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AACE Diabetes Algorithm
• Guide therapy based on A1C level– Focus on lifestyle intensification at all levels
• Important tenets:
– Target A1C is ≤6.5%• For patients without concurrent serious illness and at low hypoglycemic risk
• Based on associated lower risk of micro- and macrovascular complications
• Recommend monitoring A1C quarterly, along with fasting and postprandial blood glucose, with intensification of therapy until goal A1C is achieved
• Individualize A1C target based on comorbidities
• Patient should monitor fasting and postprandial blood glucose levels
– Use agents with maximal efficacy, associated with lowest risk of hypoglycemia• Sulfonylureas are therefore much lower in algorithm
• Earlier use of incretin mimetics and DPP-4 inhibitors to stimulate insulin secretion without hypoglycemia
A1C = glycated hemoglobin; DPP-4 = dipeptidyl-peptidase 4
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS.
LoweringA1C
Preventing Hypoglycemia
Glycemic Management of Type 2 Diabetes: Treatment Goals
Individualized Algorithm
Risk of Hypoglycemia
• Plays a significant role in choice of agents in AACE algorithm
• For patients at highest risk of hypoglycemia, may consider close evaluation of agents chosen as well as therapeutic goal
• Patients with type 2 diabetes at highest risk of low blood glucose include those with:– Diabetes duration >15 years
– Advanced macrovascular disease
– Hypoglycemia unawareness
– Limited life expectancy
– Severe comorbidities
Garvey et al. Endocr. Pract. 2016;22 (Suppl 3); AACE/ACE Diabetes Algorithm Endocr. Pract. 2015;21 (Suppl1); AACE/ACE Obesity Algorithm Part 2
Current Antihyperglycemic Medications
Sulfonylureas
Generalized
insulin
secretagogue
12 Groups with Different Mechanisms of Action
-Glucosidase
Inhibitors
Delay CHO
absorption
Biguanide
Reduce hepatic
insulin
resistance
TZDs
Reduce
peripheral insulin
resistance
Amylin Analog
Suppress
glucagon
GLP-1 Analogs
Stimulate cells,
suppress
glucagon
Colesevelam
Bile acid
sequestrant
Bromocriptine
Hypothalamic
pituitary reset
Insulin
Replacement
Therapy
SGLT-2
Inhibitors
Block renal
glucose
reabsorption
Glinides
Restore
postprandial
insulin
patterns
DPP-4 Inhibitors
Restore
GLP-1 Level
Effect of Glucose-lowering Drugs on Patient Weight
1. Malone M. Ann Pharmacother. 2005;39:2046-2055. 2. Glipizide [package insert]. New York, NY; Pfizer; 2006. 3. Pioglitazone [package insert]. Deerfield, IL: Takeda Pharmaceuticals America; 2007. 4. Rosiglitazone [package insert]. Research Triangle Park, NC; GlaxoSmithKline; 2007. 5. Nathan DM, et al. Diabetes Care. 2008;31(1):173-175. 6. Holman RR. NEJM. 2007;357(17):1716-1730. 7. Metformin[package insert]. Princeton NJ; Bristol Meyers Squibb; 2009. 8. Sitagliptin [package insert]. Whitehouse Station, NJ; Merck and Co.; 2009. 9. Drucker DJ, et al. J Clin Invest. 2007;117(1):24-32. 10. Invokana [Package Insert] Janssen Pharmaceuticals, Inc. Titusville, NJ
SGLT-2 Inhibitors10
Therapeutic Options
GLP-1 receptor agonist9
Insulin5,6
DPP-4 inhibitor8
TZD3,4
Sulfonylurea1,2
Weight
Metformin7
A1C = glycated hemoglobin; DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; SGLT-2 = sodium glucose co-transporter-2; TZD = thiazolidinedione
Algorithm To Achieve Glycemic GoalsBaseline A1C 6.5% - 7.5%
• Monotherapy may be effective in this range
– Metformin first choice for monotherapy if no contraindications
– Consider DPP-4 if PP and FPG, GLP-1 if PP, TZD if metabolic syndrome or NAFLD, AGI if PP
– Do not recommend secretagogue (SU or glinide) in this range due to risk of hypoglycemia; short-lived effect
• If monotherapy is unsuccessful, move on to dual oral rx; often need to augment reduction in PP BG to get to goal in this A1C range
DPP-4=dipeptidyl peptidase-4; PP=post-prandial; FPG=fasting plasma glucose; GLP-1 = glucagon-like peptide-1; TZD=thiazolidinedione; NAFLD=non-alcoholic fatty liver disease; AGI=alpha-glucosidase inhibitor; SU=sulfonylurea; A1C=glycated hemoglobin; SGLT-2=sodium glucose transport-2
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS. Inzucchi S et al. Diabetes Care 2015;38:140-149.
Algorithm To Achieve Glycemic Goals Baseline A1C 7.6% - 9.0%
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS. Inzucchi S et al. Diabetes Care 2015;38:140-149.
• Dual therapy with metformin provides superior glycemic control over metformin alone.
• If dual oral rx is unsuccessful, consider triple therapy
• If triple oral rx fails to achieve A1C goal, initiate insulin
GLP-1 RA = glucagon-like peptide-1 receptor agonistDPP4-i=dipeptidyl peptidase 4 inhibitorTZD=thiazolidinedioneSGLT-2=sodium glucose cotransporter 2 inhibitorQR=quick-releaseAG-i=alpha-glucosidase inhibitorSU=sulfonylureaGLN=glinide
If patient is asymptomatic with
recent onset of disease and drug naïve, may
consider starting with dual or triple oral
regimens
Once A1C has improved to <7.5%, consider initiation of dual oral therapy with tapering and possible discontinuation of insulin rx
If symptomatic, start insulin
Algorithm to Achieve Glycemic Goals Baseline A1C > 9.0%
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS.
Add/Intensify Insulin
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS.
Intensify Prandial Control
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2017. Endocr Pract. 2017,doi:10.4158/EP161682.CS.
Prediabetes
Impaired Fasting Glucose (IFG):
FPG 100-125 mg/dL (5.6-6.9 mmol/l)
or
Impaired Glucose Tolerance (IGT):
2-h plasma glucose in the 75-g OGTT140-199 mg/dL (7.8-11.0 mmol/l)
or
A1C 5.7% to 6.4%
Handelsman Y et al. Endocrine Practice 2015;21 (Suppl 1)
A1C = glycated hemoglobin; FPG = fasting plasma glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OGTT = oral glucose tolerance test.
The Ticking Clock
Increased risk for both microvascular and macrovasculardisease begins early in the prediabetic state
– Insulin resistance is already present in patients with NGT who later develop T2DM
– Patients with prediabetes already have insulin resistance and significantly decreased beta-cell function
– Diabetic retinopathy, peripheral neuropathy, and nephropathy occur in patients with prediabetes
– Patients with prediabetes have a 2- to 3-fold increase in CHD risk, similar to patients with diabetes
CHD = coronary heart disease; NGT = normal glucose tolerance; T2DM = type 2 diabetes mellitus
AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm 2016. Endocr Pract. 2016;22(1):84-113;DeFronzo RA et al. Am J Cardiol. 2011;108(3 Suppl):3B-24B
Prediabetes Treatment Algorithm
T2DM = type 2 diabetes mellitusBP = blood pressureCVD = cardiovascular diseaseTZD = thiazolidinedioneGLP-1 RA= glucagon-like peptide-1 receptor agonist
• Weight-loss agents orlistat, lorcaserin, phentermine/topiramate and liraglutide can prevent progression to T2DM– Improve BP, triglycerides, and insulin sensitivity
• Metformin and acarbose can reduce progression to T2DM by 25% - 30% – Use for prediabetes is off-label
– Both are safe, confer CVD risk benefit; metformin is well tolerated
• TZDs prevented progression to T2DM in 60% -75% of patients in clinical trials– Associated with adverse outcomes
• GLP-1 receptor agonists may be as effective as TZDs– Promote weight loss, but inadequate safety data
Garber A et al. Endocr Pract. 2008;14 (7)933-946AACE/ACE Diabetes Algorithm Endocr Pract. 2017,doi:10.4158/EP161682.CS; AACE/ACE Obesity Algorithm Part 2