumulin, generic
Premixed Biphasic aspartNovoLog Mix Biphasic lisproHumalog Mix 11
Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.
Slide 12
Pharmacokinetics of Insulin 12 AgentOnset (h)Peak (h)Duration
(h)Considerations Basal NPH2-44-1010-16Greater risk of nocturnal
hypoglycemia compared to insulin analogues Glargine~1-4No
pronounced peak* Up to 24 hours Less nocturnal hypoglycemia
compared to NPH Detemir Prandial Regular~0.5-1~2-3Up to 8 Must be
injected 30-45 min before a meal Injection with or after a meal
could increase risk for hypoglycemia Aspart
Stratify treatment based on initial A1C level Initial
monotherapy for A1C 6.5% to 7.5% Initial dual therapy for A1C 7.6%
to 9.0% Initial triple therapy or insulin for A1C >9.0% Monitor
A1C carefully and intensify therapy at 2- to 3- month intervals if
A1C goal not achieved Monotherapy dual therapy Dual therapy triple
therapy or insulin oral agents Combine agents with different
mechanisms of action Overview of AACE/ACE T2DM Algorithm Rodbard
HW, et al. Endocr Pract. 2009;15:540-559 16
Slide 17
*The abbreviations used here correspond to those used on the
algorithm (Fig. 1). **The term glinide includes both repaglinide
and nateglinide. Benefits are classified according to major effects
on fasting glucose, postprandial glucose, and nonalcoholic fatty
liver disease (NAFLD). Eight broad categories of risks are
summarized. The intensity of the background shading of the cells
reflects relative importance of the benefit or risk.* Available at
www.aace.com/pub AACE December 2009 Update. May not be reproduced
in any form without express written permission from AACE 17
Slide 18
A1C 6.5 7.5% ** Monotherapy MET + GLP-1 or DPP4 1 TZD 2 Glinide
or SU 5 TZD + GLP-1 or DPP4 1 MET + Colesevelam AGI 3 2 - 3 Mos.
*** Dual Therapy MET + GLP-1 or DPP4 1 + TZD 2 Glinide or SU 4,7
A1C > 9.0% No Symptoms Drug Naive Under Treatment INSULIN Other
Agent(s) 6 Symptoms INSULIN Other Agent(s) 6 INSULIN Other Agent(s)
6 Triple Therapy AACE/ACE Algorithm for Glycemic Control Committee
Cochairpersons: Helena W. Rodbard, MD, FACP, MACE Paul S.
Jellinger, MD, MACE Zachary T. Bloomgarden, MD, FACE Jaime A.
Davidson, MD, FACP, MACE Daniel Einhorn, MD, FACP, FACE Alan J.
Garber, MD, PhD, FACE James R. Gavin III, MD, PhD George
Grunberger, MD, FACP, FACE Yehuda Handelsman, MD, FACP, FACE Edward
S. Horton, MD, FACE Harold Lebovitz, MD, FACE Philip Levy, MD, MACE
Etie S. Moghissi, MD, FACP, FACE Stanley S. Schwartz, MD, FACE *
May not be appropriate for all patients ** For patients with
diabetes and A1C < 6.5%, pharmacologic Rx may be considered ***
If A1C goal not achieved safely Preferred initial agent 1DPP4 if
PPG and FPG or GLP-1 if PPG 2TZD if metabolic syndrome and/or
nonalcoholic fatty liver disease (NAFLD) 3AGI if PPG 4Glinide if
PPG or SU if FPG 5Low-dose secretagogue recommended 6a)Discontinue
insulin secretagogue with multidose insulin b)Can use pramlintide
with prandial insulin 7Decrease secretagogue by 50% when added to
GLP-1 or DPP-4 8If A1C < 8.5%, combination Rx with agents that
cause hypoglycemia should be used with caution 9If A1C > 8.5%,
in patients on Dual Therapy, insulin should be considered MET +
GLP-1 or DPP4 1 SU 7 TZD 2 GLP-1 or DPP4 1 TZD 2 A1C 7.6 9.0% Dual
Therapy 8 2 - 3 Mos. *** Triple Therapy 9 INSULIN Other Agent(s) 6
MET + GLP-1 or DPP4 1 or TZD 2 SU or Glinide 4,5 MET + GLP-1 or
DPP4 1 + TZD 2 GLP-1 or DPP4 1 + SU 7 TZD 2 MET DPP4 1 GLP-1TZD 2
AGI 3 Available at www.aace.com/pub AACE December 2009 Update. May
not be reproduced in any form without express written permission
from AACE 18
Slide 19
A1C 6.5 7.5% ** Monotherapy MET+ GLP-1 or DPP4 1 TZD 2 Glinide
or SU 5 TZD+GLP-1 or DPP4 1 MET+ Colesevelam AGI 3 2 - 3 Mos. ***
Dual Therapy MET + GLP-1 or DPP4 1 + TZD 2 Glinide or SU 4,7
INSULIN Other Agent(s) 6 Triple Therapy MET DPP4 1 GLP-1TZD 2 AGI 3
2 - 3 Mos. *** *** If A1C goal not achieved safely Preferred
initial agent 1DPP4 if PPG and FPG or GLP-1 if PPG 2TZD if
metabolic syndrome and/or nonalcoholic fatty liver disease (NAFLD)
3AGI if PPG 4Glinide if PPG or SU if FPG 5Low-dose secretagogue
recommended 6a)Discontinue insulin secretagogue with multidose
insulin b)Can use pramlintide with prandial insulin 7Decrease
secretagogue by 50% when added to GLP-1 or DPP-4 Available at
www.aace.com/pub AACE December 2009 Update. May not be reproduced
in any form without express written permission from AACE LIFESTYLE
MODIFICATION AACE/ACE DIABETES ALGORITHM FOR GLYCEMIC CONTROL
19
Slide 20
MET+ GLP-1 or DPP4 1 + TZD 2 GLP-1 or DPP4 1 + SU 7 TZD 2 A1C
7.6 9.0% Available at www.aace.com/pub AACE December 2009 Update.
May not be reproduced in any form without express written
permission from AACE Dual Therapy 8 MET+ GLP-1 or DPP4 1 or TZD 2
SU or Glinide 4,5 2 - 3 Mos. *** Triple Therapy 9 2 - 3 Mos. ***
INSULIN Other Agent(s) 6 *** If A1C goal not achieved safely
Preferred initial agent 1DPP4 if PPG and FPG or GLP-1 if PPG 2TZD
if metabolic syndrome and/or nonalcoholic fatty liver disease
(NAFLD) 4Glinide if PPG or SU if FPG 5Low-dose secretagogue
recommended 6a)Discontinue insulin secretagogue with multidose
insulin b)Can use pramlintide with prandial insulin 7Decrease
secretagogue by 50% when added to GLP-1 or DPP-4 8If A1C < 8.5%,
combination Rx with agents that cause hypoglycemia should be used
with caution 9 If A1C > 8.5%, in patients on Dual Therapy,
insulin should be considered LIFESTYLE MODIFICATION AACE/ACE
DIABETES ALGORITHM FOR GLYCEMIC CONTROL 20
Slide 21
No Symptoms Drug Naive Under Treatment Symptoms MET+ GLP-1 or
DPP4 1 SU 7 TZD 2 GLP-1 or DPP4 1 TZD 2 A1C > 9.0% Available at
www.aace.com/pub AACE December 2009 Update. May not be reproduced
in any form without express written permission from AACE INSULIN
Other Agent(s) 6 INSULIN Other Agent(s) 6 1DPP4 if PPG and FPG or
GLP-1 if PPG 2TZD if metabolic syndrome and/or nonalcoholic fatty
liver disease (NAFLD) 6a)Discontinue insulin secretagogue with
multidose insulin b)Can use pramlintide with prandial insulin
7Decrease secretagogue by 50% when added to GLP-1 or DPP-4
LIFESTYLE MODIFICATION AACE/ACE DIABETES ALGORITHM FOR GLYCEMIC
CONTROL 21
Slide 22
Basal Insulin Therapy in T2DM: AACE/ACE Recommendations
Initiate insulin treatment by adding a long-acting basal
formulation to existing noninsulin agents 22 Relatively peakless
time-action curves Greater day- to-day consistency Lower risk of
hypoglycemia Start with 10 U or 0.1-0.2 U/kg per day at bedtime
Slowly titrate by 1-3 U every 2-3 days until FPG reaches the
desired target (
Slide 23
Prandial Insulin Therapy in T2DM: AACE/ACE Recommendations Add
prandial insulin when A1C levels remain high despite optimal
control of FPG with basal insulin noninsulin agents Basal-bolus
insulin therapy is flexible and is recommended for intensive
insulin therapy Premixed insulin analogues Consider for patients
with adherence problems Lack dosage flexibility and may increase
risk of hypoglycemia 23 Rodbard HW, et al. Endocr Pract.
2009;15:540-559. Faster onset of action Faster offset of action
Lower risk of hypoglycemia Rapid-acting insulin analogues are
preferred over regular human insulin
Slide 24
Early Insulin Use in Type 2 Diabetes Offers No Benefits Over
Standard Approaches 24 ORIGIN Trial Investigators. N Engl J Med.
2012;367:319-328. Outcome Reduction With an Initial Glargine
Intervention CV risk factors + prediabetes or T2DM (N=12,537)
Outcome Reduction With an Initial Glargine Intervention CV risk
factors + prediabetes or T2DM (N=12,537)
Slide 25
Metformin is the preferred initial agent for most patients
DPP-4 inhibitors are preferred if both PPG and FPG are elevated
GLP-1 agonists are preferred if the principal problem is elevated
PPG TZDs can be used to treat patients with metabolic syndrome
and/or nonalcoholic fatty liver disease (NAFLD) AGIs are useful for
treatment of elevated PPG Glinides can be useful for treatment of
elevated PPG SUs may be useful if major problem is elevated FPG
Colesevelam may be useful for patients near A1C goal but needing
additional LDL-C control AACE/ACE T2DM Algorithm: Special
Considerations and Caveats Rodbard HW, et al. Endocr Pract.
2009;15:540-559. 25
Slide 26
A1C goal 6.5% may not be appropriate for all patients For
patients with diabetes and A1C