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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Medications to Treat Type 2 Diabetes:
Matching the Options to Needs
22.3 million people ( ̴ 7% of the population) have diagnosed DM• Additional 6.3 million undiagnosed
The number is growing by > 1 million per year
A major cause of mortality and morbidity
Cost (direct and indirect) $245 billion per year• 1 in 5 U.S. healthcare dollars spent
on diabetes
Diabetes in the U.S. Today: An Epidemic
Diabetes Care. 2013; 36(4):1033-1041
45% of Patients With Diabetes Are Still Not at ADA A1C Goal <7%*
49
50
51
52
53
54
55
56
A1c < 7% BP < 130/80 LDL < 100
*Ford ES. J Diabetes. 2011;3:337-347.
19% metall 3 goals
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Natural History of Type 2 Diabetes
Kendall DM, Bergenstal RM ©2003 International Diabetes Center, Minneapolis, MN. All rights reserved.
Prediabetes (IFG, IGT)Metabolic syndrome
Years
Glucose(mg/dL)
Relative Function
Clinical diagnosis
-10 -5 0 5 10 15 20 25 30
50
100
150
200
250
300
350
Insulin resistance
-cell function
Fasting glucose
Postmeal glucose
Onset ofDiabetesOnset ofDiabetes
0
50
100
150
200
250
126 mg/dL
7.0 mM
Adapted from Holman RR. Diab Res Clin Pract. 1998;40(suppl):S21-S25.
Years
-cell function(% of normal by HOMA)
0
20
40
60
80
100
-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6
Time of diagnosis
HOMA=homeostasis model assessment
Decline of -Cell Function in the UKPDS Illustrates Progressive Nature of Diabetes
1Chan JM et al. Diabetes Care. 1994;17:961-969.2Colditz G et al. Ann Intern Med. 1995;122:481-486.
Age-adjusted relative risk of type 2 diabetes
Obesity Is the Primary Risk Factorfor Type 2 Diabetes
0
10
20
30
40
50
1.02.2
12
42
0
25
50
75
100
1.08.1
40
93
<23 25 31 35 <22 25 31 35
Men1 Women2
BMI
2
Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
DPPOS Incidence of Diabetes
Risk Reduction18% with metformin34% with lifestyle
DPP: Diabetes Prevention Program; DPPOS: Diabetes Prevention Program Outcomes Study
DPPRG. Lancet. 2009 Nov 14;374(9702):1677-1686.
American Diabetes Association. Diabetes Care. 2013;36(suppl 1):S11-S66. American College of Endocrinology, Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocrine Practice. 2011;17(suppl 2):1-52.
A1C is “gold standard” measure of diabetes control over the previous 2–3 months
AMERICAN DIABETES ASSOCIATION (ADA) GOAL
A1C (%) < 7 Preprandial plasma glucose (mg/dL) 70–130
Peak postprandial plasma glucose (mg/dL) < 180
Aggressive Control of Diabetes: Glycemic Goals of Treatment
AMERICAN ASSOCIATION OF CLINICALENDOCRINOLOGISTS (AACE)
A1C (%) ≤ 6.5Preprandial plasma glucose (mg/dL) < 110 2-hour postprandial glucose < 140
ADA: Individualizing Therapeutic Goals
A1C ≤ 7% for most
A1C < 6.5% for selected patients, if safe
A1C < 8% for high-risk patients:
• History of severe hypoglycemia
• Short life expectancy / advanced age
• Advanced micro-/macrovascular complications and comorbidities such as:
– Heart disease
– Renal dysfunction
– Liver disease
• Longstanding diabetes
Consider weight management needs and goals in medication selection
ADA/EASD, Management of Hyperglycemia in Type 2 Diabetes: A patient-Centered Approach Diabetes Care 2012; 35:1364-1379. ADA, Diab Care 2013, 36(Suppl 1):S11.
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Sulfonylureas__________
Generalized insulin
secretagogues
Type 2 Diabetes
-Glucosidase
Inhibitors________
Delay carbohydrate absorption
Biguanide________
Reduces hepatic insulin
resistance
TZDs________
Reduce peripheral
insulin resistance
InsulinReplacement
Therapy
DPP-4 Inhibitors
Restore GLP-1 levels
Meglitinides __________
Restore postprandial
insulin patterns
ColesevelamMechanism unknown
SGLT2 Inhibitors Renal glucose
excretion
Quick-releaseBromocriptine
Central mechanismGLP-1
AnalogsStimulate cells
Glucagon
Pharmacotherapy Tailored for the Multiple Defects of Type 2 Diabetes
Classification Based on Target Pathology
Insulin Resistance• Biguanides (metformin)• Thiazolidinediones (pioglitazone)
β-Cell Dysfunction/Failure• Sulfonylureas (SU) • DPP-4 inhibitors (DPP-4-i)• Short-acting secretagogues (meglitinides/“glinides”)• GLP-1 receptor agonists (GLP-1-RA)• Insulin
Other Mechanisms• α-Glucosidase inhibitors (GI glucose absorption)• Colesevelam (hepatic, but exact mechanism not clear)• Bromocriptine (rapid-acting; dopaminergic mechanisms)• SGLT-2 inhibitors (renal glucose excretion)
Classification Based on Predominant Blood Glucose Effects Postprandial Glucose
• DPP-4 inhibitors
• α-Glucosidase inhibitors (AGI)
• Short-acting secretagogues (“glinides”)
• Short-acting insulin
Fasting Glucose• Biguanides (metformin)
General Glucose Reductions• Sulfonylureas
• Thiazolidinediones (pioglitazone)
• Bromocriptine (rapid-acting)
• Colesevelam
• SGLT-2 inhibitors
• Intermediate and long-acting Insulin
• GLP-1-RA
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Actions of Diabetes Medications
Drug Name Class How It WorksWhere It Works
Hypo-glycemia?
Metformin Biguanides Hepatic
glucose production
Liver Rare
SulfonylureasRepaglinideNateglinide
Secretagogues Insulin
secretionPancreas Yes
Pioglitazone Thiazolidinediones Insulin
sensitivityMuscle Rare
AcarboseMiglitol
α-GlucosidaseInhibitors
Slows CHOabsorption
Intestines Rare
Pramlintide Amylin analogs
Gastric emptying
Glucagon Satiety
Activates amylin receptor
With insulin
ADA/EASD. Management of Hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379. Data reported in package inserts.
Actions of Diabetes Medications (cont.)
Drug Name Class How It WorksWhere It Works
Hypo-glycemia?
ColesevelamBile Acid Sequestrants
Binds bile acids
Hepatic glucose production
Intestines Rare
ExenatideLiraglutide
GLP-1 agonists
Activates GLP-1 R Insulin Glucagon Gastric emptying Satiety
Pancreas;Stomach
Rare
SaxagliptinSitagliptinLinagliptinAlogliptin
DPP-4 inhibitors
Inhibits DPP-4 GLP-1, GIP Insulin Glucagon
Pancreas Rare
CanagliflozinSGLT-2inhibitors
Increases renalglucose excretion
Kidneys Rare
ADA/EASD. Management of Hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379. Data reported in package inserts.
Medications and Pharmacology
Description Action Examples
Medicationsimproving insulin action
Decrease insulin resistance Increase insulin sensitivity
Biguanide (metformin)Thiazolidinediones
Medicationsaugmenting the Incretin effect
Increase prandial insulinGLP-1 agonistsDPP-4 inhibitors
Insulin secretagoguesIncrease basal and/orprandial insulin
SulfonylureasShort-acting secretagogues
Other mechanisms
Renal glucose reabsorptionGI glucose absorptionHepatic glucose metabolismDopaminergic mechanisms
SGLT-2 inhibitorsα-Glucosidase inhibitorsColesevelamQuick-release bromocriptine
ADA/EASD. Management of Hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379. Data reported in package inserts.
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Estimated Reduction of A1C in Response to Monotherapy of Available Diabetes Medications
Adapted from Nathan DM. N Engl J Med. 2007;365:437-440. Package Inserts for canagliflozin, bromocriptine, colesevelam.
Medication Reduction in A1C
Insulin Injection 2.5
Metformin 1–1.5
Sulfonylureas 1–1.5
Short-acting secretagogues 1–1.5
Thiazolidinediones 1–1.3
GLP-1 analog 0.6–1.0
Α-Glucosidase inhibitors 0.5–0.8
Amylin analog 0.6–0.8
SGLT-2 inhibitors 0.6–0.7
DPP-4 Inhibitors 0.5–0.7
Bromocriptine (short-acting) 0.4–0.6
Colesevelam 0.4–0.5
Combination Therapy: Improvements in Glycemic Control When Adding a 2nd Medication
Regimen A1C FBG
Metformin + glyburide ~1.3% ~63 mg/dL
Metformin + repaglinide ~1.1% ~35 mg/dL
Metformin + exenatide ~0.9% ~24 mg/dL
Metformin + canagliflozin ~0.8% ~40 mg/dL
Metformin + pioglitazone (30 mg) ~0.8% ~38 mg/dL
Metformin + acarbose ~0.7% ~40 mg/dL
Metformin + sitagliptin ~0.7% ~17 mg/dL
Sulfonylurea + bromocriptine ~0.5% ~18 mg/dL
Metformin + colesevelam ~0.5% ~14 mg/dL
Insulin + antihyperglycemic meds. Open to target Open to target
Pivotal trial data reported in package inserts.
Antidiabetes Medications: Key Considerations in Advancing Therapy Metformin
• Usually first-line therapy with effective A1C reduction of 1–1.5 points
• No hypoglycemia or weight gain• Reduction in CV risk & mortality• Fasting glucose
Secretagogues (sulfonylureas, short-acting)• Good A1C impact: 1–1.5 point reduction• Inexpensive• Insulin secretion not glucose-dependent: general glucose-
lowering, short-acting, target postprandial• Potential for weight gain and hypoglycemia
α-Glucosidase inhibitors• Lesser efficacy (A1C 0.5–0.8 point reduction) but target
postprandial glycemia• Neutral effect on weight, lipids, and BP, but GI side effects• May prevent DM & reduce CV events (Stop-NIDDM Study)
Beaser RS. Joslin’s Diabetes Deskbook , 2nd updated ed. Boston, MA: Joslin Diabetes Center; 2010.
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Antidiabetes Medications: Key Considerations in Advancing Therapy Thiazolidinediones
• A1C reduction 1–1.3 points• Reduced peripheral insulin resistance: targets rising glycemia
during the day• Reduction in visceral fat but potential for weight gain / fluid retention• No hypoglycemia, but concern about other adverse events
DPP-4 inhibitors• Modest impact on A1C: 0.5–0.7 point reduction• Glucose-dependent impact on postprandial glycemia• Neutral impact on weight, lipids
GLP-1 agonists• Glucose-dependent insulin secretion and suppression of glucagon
targets postprandial glycemia and general glycemic lowering• Slows gastric emptying, can have AE of nausea• Reduced food intake and weight loss• Injected
Beaser RS. Joslin’s Diabetes Deskbook , 2nd updated ed. Boston, MA: Joslin Diabetes Center; 2010.Package inserts.
Antidiabetes Medications: Key Considerations in Advancing Therapy Colesevelam
• Modest A1C reduction: 0.5 points• Dual effect on LDL-C and A1C• General glycemic-lowering• Neutral effect on weight• Large number of large pills or dissolved powder
Quick-release bromocriptine• Modest impact on A1C: 0.6 points• Generalized glycemic-lowering• Neutral impact on weight, lipids• Unclear mechanism of action, multiple tablets
• SGLT-2 inhibitors• Modest impact on A1C: 0.6 points• Generalized glycemic-lowering• Weight loss
Beaser RS. Joslin’s Diabetes Deskbook , 2nd updated ed. Boston, MA: Joslin Diabetes Center; 2010.Package inserts.
Treatment Considerations in Overweight People Issues:
• Majority of people with type 2 diabetes are overweight or obese
• Consider latent autoimmune diabetes in adults (LADA) in lean people
Clinical approaches:• Intensive lifestyle program• Metformin• GLP-1 receptor agonists• Consider bariatric surgery
ADA/EASD. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379.
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Modest
Weight Gain Weight Neutral Weight Loss
Significant
Pioglitazone
SUsGlyburideGlipizide
InsulinNPHGlargineRegularAspartLisproGlulisine
SUsGlimepirideGlipizide XL
GlinidesRepaglinideNateglinide
InsulinDetemirGlulisine (PP)
Metformin
DPP-4 InhibitorsSitagliptinSaxaglipitinLinagliptin
α-Glucosidase InhibitorsAcarboseMiglitol
Colesevelam
Bromocriptine
GLP-1 AnalogsExenatideExenatide ERLiraglutide
Pramlintide
Modest
Based on Mitri J, Hamdy O. Expert Opin Drug Saf. 2009;8(5):573-584.
Obesity
Treatment Considerations in People With Renal Disease
Issues:• Increased risk of hypoglycemia
• Metformin and lactic acidosis
Clinical approaches:• US: Stop metformin @ SCr > 1.5 (men),
1.4 (women)
• UK: dose @ GFR <45, stop @ GFR < 30
• Caution using sulfonylureas (esp. glyburide)
• DPP-4 inhibitors: adjust doses (except linagliptin)
• Avoid exenatide if GFR < 30
ADA/EASD. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379.
Renal Disease (Slide 1 of 2)
Sulfonylureas Meglitinides -Glucosidase Inhibitors(Acarbose, Miglitol)
TZDs (Pioglitazone)
Do not use if:
eGFR<60 (nateglinide)
Cr>2 (~eGFR<30)
Other notes
Glipizide: less hypoglycemia
Repaglinide: no dose adjustment
Concerns re: fluid retention, edema, bone disease, bladder Ca
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Renal Disease (Slide 2 of 2)
Biguanides (Metformin)
GLP-1 Agonists
DPP-4 Inhibitors
SGLT-2 Inhibitors
Use with caution if:
eGFR 45–60
Adjust dose if:
eGFR 30–45 (maximum 1000 mg/d)
eGFR ≤ 50 eGFR 45–60 (max 100 mg/d)
Do not use if:
eGFR <30 eGFR < 30 (exenatide)
eGFR < 45
Other notes
D/C for inpatients if lactic acidosis risk
Liraglutide: no dose adjustment
Treatment Considerations in People With Liver Dysfunction
Issues:• Most drugs not tested in advanced liver
disease
Clinical approaches:• Pioglitazone may help steatosis
• Insulin is the best option if disease is severe
ADA/EASD. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379.
Abnormal Liver Function
Ding X et al. Hepatology. 2006;43:173-181.Cusi K. Curr Opin Endocrinol Diabetes Obes. 2009;16:141-149.Williams KH et al. Endocr Rev. 2013;34(1):84-129.
Biguanides(metformin)
TZDs (pioglitazone) Incretins (exenatide,liraglutide)
Pros • Insulin sensitization
• Weight neutral• May improve
LFTs
• Insulin sensitization• May improve LFTs• May improve steatosis,
inflammation
• Weight loss• May improve
steatosis
Cons Potential for:• Weight gain• Edema• Heart failure
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Coronary Artery Disease and Glycemic ControlACCORD
• Intensive (A1C < 6%) vs standard (7–8%)• Increased mortality in intensive arm• ? role of hypoglycemia
ADVANCE • Intensive (A1C < 6.5%) vs standard• No change in mortality
VADT• Intensive (A1C < 6%) vs standard• Longer DM duration less CVD benefit
Summarized in ADA Clinical Practice Recommendations, 2013.
Treatment Considerations in People With Heart Disease Coronary artery disease:
• Metformin has CVD benefit (UKPDS)• Avoid hypoglycemia• Sulfonylureas and ischemic preconditioning• Possible CVD effects with pioglitazone, incretin-
based therapies, α-glucosidase inhibitors, bromocriptine
Heart failure:• Metformin OK unless unstable or severe• Avoid thiazolidinediones• Incretin-based therapies ? CV protection
ADA/EASD. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364-1379.
Preventing CVD Events
Measure Change in Measure CVD Risk Reduction
A1C 1% 14%
Systolic BP 10 mm Hg 11%
LDL-C 1 mmol/L (≈ 40 mg/dL) 25%
Stratton IM et al. Diabetologia. 2006 Aug;49(8):1761-1769. (based on UKPDS) Yusuf S. Lancet. 2002 Jul 6;360(9326):2-3. (based on MRC/BHF Heart Protection Study [HPS])
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Coronary Artery Disease –Effects of Specific Meds
Metformin SUs TZDs (pioglit-azone)
DPP-4i GLP-1a
Lipid effects
↓TG, ↑HDL, ↔ LDL-C
None ↓↓TG, ↑↑HDL, ↔ LDL-C
↓post-prandial lipids
↓↓non-HDL
BP effects
None None None None ↓
CVD event rates
↓* ↓* ↓*
Davidson MH. Am J Cardiol. 2012;110[suppl]:43B–49B.Canagliflozin package insert.
*nonrandomized trials
Coronary Artery Disease –Effects of Specific Meds
Bile acid sequestrants (colesevelam)
SGLT-2 inhibitors
Meglitinides
Lipid effects ↓↓non-HDL ↑LDL None
BP effects ↓ None
CVD event rates
Unknown Unknown
Davidson MH. Am J Cardiol. 2012;110[suppl]:43B-49B. | Derosa G. J Clin Pharm Ther.2009 Feb;34(1):13-23. | Derosa G. Curr Med Res Opin. 2009 Mar;25(3):607-615.Canagliflozin package insert.
*nonrandomized trials
Treatment Considerations in Older Adults Issues:
• Reduced life expectancy• Higher cardiovascular disease (CVD) burden• Reduced GFR• At risk for adverse events from polypharmacy• More likely to be compromised from hypoglycemia
Clinical approaches:• Less ambitious targets• A1C < 7.5–8.0% if tighter targets not easily
achieved• Focus on drug safety
ADA/EASD. Management of hyperglycemia in type 2 diabetes: a patient-centered approach Diabetes Care. 2012;35:1364-1379.
11
Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
Elderly (slide 1 of 2)
Medication Hypoglycemia Risk
Advantages Cautions
Metformin Low • Cardiovascular benefits• Reduced dose safe for
eGFR ≥ 45
• GI side effects• Unintended weight loss• Renal insufficiency
Sulfonylureas(glipizide)
Higher • Well tolerated • Inconsistent meals lead to hypoglycemia
Nonsulfonylurea secretagogues (glinides)
Lower than SUs • May skip dose if meal is skipped
• Multiple doses (error-prone)
• Expensive
glucosidase inhibitors
Low • GI side effects are common
Germino, FW. Clin Ther. 2011;33(12):1868-1882.
Elderly (slide 2 of 2)
Medication Hypoglycemia Risk
Advantages Cautions
DPP-4 inhibitors Low • Expensive
GLP-1 agonists Low • Unintended weight loss• Expensive• Needs injections
Thiazolidinediones(pioglitazone)
Low • Possible bladder cancer risk• Leg edema, CHF
SGLT-2 inhibitors Low • Limit to 100 mg/day if >75years
Insulin Higher • Well tolerated • Complex regimen can lead to errors
Germino, FW. Clin Ther. 2011;33(12):1868-1882.
Principles of Starting and Advancing Therapy
AACE and ADA Guidelines
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
ADA/EASD Position Statement
From Inzucchi S et al. ADA EASD position statement. Diabetes Care. 2012;35:1364-1379.]
Healthy eating, weight control, increased physical activity
Initial drug monotherapy
2-drug combinations
Metformin
Efficacy
Hypoglycemia
Weight
Cost
Side effects
Efficacy A1CHypoglycemiaWeight
CostSide effects
HighLow riskNeutral / lossGI / lactic acidosisLow
If A1C not at goal at 3 months, proceed to 2 drugs. (No specific order)
Met + Met + Met + Met + Met +SU TZD DPP-4i GLP-1-RA Insulin High High Intermediate High HighestModerate risk Low risk Low risk Low risk High risk
Gain Gain Neutral Loss GainHypo-glycemia
Edema, CHF, Fx Rare GI Hypo-
glycemiaLow High High High Variable
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Joslin Diabetes CenterJoslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose ControlMedications to Treat Type 2 Diabetes: Matching the Options to Needs
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express written permission of Joslin Diabetes Center is prohibited.
ADA/EASD Position StatementHealthy eating, weight control, increased physical activity
3-drug combin-ations
More complex insulin strategies
Met + Met + Met + Met + Met +
SU TZD DPP-4i GLP-1-RA Insulin
+ + + + +
TZD SU SU SU TZD
or DPP-4-I or DPP-4i or TZD or TZD or DPP-4i
or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA
or Insulin or Insulin
If A1C not at goal at 3–6 months, proceed to a more complex insulin strategy + 1–2 noninsulin agents
Insulin (multiple daily doses)
If A1C not at goal after 3 months, proceed to 3-drug combination (no specific order)
From Inzucchi S et al. ADA EASD position statement. Diabetes Care. 2012;35:1364-1379.]
Treatment of Type 2 Diabetes:Key Points Individualize treatment targets and methods,
consider comorbidities (esp. CVD, renal, liver) and age-related issues
Consider weight management needs and goals in designing treatments
Nutrition, exercise, education: foundation of any treatment program
Metformin is first-line pharmacotherapy—unless there is a contraindication
After metformin, advance to 1–2 medications that are most appropriate for the patient
Treatment of Type 2 DM:Key Points
Ultimately many patients will require insulin, alone or in combination with other medications
Make all treatment decisions with the patient, focusing on her or his preferences, needs, and values
Comprehensive CV risk reduction is vital!
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