jonathan stoehr, md phd endocrinology, diabetes ...€¦ · drug name avgretailcost* per month...

© 2012 Virginia Mason Medical Center

Jonathan Stoehr, MD PhDEndocrinology, Diabetes, Metabolism and NutritionVirginia Mason Medical CenterSeattle, WA


There is no conflict of interest that could be perceived as prejudicing the impartiality of this review.


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.


Patient

Physician Provider Proposes Treatment

Patient expresses Resistance

Provider presents Evidence

Patient expresses Resistance

Both experience Frustration


Physician Patient

Support patient Self Determination

Develop relational autonomy.

Educate, Provide Options

Elicit preferences based on value judgements


Physician Patient


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)


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


Treatment is Individualized Cost? Efficacy? Side Effects? Effect on Weight? Hypoglycemia Risk? Secondary Benefits?


Efficacy: High. Can be titrated accurately. Hypoglycemia risk: Very high Weight: Typical gain 2‐4 kg/year


• 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


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


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®)



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.


Glipizide (Glucotrol®) $7.83 2 patients

Glyburide (Micronase®) $6.00 1.5 patients

Glimepiride (Amaryl®) $8.00 2 patients


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®)


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®)


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


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


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



Ideal Patient: Obese. Desire for modest weight loss. Desire to avoid hypoglycemia Suitable insurance. Willing to pay more for medications.


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


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®)


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®)



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.


Sitagliptin (Januvia®) $161.32 40 patients

Linagliptin (Tradjenta®) $314.36 79 patients

Alogliptin (Nesina®) $297.06 74 patients

Saxagliptin (Onglyza®) $309.01 77 patients


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



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.


Pioglitazone (Actos®) $15.87 4 patients


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®)


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.



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.


Acarbose (Precose®) $37.24 9 patients


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.


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.


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



Ideal Patient: Desires convenience of once‐daily pill dosing. Desires modest weight loss. Desires oral medications over “injectables.” Willing to pay more for medications.


Canagliflozin (Invokana®) $325.64 81 patients

Dapagliflozin (Farxiga®) $325.64 81 patients

Empagliflozin (Jardiance®) $314.36 78 patients


Support patient Self Determination

Develop relational autonomy.

Educate, Provide Options

Elicit preferences based on value judgements


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


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%

jonathan stoehr, md phd endocrinology, diabetes ...€¦ · drug name avgretailcost* per month...

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