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Management of Adult Diabetes Mellitus
Clinical Practice Guideline July 2013
This clinical practice guideline is based on: Standards of Medical Care for Diabetes-2013 found in Diabetes
Care Volume 36, Supplement 1, January 2013. MSH Ambulatory Best Practices Committee endorses this
guideline.
General Principles
Hyperglycemia is the pathognemonic feature of all forms of diabetes. Treatment aimed at lowering blood
glucose levels to or near normal in all patients is mandated by the following proven benefits:
The danger of acute decompensation due to diabetic ketoacidosis or hyperosmolar hyperglycemic non-ketotic syndrome, with their accompanying morbidity and mortality, is markedly reduced. The risk of blurred vision, polyuria, polydipsia, fatigue, and weight loss with polyphagia, vaginitis, or balanitis, days missed from work, emergency room visits and hospital admissions may be reduced. The risks of development or progression of diabetic retinopathy, nephropathy, and neuropathy are all greatly decreased. These complications may even be prevented by early normalization of metabolic status. Targeted blood glucose control has been demonstrated to be associated with a less atherogenic lipid profile, and fewer macrovascular events.
Achieving near normal or normal blood glucose levels in patients with any type of diabetes requires
comprehensive training in self-management and, for most individuals, intensive treatment programs. Such
programs include the following components according to individual patient need: frequent self monitoring of
blood glucose (SMBG), meticulous attention to meal planning, regular exercise, physiologically based insulin
regimens, instruction in the prevention and treatment of hypoglycemia and other acute and chronic
complications, sick day guidelines, when to call the doctor or go to the Emergency Room, continuing education
and reinforcement, and periodic assessment of treatment goals.

PRE-DIABETES- Patients with a predisposition to diabetes (prediabetes) are individuals with impaired fasting
glucose (IFG), impaired glucose tolerance (IGT), or an A1C of 5.7-6.4% some of whom in fact already have the
characteristic microvascular changes associated with diabetes. Early identification of individuals with pre-
diabetes will provide opportunities for lifestyle management and potentially prevention of complications related
to diabetes.
I. Screening: Targeted screening for pre-diabetes is recommended for the populations at high risk for
development of diabetes. II. Treatment:
Lifestyle modification is the fundamental treatment and should be reinforced at every visit Exercise moderate intensity for 30-60 minutes 5 days a week to achieve weight loss of 5-10% of Diet includes calorie restriction/portion control, increased fiber intake and possible limitation in carbohydrate intake, lower sodium and avoidance of excess alcohol Weight loss maintenance as long term goal Pharmacotherapy: Metformin may be considered in those who are at very high risk for developing diabetes (combined IFG and IGT plus other risk factors) Monitoring for the development of diabetes in those with pre-diabetes should be performed Screening for and treatment of modifiable risk factors for CVD is suggested III. Goals of Management- individuals with prediabetes should have the same lipid and BP goals as those
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Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 with Diabetes (page 3).
DIABETES
I. Screening for Diabetes
The primary purpose of a screening program is to identify individuals without symptoms who are likely to meet the diagnostic criteria for diabetes or pre-diabetes. Testing should be considered for all adults who are overweight (BMI >25 kg/m2) and have additional risk factors below. Otherwise screening should begin at age 45 and then every 3 years if normal.  First degree relative w/Diabetes Mellitus  Polycystic Ovarian Disease  Women diagnosed with gestational  Thyroid disease diabetes (or delivered a baby weighing >  HDL level < 35 mg/dl and/or Triglyceride 9lbs ie, macrosomia  African-American, Native American,  Hypertension > 140/90 mmHg or on therapy Latino, Asian American, Pacific Islander  Are habitually physically inactive  Other clinical conditions associated with  A1C > 5.7%, Impaired Glucose Tolerance insulin resistance: severe obesity, (IGT) or Impaired Fasting Glucose (IFG) on acanthosis nigricans previous testing  History of vascular disease II. Classification (4 clinical classes classification criteria, 1997 American Diabetes Association)
 Type 1 diabetes (B-cell destruction, usually leading to absolute insulin deficiency)
 Type 2 diabetes (results from a progressive insulin secretory defect on a background of insulin
 Other specific types of diabetes (due to other causes, e.g. genetic defects in B-cell function, genetic
defects in insulin action, disease of the exocrine pancreas (pancreatitis, pancreatectomy), drug –e.g. glucocorticoid- or chemical induced).  Gestational Diabetes Mellitus (diagnosed during second or third trimester of pregnancy)
III. Criteria for the Diagnosis of Diabetes Mellitus
Three ways to diagnose diabetes are possible. If diagnosis made based on A1C or FPG should be confirmed on a subsequent day. FPG 126 mg/dl Two-hour 75gm (7.0 mmol/l)*
OGTT: plasma glucose glucose 200 Fasting is (2hPG) 200 mg/dl* certified lab defined as no (glucose load caloric intake containing the plus symptoms of for at least 8 hrs. equivalent of 75g anhydrous glucose dissolved in water) 75-g OGTT:140 -199 FPG <100 mg/dl 2hPG <140 mg/dl * In the absence of unequivocal hyperglycemia with acute metabolic decompensation, one of these three
tests should be confirmed by repeat testing ** Increased risk for diabetes- risk is continuous, extending below the lower limit of the tests range and
Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 becoming disproportionately greater at the higher ends of the range. If both an A1C and fasting PG obtained and only one test result Meets diagnostic cut-point for pre-diabetes, repeat just the test that was abnormal for confirmation of
IV. Initial Evaluation
A. Complete medical history and physical, including assessment of fundi (dilated eye exam), teeth and gums, thyroid, carotids, reflexes, monofilament exam, (vibratory sensation acceptable), evaluation of pedal pulses by palpation and with carotid & femoral auscultation. B. Obtain baseline laboratory studies:  Hemoglobin A1C  Fasting Lipid Profile  Urinalysis for ketones, proteins  Serum Creatinine and eGFR calculation  Spot Urine Microalbumin/creatinine (all Type 2, for Type 1 diabetics, if diagnosed >5 yrs) C. Discuss and document a management plan which includes:  Weight goals  Education  Smoking Cessation  Glucose monitoring  Activity  Healthy Coping D. Referrals if indicated: Medical Nutrition Therapy (MNT)*  Ophthalmologist- dilated eye exam (initial Diabetes Self Management* Education diagnosis and then annually) Family planning for women of  Behavioral specialist reproductive age * Most payors provide coverage for MNT and/or DSME for diabetes patients with a provider referral/ prescription to a certified diabetes educator. Specify: type of diabetes; MNT for nutrition/meal planning; DSME for other services. V. Goals of Treatment for Diabetes
A. Achieve near normalization of blood glucose, as evidenced by A1C as close to 7% as possible which may decrease the risk of development and/or progression of retinopathy, nephropathy, neuropathy or cardiovascular disease. B. Key concepts in setting & attaining glycemic goals: A1C is the primary target for glycemic control Goals should be individualized based on; duration of diabetes, age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemic unawareness, individual patient considerations. More or less stringent glycemic goals may be appropriate for individual patients. Postprandial glucose should be targeted if AIC goals are not met despite reaching preprandial glucose goals. Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Glycemic control
The A1C goal for patients in general is <7%. The A1C goal for the individual patient is an A1C as close to normal as possible without significant hypoglycemia Preprandial plasma 70–130 mg/dl (3.9–7.2 mmol/l) glucose Postprandial plasma <180 mg/dl (<10.0 mmol/l) glucose**
Blood pressure
< 140/80 mmHg but <130/80 mmHg maybe be appropriate for certain patients if it can be achieved without undue treatment burden Lipids***
Target Goal < 100 mg/dl, Optional<70 mg/dl (<2.6 mmol/l) Statin therapy should be initiated for all patients with diabetes regardless of LDL level who have h/o cardiovascular disease or who are >40 old with one or more CV risk factor(s) <150 mg/dl (<1.7 mmol/l) >40 mg/dl (1.1 mmol/l) for males, and HDL goal > 50mg/dl (1.3mmol/l) in women
*Referenced to a nondiabetic range of 4.0–6.0% using a DCCT-based assay; ADA Standards of care for
Medical management of diabetes mellitus. 2007
**Postprandial glucose measurements should be made 1 ½ to -2 h after the beginning of the meal, generally
peak levels in patients with diabetes. ***Current NCEP/ATP III guidelines suggest that in patients with triglycerides >/= 200 mg/dl, the "non-
HDL cholesterol" (total cholesterol minus HDL) be utilized. The goal is 130 mg/dL. VI. Referrals
A. Provide and document Medical Nutrition Therapy B. Provide and document diabetes education in the areas of:  Administration of medication  Pregnancy Counseling  Glucose Monitoring (SMBG)  Coping with disease  Symptoms of hyper/hypoglycemia  Smoking Cessation  Diet/Nutrition C. Referral to Podiatry is recommended when: High risk patient (neuropathy, vascular Sensorimotor deficiencies for foot wear disease, structural deformities, abnormal gait) Hx. of previous ulcers or infections Skin/nail deformities D. Yearly referral to ophthalmology for dilated exam E. Referral to Endocrinology is recommended when: The initial clinical and/or biochemical state is markedly abnormal The response to standard therapy is unsatisfactory,(i.e. A1C goal not attained in 6-12 months) Metabolic complications. F. Consider a referral to Cardiac or Vascular Specialist when: Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 EKG, with left bundle branch block, myocardial infarction, or change from baseline at any time. Decline in exercise capacity Angina, atypical chest pain or claudication Absent or diminished pedal pulses Abdominal aortic aneurysm Embarking on new exercise program if previously sedentary and/or over 40 years old, or VII. Continuing Care
Recommended intervals for continuing care: Recommended Interval
Frequency of return visits At least quarterly * for Type 1 patients. At least semi-annually * for Type 2 patients if A1C at goal; quarterly if not at goal. *More frequently when indicated for follow up of DKA, hyperglycemia, hypoglycemia, hypertension, retinopathy, nephropathy, cardiovascular disease, neuropathy, or foot conditions. Review of Management Plan During every regular follow up visit Focused physical, including reflexes and monofilament exam Quarterly for Type 1 diabetes or Insulin any using patients and poorly controlled patients; Every 6 months for Type 2 diabetes with A1C< 7.0%. Fasting lipid profile Annually, Target Goal < 100 mg/dl, Optional<70 mg/dl (<2.6 mmol/l) Hepatitis B vaccine All adult 19 to 59 yo and consider vaccination in adults 60 yo and older Pnuemococcal vaccine At time of diagnosis, repeat vaccination is recommended for individuals 64 years of age previously immunized when they were <65 years of age if the vaccine was administered >5 years ago. Other indications for repeat vaccination include nephrotic syndrome, chronic renal disease, and other immunocompromised states, such as after transplantation. Annually, Perform an annual test for the presence of microalbuminuria in microalbumin/creatinine Type 1 diabetes patients with diabetes duration of 5 years and in all Type 2 diabetes patients, starting at diagnosis. Dilated eye exam Patients with Type 1 diabetes should have an initial dilated and (by Ophthalmology or Optometry) comprehensive eye examination within 3–5 years after the onset of diabetes. Patients with Type 2 diabetes should have an initial dilated and comprehensive eye examination shortly after the diagnosis of diabetes. Subsequent examinations should be repeated, annually. Less frequent exams (every 2–3 years) may be considered with the advice of an eye care professional in the setting of a normal eye exam. Examinations will be required more frequently, if retinopathy is progressing or patient becomes pregnant. Visual exam at every regular visit Annual comprehensive exam (tuning fork, monofilament, palpation of pulses, and visual exam); educate regarding risk and prevention. Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Diabetes education Evaluate annually Smoking Cessation Counseling Advise all patients not to smoke. Include smoking cessation counseling and other forms of treatment as a routine component of diabetes care. Medical Nutrition Therapy Evaluation at time of diagnosis and annually Screening of ABI recommended for patients >50 years of age who have other PAD risk factors. Diagnostic ABI should be performed in any patient with symptoms of PAD. Other Treatment Modalities
 Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes with a history of CVD  Consider aspirin therapy (75–162 mg/ day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk _10%).  Do not use aspirin in pts. < 21 yr. of age because of the increase risk of Reyes syndrome  Aspirin is not recommended for those at low CVD risk (women under age 60 years and men under age 50 years with no major CVD risk factors; 10-year CVD risk under 5%)  Clinical judgment should be used for those at intermediate risk (younger patients with one or more risk factors, or older patients with no risk factors; those with 10-year CVD risk of 5–10%) until further research is available. Service - Other Treatment
Recommended Interval
Modalities
ACE inhibitors (Initial agent of Monitor serum potassium levels and renal function. Titrate dose to choice for hypertensive DM and for minimize urine protein level. non hypertensive type 1 diabetes pts. with microalbuminuria) ARB (Initial agent of choice for Monitor serum potassium levels and renal function. Titrate dose to hypertensive type 2 diabetic pts. minimize urine protein level. with microalbuminuria; or if patient does not tolerate ACEi therapy). Target BP <130/80 or 140/80 Every visit (Patients found to have systolic blood pressure 130 or >140 depending on target or diastolic blood pressure 80 mmHg should have blood pressure confirmed on a separate day, and therapy initiated.) ACE-I & ARBs considered first line agents for Rx; nutritionist consult for review of dietary sodium intake and ‘hidden salt'. Note: This guideline is for reference only and is not intended or designed as a substitute for the reasonable exercise of independent clinical judgment by providers. This guideline is recommended for adults with either insulin dependent or non-insulin dependent diabetes mellitus. Patients younger than 18 years and pregnant females with diabetes are not included. VIII. References
1. ACE/ACCE consensus Statement: Diagnosis and Management of Prediabetes in the Continuum of Hyperglycemia; 2008. Endocrine Practice (14) 7. October 2008. 2. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 and Adjustment of Therapy. Diabetes Care January 2009 vol. 32 no. 1 193-203 3. Standards of Medical Care in Diabetes- 2013, American Diabetes Association. Diabetes Care volume 36, supplement 1, January 2013. 4. Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials. American College of Physicians, Annals of Internal Medicine. Volume 154 • Number 8. April 2011 5. AACE Guidelines (American Association of Clinical Endocrinology) Medical Guideline for Clinical Practice For Developing A Diabetes Mellitus Comprehensive Care Plan. Endocrine Practice (Vol 17) March/April 2011. Management of Adult Diabetes Mellitus Clinical Practice Guideline initiated 1997. Clinical Guidelines are reviewed every two years by a committee of experts in the field. Updates to guidelines occur more frequently as needed when new scientific evidence or national standards are published. IX. Attachments
Oral Diabetes Agents (pages 7-13) Insulin's and injectables (page 13 & 15) Algorithm- Metabolic Management of Type 2 Diabetes (page 16) Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 (Attachment I)
ORAL DIABETES AGENTS
Class/Agent
Primary Action
Efficacy
Typical Dose
Side Effects
Sulfonylureas
glyburide (Glynase ,
Glynase : 0.75-12mg/day; max 12mg/day (divide hypoglycemia, weight gain, GI upset release of insulin from the pancreas HbA1c:  1.5-2% glyburide: 1.25-20mg/day; max 20mg/day (divide Precautions
hepatic/renal impairment glipizide (Glucotrol , glipizide: 5-40mg/day 30 min. prior to meals; max glyburide implicated in negative outcomes post-MI 40mg/day (divide doses >15mg) Empty Glucotrol XL tablet shell may appear in stool Glucotrol XL : 5-10mg/day with breakfast; max Glyburide is not recommended for
CrCl<50ml/min; Glipizide ok for
glimepiride: 1-4mg/day with breakfast; max 8mg/day CrCl<10ml/min; Glimepiride ok for
Biguanides
metformin
500mg/day with a meal increasing slowly by 500mg nausea, diarrhea; often resolve after 2-3 weeks of use. q 2 weeks; max 2550mg/day (2-3 times a day dosing Precautions
HbA1c:  1.5-2% is more effective and better tolerated) Do not administer at the time of or for 48 hours after improves insulin  TG, LDL, Chol procedures involving intravascular iodinated contrast Available in Liquid Glucophage XL : 500mg/day with evening meal media and resume therapy only when normal renal form, Riomet® , increasing by 500mg weekly; max 2000mg once function returns. Avoid in patients with frequent alcohol contains 500 mg of daily (if 2000mg/day ineffective, may try 1000mg use, or liver or kidney disease due to increased risk of twice a day or switch to regular release metformin on lactic acidosis. hydrochloride per 5 a mg-per-mg basis) Contraindicated in patients with
SCr >1.4 (female) or SCr >1.5
Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Alpha-Glucosidase Inhibitors
acarbose (Precose ) FPG: little effect acarbose: 25mg three times a day with the first bite abdominal pain, diarrhea, bloating, flatulence,  LFTs HbA1c:  0.5-1% of each main meal increasing to 50mg three times a (with acarbose only) miglitol (Glyset ) PPG:  50mg/dl day and then 100mg three times a day after 4-8 weeks; max 100mg three times a day if patient is Precautions
thereby lowering >60kg and 50mg three times a day if <60kg not recommended for patients with SCr>2mg/dl. Asymptomatic / reversible increases in AST and/or ALT hypoglycemia – miglitol: 25mg three times a day with the first bite of has occurred in up to 14% of acarbose-treated patients. sucrose products each main meal increasing to 50mg three times a Fulminant hepatitis –rare. day after 4-8 weeks and 100mg three times a day Contraindicated in patients with
after 3 months; max 100mg three times a day inflammatory bowel disease, colonic
ulceration, or intestinal obstruction.
Sulfonylurea + Biguanide
metformin +
FPG:  50mg/dl Glucovance
hypoglycemia, weight gain, diarrhea, GI upset release of insulin initial treatment: 1.25/250mg once or twice daily with meals and increase by 1.25/250mg every 2 weeks; Precautions
max 10/2000mg/day Do not administer at time of or for 48 hours after metformin + glipizide procedures involving intravascular iodinated contrast previously treated patients: 2.5/500-5/500mg twice media and resume therapy only when normal renal peripheral tissues a day with meals and increase by 5/500mg; max function returns. Avoid in patients with frequent alcohol use, or liver or kidney disease due to increased risk of lactic acidosis. Bioequivalence has not been established for glyburide implicated in negative outcomes post-MI metformin and glyburide in comparison with Glucovance therefore, metformin and Contraindicated in patients with SCr >1.4
glyburide should not be substituted for (female) or SCr >1.5 (male)
Metaglip
initial treatment: 2.5/250mg daily – 2.5/500mg twice a day with meals and increase by 1 tablet daily every 2 weeks; max 10/2000mg daily previously treated patients: 2.5/500 – 5/500mg twice a day with meals and increase in increments no to exceed 5/500mg; max 20/2000mg daily The starting dose should not exceed the current dose of metformin or glipizide already being taken Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Thiazolidinediones
pioglitazone (Actos )
Improves insulin pioglitazone: 15-45mg once daily; max 45mg/day edema, weight gain, hypoglycemia, diarrhea,  LFTs Precautions
rosiglitazone: 4mg/day in single or divided doses and Not recommended for patients with NYHA class III or IV peripheral glucose  LDL, Chol, HDL increase to 8mg/day in single or divided doses after heart failure, CYP450 drug interactions, or with history  If patient is stable on medication continue at lower dosage and continue to monitor. Due to cardiovascular risks, rosiglitazone-
containing medications are only available
Check LFTs at baseline and periodically
through the Avandia-Rosiglitazone Medicines
thereafter. D/C if LFTs>3x upper limit of
Access Program

Rosiglitazone not approved for use with insulin
because of increased risk of edema, CHF, and
possibly MI

Thiazolidinedione + Sulfonylurea
Pioglitazone +
Improves insulin edema, weight gain, hypoglycemia, diarrhea,  LFTs. Glimepiride
May cause or exacerbate heart failure. (Duetact)
Initial dose should be based on current dose of Not recommended in any patient with symptomatic peripheral glucose pioglitazone and/or sulfonylurea. heart failure; initiation contraindicated with NYHA class III or IV heart failure release of insulin Patients inadequately controlled on glimepiride
from the pancreas alone: Initial dose: 30 mg/2 mg or 30 mg/4 mg once daily Patients inadequately controlled on pioglitazone
alone: Initial dose: 30 mg/2 mg once daily
Maximum dose: Pioglitazone 45 mg/glimepiride 8 mg daily Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Thiazolidinedione + Sulfonylurea

Improves insulin Avandaryl:
Precautions
Rosiglitazone +
Not recommended for patients with NYHA class III or IV Glimepiride
Initial: Rosiglitazone 4 mg and glimepiride 1 mg once heart failure, CYP450 drug interactions, or with history (Avandaryl)
peripheral glucose daily or rosiglitazone 4 mg and glimepiride 2 mg
once daily (for patients previously treated with If patient is stable on medication continue sulfonylurea or thiazolidinedione monotherapy) at lower dosage and continue to monitor. release of insulin from the pancreas hypoglycemia, weight gain, GI upset Patients switching from combination rosiglitazone and glimepiride as separate tablets: Use current Due to cardiovascular risks, rosiglitazone-
dose. Maximum: Rosiglitazone 8 mg and glimepiride 4 mg once daily containing medications are only available through
the Avandia-Rosiglitazone Medicines Access
Titration:Dose adjustment in patients previously on sulfonylurea monotherapy: May take 2 weeks to observe decreased blood glucose and 2-3 months to see full effects of rosiglitazone component. If not adequately controlled after 8-12 weeks, increase daily dose of rosiglitazone component. Maximum: Rosiglitazone 8 mg and glimepiride 4 mg once daily Dose adjustment in patients previously on thiazolidinedione monotherapy: If not adequately controlled after 1-2 weeks, increase daily dose of glimepiride component in ≤2 mg increments in 1-2 week intervals. Maximum: Rosiglitazone 8 mg and glimepiride 4 mg once daily) Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Thiazolidinedione + Biguanide
rosiglitazone +
Improves insulin Prior Therapy (metformin) Avandamet Dose edema, weight gain, hypoglycemia, diarrhea,  LFTs, 1000mg/day 2mg/500mg twice a day nausea, diarrhea decreases hepatic 2000mg/day 2mg/1000mg twice a day Precautions
Prior Therapy (Avandia) Avandamet Dose CYP450 drug interactions temporarily discontinue 48 4mg/day 2mg/500mg twice a day hours prior to procedures involving intravascular 8mg/day 4mg/500mg twice a day iodinated contrast media or surgery and resume therapy only when normal renal function returns. Avoid in patients with frequent alcohol use, or liver or kidney metformin (Actoplus Initial dose should be based on current dose of disease due to increased risk of lactic acidosis. pioglitazone and/or metformin; daily dose should be Check LFTs at baseline and periodically
divided and given with meals thereafter. D/C if LFTs>3x upper limit of
Patients inadequately controlled on metformin
alone: Initial dose: Pioglitazone 15-30 mg/day plus
current dose of metformin Patients inadequately Contraindicated in patients with SCr >1.4
controlled on pioglitazone alone: Initial dose:
(female) or SCr >1.5 (male) and in patients
Metformin 1000-1700 mg/day plus current dose of Note: When switching from combination
pioglitazone and metformin as separate tablets: Use current dose. Dosing adjustment: Doses may be increased as
increments of pioglitazone 15 mg and/or metformin 500-850 mg, up to the maximum dose; doses should be titrated gradually. Guidelines for frequency of adjustment (adapted from rosiglitazone/metformin combination labeling): After a change in the metformin dosage,
titration can be done after 1-2 weeks After a change in the pioglitazone dosage,
titration can be done after 8-12 weeks Maximum dose: Pioglitazone 45 mg/metformin metformin (varied Usual initial dose of Actoplus Met XR: release) (Actoplus metformin 1000 mg and 15 or 30 mg pioglitazone given once daily with evening meal Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Repaglinide: 0.5-2mg 15-30 minutes before each hypoglycemia, weight gain HbA1c:  0.5-2% meal and increase to 4mg with each meal; max 4mg dependent insulin PPG:  50mg/dl per dose and 16mg/day Precaution
nateglinide (Starlix ) hepatic impairment, CYP450 drug interactions Short half-life (1 nateglinide: 60-120mg three times a day 30 minutes hr) – quick onset prior to each meal Dipeptidyl Peptidase IV (DPP-IV) inhibitor
Sitagliptin (Januvia )
HbA1c:  0.5-0.6% 100 mg once daily Dosing in renal dysfunction: Clcr ≥30 to <50 mL/minute: 50 mg once daily Scr: Males: >1.7 to ≤3.0 mg/dL; Females: >1.5 to ≤2.5 mg/dL: 50 mg once daily Clcr<30 mL/minute: 25 mg once daily Scr: Males: >3.0 mg/dL; Females: >2.5 mg/dL: 25 ESRD requiring hemodialysis or peritoneal dialysis: 25 mg once daily; administered without regard to timing of No dosage adjustment required for mild-moderate hepatic impairment. 2.5-5mg once daily Use 2.5mg daily for patients with CrCl <50 ml/min or if on a CYP3A4/5 inhibitor (azole antifungal, protease inhibitor, clarithromycin) Effectiveness of linagliptin is decrease when used in combination with CYP3A4 inducers (rifampin) – use alternative therapy. Acute and chronic pancreatitis have been reported with DPP-IV inhibitor use; monitor for signs/ symptoms of Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 Dipepyl Pepase IV (DPP-IV) Inhibitor + Biguanide
Sitagliptin +
FPG:  50-60mg/dl Initial doses should be based on current dose Avoid metformin in renal dysfunction (SCr >1.5 in males metformin (Janumet) HbA1c:  1.5-2% of sitagliptin and metformin; daily doses should and >1.4 in females)  TG, LDL, Chol be divided and given twice daily with meals. Avoid metformin in hepatic dysfunction Maximum: Sitagliptin 100 mg/metformin 2000 resulting in prolonged Patients inadequately controlled on metformin alone: Initial dose: Sitagliptin 100 mg/day plus current dose of metformin. Note: Per
manufacturer labeling, patients currently receiving metformin 850 mg twice daily should receive an initial dose of sitagliptin 50 mg and improves insulin metformin 1000 mg twice daily Patients inadequately controlled on sitagliptin
alone: Initial dose: Metformin 1000 mg/day plus
sitagliptin 100 mg/day. Note: Patients currently
receiving a renally adjusted dose of sitagliptin
should not be switched to combination product.
Dosing adjustment: Metformin component
may be gradually increased up to the
maximum dose. Maximum dose: Sitagliptin 100
mg/metformin 2000 mg daily
Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 (Attachment II)
INSULINS
Duration
lispro (Humalog )* Insulin aspart (NovoLog ) Insulin glulisine (Apidra) Regular (Humulin R, Novolin R) NPH (Humulin N, Novolin N) Insulin glargine (Lantus ) Insulin detemir (Levemir®) Combination
70/30 (Humulin 70/30, Novolin 70/30) (70% NPH/30% regular) Humalog Mix 75/25 (75% lispro protamine/25% lispro)* Humalog 50/50 (50% lispro protamine/50% lispro)* NovoLog Mix 70/30 (70% insulin aspart protamine/30% insulin aspart)† * Lispro insulin (Humalog ) , Humalog Mix 75/25, and Humalog 50/50 should be given 0-15 minutes before a meal or immediately after a meal † Insulin aspart (NovoLog ) and NovoLog Mix 70/30 should be given 0-10 minutes before a meal ‡ Dosing recommendations for insulin glargine (Lantus ) Switching from once daily NPH to insulin glargine: no change in dosage. Switching from twice a day NPH to insulin glargine: decrease insulin glargine dose by 20% and titrate to patient's response to reduce incidence of hypoglycemia. Insulin glargine should not be mixed with other types of insulin ** Has no pronounced peak Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 OTHER AGENTS
Primary Action
Efficacy
Side Effects
Slows the rate of Type 1 diabetes: initiate postprandial glucose with 15 mcg SC immediately Nausea, diarrhea, vomiting increase by slowing gastric Weight: 1-2kg prior to each main meal and emptying, suppressing increase by 15 mcg glucagons secretion, and increments to 30-60 mcg Contraindications: decreasing food intake Type 2 diabetes: initiate gastroparesis, hypoglycemia through increase in satiety. with 60 mcg SC immediately prior to each main meal and increase to 120 mcg when Do not mix with insulin Reduce preprandial insulin Increase dose only when no doses (rapid and short acting significant nausea has insulin and 70/30, 50/50, 75/25) occurred for 3-7 days Glucose dependent insulin 5mcg SC up to 60 minutes release, lowers glucagon prior to the morning and Nausea, diarrhea, vomiting during hyperglycemia, slows evening meals. After 1 gastric emptying, reduces month, can increase to food intake through increase Can be used in combination in satiety. Secondary effect with metformin, a sulfonylurea, of medication is weight loss or both. May need to reduce or prevention of weight gain sulfonylurea dose. as glucose control improves For use only in type 2 diabetes Anti-exenatide antibodies: Use may be associated with the development of anti-exenatide Cases of acute pancreatitis have been reported Not recommended to be used in patients with gastroparesis or severe gastrointestinal disease. Use not recommended in severe renal impairment (CrCl<30 mL/minute). 2 mg once weekly (may Dose and duration dependent administer missed dose as thyroid C-cell tumors have developed in animal studies with exenatide extended release therapy. Patients should be counseled on the risk and symptoms of thyroid tumors 0.6mg SC daily x 1 week, Contraindicated in patients with then 1.2mg SC daily. May a personal or family history of increase to 1.8mg SC daily. medullary thyroid cancer or Allow at least 1 week in Multiple Endocrine Neoplasia between dose increases. Syndrome type 2. Given independent of meals. Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013 (Attachment III)
Algorithm for the metabolic management of type 2 diabetes
Reinforce lifestyle intervention at every visit. Check A1C every 3 months until <7% and then at least every 6 months. The interventions should be changed if A1C is < 7% .asulfonylureas other than glubenclamide (glyburide) or chlororpamide. bInsufficent clinical use to be confident regarding safety. Diabetes Care, January 2009. vol 32 no.1. 193-203) Management of Adult Diabetes Mellitus Copyright MedStar Health, 2013

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