© 2012 Virginia Mason Medical Center
Jonathan Stoehr, MD PhDEndocrinology, Diabetes, Metabolism and NutritionVirginia Mason Medical CenterSeattle, WA
© 2012 Virginia Mason Medical Center
There is no conflict of interest that could be perceived as prejudicing the impartiality of this review.
© 2012 Virginia Mason Medical Center
Review the tenets of the Shared Decision Making Model
Discuss the application of the Shared Decision Making model to diabetes care.
Review the important clinical properties of the available medications for type 2 diabetes.
© 2012 Virginia Mason Medical Center
Patient
Physician Provider Proposes Treatment
Patient expresses Resistance
Provider presents Evidence
Patient expresses Resistance
Both experience Frustration
© 2012 Virginia Mason Medical Center
Physician Patient
Support patient Self Determination
Develop relational autonomy.
Educate, Provide Options
Elicit preferences based on value judgements
© 2012 Virginia Mason Medical Center
Physician Patient
© 2012 Virginia Mason Medical Center
Insulin Biguanides (Metformin) Sulfonylureas (Glimepiride, Glipizide, Glyburide, etc.) Meglitinides (Repaglinide, etc.) IncretinAgonists (Exenatide, Liraglutide) Once‐Weekly (Exenatide, Dulaglutide, Albiglutide)
DPP‐4 Inhibitors (Sitagliptin, Saxagliptin, etc.) SGLT2 inhibitors (Canagliflozin, etc.) Thiazolidinediones (Pioglitazone) A‐Glucosidase Inhibitors (Acarbose, Miglitol) Bile Acid Sequestrant (Colesevalam) Amylin Mimetic (Pramlintide) Dopamine‐2r Agonist (Bromocriptine)
© 2012 Virginia Mason Medical Center
Recommended first-line therapy by all major clinical practice guidelines: ADA, ACP, AACE
Metformin offers multiple secondary benefits: Stabilization in body weight, or modest weight loss. Improvement in serum lipid profile (LDLc, TG) Likely reduction in cardiovascular events
(UKPDS 10-year extension) Mortality / Survival benefit in certain populations Lower Cancer Incidence, fewer cancer deaths
ADA Standards of Medical Care in Diabetes, 2014
© 2012 Virginia Mason Medical Center
Treatment is Individualized Cost? Efficacy? Side Effects? Effect on Weight? Hypoglycemia Risk? Secondary Benefits?
© 2012 Virginia Mason Medical Center
Efficacy: High. Can be titrated accurately. Hypoglycemia risk: Very high Weight: Typical gain 2‐4 kg/year
© 2012 Virginia Mason Medical Center
• Induces differentiation of new adipocytes from precursors.• Cross‐agonist of IGF‐1 receptor leading to somatotropicchanges, pseudo‐acromegaloid features.
High Doses
•Hypoglycemia increased intake of rescue carbohydrates.•Hypoglycemia induces surge in cortisol, HGH, ghrelin.•Often, high CHO intake to prevent hypoglycemia.
High Doses
• Induces Lipoprotein Lipase expression and glucose uptake.• Stimulates de novo biosynthesis of fatty acids and TG.• Increased uptake of carbs and fats into tissues.
Physiologic Doses
•Suppresses glycosuria / polyuria.Low Doses
•Suppresses ketoacidosis. Blocks muscle catabolism.•Allows anabolic effects of resistance training / exercise.Low Doses
© 2012 Virginia Mason Medical Center
Insulin Therapy
Weight Gain
Worsening Insulin Resistance
Worsening Glycemic Control Requiring
more Insulin
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: High Hemoglobin A1c (>10%). Longstanding “burned out” diabetes,
or no response to sulfonylureas. Can tolerate weight gain. Regular / predictable diet and exercise regimen in order to minimize
hypoglycemia risk.
Drug Name Avg Retail Cost* per month “Metformin Index”
Insulin Glargine (Lantus®) $397.36 / vial (33 units / d) 99 patients
Insulin Detemir (Levemir®) $347.14 / vial (33 units / d) 87 patients
Insulin NPH (Humulin® N) $66.88 / vial (33 units / d) 17 patients
© 2012 Virginia Mason Medical Center
Efficacy: Very good. 1.0‐1.5% A1c lowering Hypoglycemia risk: High Weight: Weight gain common Side Effects: Higher risk of progression to insulin requirement
Secondary Benefits: convenient dosing
Glimepiride (Amaryl®), Glipizide (Glucotrol®), Glyburide (Micronase®)
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: Desire to minimize cost of medications. Desire to avoid “injectables.” Lean. Can tolerate some weight gain. Regular / predictable diet and exercise regimen in order to minimize hypoglycemia risk.
Drug Name Avg Retail Cost* per month “Metformin Index”
Glipizide (Glucotrol®) $7.83 2 patients
Glyburide (Micronase®) $6.00 1.5 patients
Glimepiride (Amaryl®) $8.00 2 patients
© 2012 Virginia Mason Medical Center
Mechanism: Mimics the effects of anti‐diabetic hormone GLP‐1 Blocks release of hormone glucagon Stimulates growth and secretory activity of pancreatic beta cells. Slows emptying of stomach reduced portion sizes. Stimulates NTS in brainstem weight loss.
Exenatide (Byetta®, Bydureon®), Liraglutide (Victoza®),Dulaglutide (Trulicity®), Albiglutide (Tanzeum®)
© 2012 Virginia Mason Medical Center
Efficacy: Intermediate. 0.8‐1.2% A1c lowering Side Effects: Nausea, vomiting (particularly after large meal) Diarrhea, headache Rare: hemorrhagic pancreatitis Potential: c‐cell hyperplasia (rodent model)
Hypoglycemia risk: Minimal. Weight: Sustained modest weight loss.
Exenatide (Byetta®, Bydureon®), Liraglutide (Victoza®),Dulaglutide (Trulicity®), Albiglutide (Tanzeum®)
© 2012 Virginia Mason Medical Center
Exenatide in lipid microsphere emulsion. Rapid release of surface‐bound exenatide.
Slow release of embedded exenatide over 10 weeks (peaks at week 2 and weeks 6‐7).
Standard dosing: 2mg SQ, weekly. Supplied as single dose pens. Protocol for administration is complex, requires multiple steps.
Bydureon® prescribing information, Amylin Pharmaceuticals, 2012
© 2012 Virginia Mason Medical Center
Modified Human GLP‐1 hormone, linked to albumin.
Serum T1/2= 4‐7 days.
Supplied as single dose pens. Protocol for administration is complex, multiple steps, taking at least 15 minutes.
Pancreatitis was observed in RCTs.Tanzeum® prescribing information, 2014
© 2012 Virginia Mason Medical Center
Modified Human GLP‐1 hormone, linked to Fc fragment of immunoglobulin.
Serum T1/2= 5 days.
Efficacy is inferior to liraglutide
Supplied as single dose pens.Administration protocol is simpler.
Significantly more expensive. Pancreatitis was observed in RCTs.
Trulicity® prescribing information, 2014
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: Obese. Desire for modest weight loss. Desire to avoid hypoglycemia Suitable insurance. Willing to pay more for medications.
Drug Name Avg Retail Cost* per month “Metformin Index”
Exenatide (Byetta®) $442.74 110 patients
Exenatide (Bydureon®) $455.92 114 patients
Liraglutide (Victoza®) $607.02 152 patients
Albiglutide (Tanzeum®) $339.86 85 patients
Dulaglutide (Trulicity®) $1001.74 250 patients
© 2012 Virginia Mason Medical Center
Mechanism: Blocks the degradation of theanti‐diabetic hormone GLP‐1 Blocks release of hormone glucagon Stimulates growth and secretory activity of pancreatic beta cells.
Sitagliptin (Januvia®), Saxagliptin (Onglyza®), Linagliptin (Tradjenta®), Alogliptin (Nesina®)
© 2012 Virginia Mason Medical Center
Efficacy: 0.8‐1.1% lowering of HgbA1c Side Effects: generally well tolerated. Nausea is generally mild
Hypoglycemia risk: minimal. Weight: Neutral. No significant gain or loss. Secondary Benefits: Once Daily Dosing
Sitagliptin (Januvia®), Saxagliptin (Onglyza®), Linagliptin (Tradjenta®), Alogliptin (Nesina®)
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: Desires convenience of once‐daily pill dosing. Desires a very mild side‐effect profile. Desires to avoid weight gain. Desires oral medications over “injectables.” Willing to pay more for medications.
Drug Name Avg Retail Cost* per month “Metformin Index”
Sitagliptin (Januvia®) $161.32 40 patients
Linagliptin (Tradjenta®) $314.36 79 patients
Alogliptin (Nesina®) $297.06 74 patients
Saxagliptin (Onglyza®) $309.01 77 patients
© 2012 Virginia Mason Medical Center
Efficacy: Modest. 0.5‐0.8% lowering of HgbA1c
Side Effects: Fluid Retention Contraindicated in heart failure. Avoid in heart disease
Weight: Typical gain 2‐4 kg/year. Hypoglycemia risk: minimal. Secondary Benefit: Once Daily Dosing,treats Non‐Alcoholic Fatty Liver Disease
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: No heart disease. Desire to minimize cost of medications. Desire convenience of once‐daily pill dosing. Desire oral medications over “injectables.” Willing to tolerate weight gain.
Drug Name Avg Retail Cost* per month “Metformin Index”
Pioglitazone (Actos®) $15.87 4 patients
© 2012 Virginia Mason Medical Center
Mechanism: Blocks intestinal alpha‐glucosidase impairs digestion of disaccharides / polysaccharides Reduces postprandial glucose. Unabsorbed carbohydrates are fermented into gas by intestinal flora.
Acarbose (Precose®), Miglitol (Glycet®)
© 2012 Virginia Mason Medical Center
Efficacy: Decent. 0.8‐1% lowering of HgbA1c Side Effects: Flatulence (esp after high‐carbmeal), can cause uncomfortable abdominal cramps / colicky pain.
Weight: Neutral. Hypoglycemia risk: Minimal. Secondary Benefits: Fewer Heart attacks observed in clinical trials. Also indicated for prevention of diabetes.
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: Desire oral medications over “injectables.” Desire modest weight loss. Desire to reduce medication costs. Willing / able to significantly reduce carb intake, or tolerate significant gas & flatulence.
Drug Name Avg Retail Cost* per month “Metformin Index”
Acarbose (Precose®) $37.24 9 patients
© 2012 Virginia Mason Medical Center
Canagliflozin (Invokana®): approved by FDA in 2013 Dapagliflozin (Farxiga®): approved by FDA in 2014 Empagliflozin (Jardiance®): approved by FDA in 2014
Works by blocking the SGLT2 glucose symporterin the proximal tubuleof the nephron. Effect: far greater excretion of glucose in urine.
Glucose pulls salt/water into urine by osmosis osmotic diuresis dehydration / thirst.
© 2012 Virginia Mason Medical Center
Adverse effects: Dehydration can potentially injure kidneys Risk of UTIs & genitourinary infections ▪ Especially, Females
Dapagliflozin: Increased Bladder Cancer in RCTs New Medication class: unknown potential risks.
© 2012 Virginia Mason Medical Center
Efficacy: Decent. A1c reduction 0.7‐1.0% Side Effects: Polyuria, hypovolemia (even kidney Injury). Glycosuria UTIs & genitourinary infections. Dapagliflozin: increased bladder Ca in RCTs.
Hypoglycemia risk: Intermediate. Slightly higher risk vs. placebo.
Weight: Modest weight reduction 2‐4%
Canagliflozin (Invokana) Prescribing Information
© 2012 Virginia Mason Medical Center* Data are average of 1-month retail price from Walmart and Costco pharmacies.
Generics used when possible. Source: www.goodrx.com, accessed on 12/3/2014.
Ideal Patient: Desires convenience of once‐daily pill dosing. Desires modest weight loss. Desires oral medications over “injectables.” Willing to pay more for medications.
Drug Name Avg Retail Cost* per month “Metformin Index”
Canagliflozin (Invokana®) $325.64 81 patients
Dapagliflozin (Farxiga®) $325.64 81 patients
Empagliflozin (Jardiance®) $314.36 78 patients
© 2012 Virginia Mason Medical Center
Support patient Self Determination
Develop relational autonomy.
Educate, Provide Options
Elicit preferences based on value judgements
© 2012 Virginia Mason Medical Center
© 2012 Virginia Mason Medical Center
© 2012 Virginia Mason Medical Center
© 2012 Virginia Mason Medical Center
FDA approved in 2009 Treatment of Type 2 DM In addition to Metformin, Sulfonylurea, or Insulin
Unknown Mechanism of Action Efficacy: Modest
Hgb A1c benefit: 0.5% Adverse Effects:
Nausea, dizziness, rhinitis common.
Pijl H, et al. Diabetes Care 23:1154–1161
© 2012 Virginia Mason Medical Center
FDA approved in 2008 for Treatment of Diabetes: In addition to Metformin, SU,
or Insulin Unknown Mechanism of
Action GLOWS Trial Improved LDLc Modest Hgb A1c reduction
(0.5%, greater in patients with higher starting A1c).
Zieve FJ, et al. Clinical Therapeutics: 29(1): 74-83
ADVERSE EFFECTS:9/29 (29.0%) subjects in colesevelam arm3/34 (8.8%) subjects in placebo armGastrointestinal disorders 22.6%Constipation 19.4%
Top Related