MedicineLakex

 

Referral

SUTTER MEDICAL FOUNDATION (SMF)
2800 L Street, 7th Floor Sacramento, CA 95816 SMF PCP Treatment & Referral Guideline
for Type 2 Diabetes Mellitus
Developed July 26, 2006 Revised September, 2011 Diabetes Type 2 .Page 1 Type 2 Diabetes Adult Outpatient Insulin Guidelines………………Page 2 Type 2 Diabetes: Byetta (Exenatide) Guideline…………………….Page 8 Type 2 Diabetes: Victoza (Liraglutide) Guideline………………….Page 9 Diabetes Medicines – Titration Table……………………………….Page 10 SPA PCP Treatment & Referral Guideline – Type 2 Diabetes Developed 7/26/06 Page 2 of 2 Type 2 Diabetes
A "one time" consultation to the endocrinologist with return to PCP for ongoing care is applicable, if all of the following have been met before a consult request is made. The PCP actively works with the patient and consistently sets the expectation that the PCP and the pt will work together to improve and control diabetes. This implies that patients are routinely scheduled with the PCP offices; at least quarterly, to monitor progress, review home testing results and go over lab results. PCPs let the pts know an Endocrine consult is a one time opinion to help the PCP manage the diabetes and pts are encouraged to make a follow up appt with the PCP shortly after the consultation to go over the recommendations. Patients have been actively managed in the PCP practice with at least three (3) visits 6-12 weeks apart where lifestyle modification, blood sugar results and medication changes have been applied. These recommendations and med changes need to be clearly documented in the medical record A) Patients have tried all categories of drugs in combination unless medically contraindicated. This includes: a) Insulin secretagogues c) Thiazolidinediones B) Patients have been seen by the Diabetes Education Team within the previous 12 mos and worked with the education team on the treatment protocols in place. These include the oral medicine titrations and the insulin guidelines. C) Patients are actively involved in their care and willing to check their blood sugar a minimum of twice a day, while working on portion control and exercise. APPROVAL:
SMF Medical Director _December 14, 2011 Date Approval / Revision Summary:
SMF QM/UM Committee
Date: _12/14/2011 _ SPA Steering Committee Type 2 Diabetes Adult Outpatient Insulin Guidelines
Sutter Medical Foundation. May 2011.
GENERAL RECOMMENDATIONS
• Start insulin if A1C and glucose levels are above goal despite optimal use of other diabetes
medications. (Consider insulin as initial therapy if A1C very high, such as > 10.0%) 6,7,8
• Start with BASAL INSULIN for most patients 6,7,8
• Consider the following goals1,6
ADA A1C Goals:
A1C < 7.0 for most patients
A1C > 7.0 (consider 7.0-7.9) for higher risk patients 1. History of severe hypoglycemia 2. Multiple co-morbid conditions
3. Long standing diabetes 4. Limited life expectancy
5. Advanced complications or 6. Difficult to control despite use of insulin
ADA Glucose Goals*: Fasting and premeal glucose < 130
Peak post-meal glucose (1-2 hours after meal) < 180
Difference between premeal and post-meal glucose < 50
*for higher risk patients individualize glucose goals in order to avoid hypoglycemia
BASAL INSULIN

Detemir (Levemir®) NPH Note: NPH insulin has elevated risk of hypoglycemia so use with extra caution6,8,15,17,25,32
• Basal insulin is best starting insulin choice for most patients (if fasting glucose above goal). 6,7,8
• Start one of the intermediate-acting or long-acting insulins listed above. 6,7 Start insulin at night. 8
• When starting basal insulin: Continue secretagogues. Continue metformin. 7,8,20,29
• Note: if NPH causes nocturnal hypoglycemia, consider switching NPH to long-acting insulin. 17,25,32
STARTING DOSE:
Start dose: 10 units6,7,8,11,12,13,14,16,19,20,21,22,25
Consider using a lower starting dose (such as 0.1 units/kg/day32) especially if
patient is thin or has a fasting glucose only minimally above goal.17,19
TITRATION
Teach patient to self titrate ↑ by 1 units every 1 day until average fasting glucose < 130*16
(*Inform patient to hold titration until further evaluation if develops any hypoglycemia)
Titrate 1 time per week as per table below until average fasting glucose < 13010,11,13,14,15,17,18,20,21,26,28
Fasting glucose > 180 increase 8u Fasting glucose 160-180 increase 6u Fasting glucose 140-160 increase 4u Fasting glucose 130-140 increase 2u Fasting glucose 70-130 no change Fasting glucose < 70 decrease 2u or 10% Within one to two months,
evaluate post-meal glucose
If post-meal glucose levels > 50 mg/dl above premeal: consider ADD PRANDIAL INSULIN6,7,8
Type 2 Diabetes
Note: If patient unable to do multiple daily injections, consider switching to MIXED INSULIN instead of adding
Prandial Insulin
prandial insulin (see pg. 3 for switching to mixed insulin).. (Mixed insulin is more likely to cause
Guideline
hypoglycemia8,19 and generally requires a fixed meal schedule8) Sutter Medical Foundation. May 2011 Page 1 of 6 PRANDIAL INSULIN
Rapid Acting: Lispro (Humalog®)
Aspart (Novolog®)
Glulisine (Apidra®)
Short Acting: Regular Note: Regular insulin has longer peak and extra risk of hypoglycemia so use with caution6,8,33
• Add prandial insulin to basal insulin if post-meal blood glucose levels are above goal.6,7,8
• Start one of the prandial insulins listed above. 6,7
• When adding prandial insulin: Stop secretagogues. Continue metformin. Continue basal insulin (may need to re-adjust dose).6,7,8
• Give rapid acting insulins less than 15 minutes before meal. Give Regular insulin 30 minute before meals.5,7
• Note: after maximizing prandial and night-time basal insulin dose, may need to consider adding a morning dose of basal insulin if
) 18,19,26,28,30
re-dinner lucose remains above oal more likel to be necessar if usin NPH
STARTING DOSE:
ALTERNATE STARTING DOSE:
4 units qAC6,35,36,37
1 unit to 15 grams carbs qAC34
if meals vary in
Alternative dose:
size and patient is
Note: may consider calculate insulin to carb (I:C) ratio = 7-10% of basal insulin dose qAC7,8,36 accurate at
500 / total daily dose (TDD) of insulin (500 rule)7
counting carbs
• May also consider add I:C ratio to snacks • Instruct patients to eat carb consistent meals when first starting prandial insulin. • May consider start prandial insulin with largest meal Consider adding pre-meal Correction Factor (CF) 7:
only6,7 (if so, may consider postpone stopping secretagogue until using prandial insulin for 2 or more meals per day) Add 1 unit for each 50 that pre-meal glucose is > 130
Note: if on NPH bid, may hold lunch time prandial dose Alternative method to determine pre-meal correction factor:
Correction factor (CF) = 1800 / total daily dose of insulin (1800 rule)
*May also consider correction factor at bedtime using target of 150
Consider adding pre-meal Correction Factor (CF) 7:
Add 1 unit for each 50 that pre-meal glucose is > 130
Alternative method to determine pre-meal correction factor:
Adjust insulin to carb ratio as appropriate per
Correction factor (CF) = 1800 / total daily dose of insulin (1800 rule)
below until post-meal glucose <1807,34
*May also consider correction factor at bedtime using target of 150 If post-meal pattern low If post-meal pattern high TITRATE:
Back up the scale Move down the scale Titrate1-2 units every 2-3 days
until post-meal glucose < 1806,8,34,35
Alternate adjustment:
(May consider different doses for different meals) Adjust insulin to carb ratio per 500 rule7 MIXED INSULIN
75/25 Lispro Mix (Humalog® Mix) or 50/50 Lispro Mix (Humalog® Mix)
70/30 Aspart Mix (Novolog ®Mix)
70/30 NPH/Regular Note: 70/30 NPH/Regular insulin has elevated risk of hypoglycemia so use with extra caution6,8
• Mixed insulin is an option for patients who are unable to do multiple injections and who have fixed meal schedules.8
• Mixed insulin is more likely to cause hypoglycemia compared to basal and prandial insulins.8,19
• Start one of the mixed insulins listed above.
• When starting mixed insulin: Stop secretagogues. Continue metformin. (If already on other insulin, then see guideline for
switching to mixed insulin on page 3) . 7,8
STARTING DOSE:
TITRATE:
PRE-DINNER dose 6-10 units40,43,45,50
Titrate1-2 units every 2-3 days until average target
(may adjust depending on previous basal insulin dose42,51)
glucose <13043,51
Target glucose for titration is fasting glucose. 8,43,45,46,53
(may also consider post-dinner glucose when titrating dose) Titrate 1-2 times per week such as per table below until
average target glucose <13043
• Target glucose >200
↑ by 4 units
STARTING DOSE:
• Target glucose 131-200 ↑ by 2 units
PRE-BREAKFAST dose: 6-10 units40,43,45,50
• Target glucose 70-130 No change
(may adjust depending on previous basal insulin dose42,51)
• Target glucose < 70
↓ 2-4 units or by 10%
Target glucose for titration is pre-dinner glucose. 8,43,45,46,53
• May require different doses for pre-breakfast and pre-dinner (may also consider post-breakfast glucose when titrating dose) • May consider adding pre-lunch dose as well if needed42,53 Sutter Medical Foundation. May 2011 Page 2 of 6 Switching Mixed Insulin to Basal/Prandial Insulin
Selection of Patients:
• Patient has persistant hypoglycemia episodes or
• Patient has excess glucose variability or
• Patient wants a more flexible meal schedule
• Determine total daily mixed insuiln dose (TDD) Starting dose of prandial insulin:
• Stop mixed insulin 10% TDD (total daily mixed insulin dose) qAC
Start basal insulin qHS and prandial insuiln qAC. Note: This is essential y = to the current prandial component of mixed insulin
Starting dose of basal insulin:
50% TDD (total daily mixed insulin dose) qHS
Note: This is essentially = to 80% of the current basal component
PRANDIAL Insulin of mixed insulin Switching from Basal or Basal/Prandial Insulin to Mixed Insulin
Selection of Patients:
• Difficulty taking multiple injections daily
• Stable consistent meal schedule
• Stable glucose pattern and no hypoglycemia episodes
Starting dose of dinner dose:
• Determine total daily insulin dose (TDD) 30-40% of total daily insulin dose
Stop both Basal and Prandial insulin • Start Mixed insulin before breakfast and before dinner. Target glucose for titration is fasting glucose. 8,43,45,46,53
(may also consider post-dinner glucose when titrating dose)
Starting dose of breakfast dose:
30-40% of total daily insulin dose
Target glucose for titration is pre-dinner glucose. 8,43,45,46,53
(may also consider post-breakfast glucose when titrating dose) Switching Insulin Types
Switching from NPH to Lantus/Levemir: consider if patient has nocturnal hypoglycemia or persistent day time hyperglycemia:
Start Lantus/Levemir before bed at 50%-70% of total daily NPH dose* (then titrate per basal insulin guideline) Switching from Lantus/Levemir to NPH: consider if patient needs to switch due to cost
Start NPH before bed at 40% of total daily Lantus/Levemir dose* (then titrate per basal insulin guideline) Caution: • Watch for nocturnal hypoglycemia • Evaluate day time glucose levels. If necessary consider add morning NPH dose as well. • If adding morning NPH dose, consider lower lunch prandial insulin due to midday NPH peak Switching from Regular to Humalog/Novolog/Apidra: consider if patient has day time hypoglycemia
Start Humalog/Novolog/Apidra at 80% of current Regular Insulin mealtime dose* (then titrate per prandial insulin guideline) Switching from Humalog/Novolog/Apidra to Regular Insuiln: consider if patient needs to switch due to cost
Start Regular Insulin at 80% of current mea ltime Humalog/Novolog/Apidra dose* (then titrate per prandial insulin guideline) Caution: • Watch for day time hypoglycemia • Need to take Regular Insulin injection 30 minutes before meals *NOTE: consider alternate dose adjustment if low or high glucose levels on current insulin dose!
Pre-Operative Diabetes Guidelines
Day before surgery: Take all regular diabetes pil s and oral medications (except hold evening metformin dose). Take Byetta,
Victoza and Symlin as usual. Day of surgery*: Hold all regular diabetes pills and oral medications. Hold Byetta, Victoza and Symlin.
*Tell patient to treat any hypoglycemia with 15 gms of glucose gel or glucose tabs or 4 ozs of clear juice such as apple or cranberry.
Adjusting Insulin
Day before surgery: Morning of surgery: Take 80% of usual nighttime dose* Basal Insulin: If patient regularly takes basal insulin in the Prandial Insulin: Take as usual morning, take 80% of usual morning dose* Take 80% of usual nighttime dose* Prandial Insulin: Hold
Mixed Insulin:
*NOTE: may consider alternate dose adjustment if low or high glucose levels on current insulin dose!
Sutter Medical Foundation. May 2011 Page 3 of 6 ADDITIONAL INFORMATION:
Alternate self titration for basal insulin6,7,8,13,14,30,32:
May consider self titrating basal insulin by increasing dose 2 unit every 2-3 days until average fasting glucose is < 130. Self titration of 2 unit intervals may be easier for patients using insulin syringes. Other diabetes medication in combination with insulin6,7,8,20,24,29
Metformin Continue if able because helps prevent weight gain when patient on insulin
Secretagogues: (sulfonylureas and meglitinides): Consider continuing when patient is on basal insulin only. Stop when
patient is on prandial or mixed insulin. Other Diabetes Medications: decision to continue or discontinue other diabetes medications should be made with consideration of multiple individual patient characteristics. Note: once patient's glucose levels are controlled with insulin, it may occasional y be possible to stop insulin and continue or
switch to oral medications depending of the stage of the diabetes and changes in other individual patient characteristics.6,7,8
Example of correction factor using 1800 Rule7
Patient on 60 units basal insulin. Total Daily Dose (TDD) is 60 units. Correction Factor (CF) = 1800 / 60 = 30. If pre-meal glucose = 230, blood glucose is 150 mg/dl above goal of 130; Correction is 150/30 = 5 units. Give 5 units in addition to prandial insulin dose being used to cover meal. Example of Insulin with prandial dose of 4 units and correction factor of 1:50, correcting down to 130
Pre-meal Glucose Level Prandial Insulin Dose Example of carbohydrate ratio using 500 Rule7
Patient on 50 units basal insulin daily. Total Daily Dose (TDD) is 50 units. Insulin to Carbohydrate Ratio (I:C Ratio): 500/50 = 1:10 units. For a 60 gm carbohydrate meal = 60/10 = take 6 units. Mealtime Advice2,5
Take rapid acting prandial and mixed insulins just before a meal. At restaurants only take once food actually arrives at table. Take Regular insulin 30 minutes before meals. Tell patient to carry rapidly absorbed carbohydrate source at all times and teach friends and family about how to treat low
glucose. Treat low glucose (<70) as per Rule of 15's: Give 15 gm of rapidly absorbed carbohydrate (ie: 1/2 cup juice or 4
glucose tabs). Recheck glucose level in 15 minutes. Give another 15 gm of carbohydrate if glucose still < 70. Repeat until
the glucose level higher than 70. Once glucose level returns to normal, consider follow with a snack or meal. Inform provider
of hypoglycemia episodes at next appointment. If severe (unconscious, seizures) call 911 and give glucagon (1.0 for adult,
0.5 for child < 50 lbs) if available. Prescribe glucagon kit for high risk patient to have at home.
Carry personal ID and wear medical ID. Insulin Device
Consider insulin pen if able for patients with vision, dexterity or cognition difficulties or for patient convenience. Note insulin pens cost more than insulin vials. However, total cost of insulin pen is potentially lower than vial if patient's daily insulin dose is low (since less unused insulin needs to be discarded at end of month). Insulin pens may not be covered by insurance. Storage2,5
Refrigerate insulin until opened. Discard after expiration date. Once opened can be kept at room temperature. Avoid heat. Replace insulin vial or pen as required per specific insulin package insert. Syringes and Needles2,4
For pen consider use pen needles that are 31or 32 gauge and 5 mm to 8 mm. For vials consider use syringes that are 0.3-1.0 cc with ultrafine 5/16" 31 gauge needles. Instruct patient to leave needle in skin for 5 or more seconds after injection completed. Exercise9
Low glucose levels may occur during or after exercise. Carry glucose source when exercising. Check glucose before and during exercise. If patient has low glucose levels associated with exercise: consider decreasing preceding prandial insulin dose (if within several hours before exercise) and/or taking extra carbohydrates before or during exercise. All patients should receive Diabetes Self Management Training (DSMT) and Medical Nutrition Therapy (MNT) by certified diabetes educator if possible. Sutter Medical Foundation. May 2011 Page 4 of 6 LITERATURE SEARCH AND RATING PROCESS
The identification and rating of the body of evidence to support the Type 2 Diabetes Insulin Guidelines followed a three-step process: 1. Pertinent articles for review were by identified by a Medline search including the key words: Diabetes Mellitus, Type 2/drug therapy, Hypoglycemic Agents, Insulin, Algorithms, Titrate, Titration, Bolus, and Basal. The search was limited to 2005-2010 and the language English. Older clinical trials evaluating Regular insulin were included, since none were available from 2005-2010. The most recent ADA and AACE consensus statements, position statements and technical reviews on diabetes care topics were also identified. Insulin package insert recommendations were obtained from Lexi-Comp, Online. 2. Experts in diabetes care then examined the list of articles and included only those that were identified as randomized controlled clinical trials examining the initiation and titration of insulin, the most recent general consensus statements, technical reviews, or position statements by ADA and AACE, the most recent insulin review article by the American Academy of Family Practice, and the Lexi-Comp online insulin package insert recommendations. 3. The articles were reviewed and the body of evidence was rated using a system adopted from the ADA grading system for clinical practice recommendations. American Diabetes Association Standards of medical care in diabetes--2010. Diabetes Care. 2010 Jan;33 Suppl 1:S12. (A) Clear evidence from well-conducted, generalizable, randomized control ed trials that are adequately powered, including:
Evidence from a well-conducted multicenter trial Evidence from a meta-analysis that incorporated quality ratings in the analysis Compelling non-experimental evidence, i.e., "all or none" rule developed by Center for Evidence Based Medicine at Oxford Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including: Evidence from a well-conducted trial at one or more institutions Evidence from a meta-analysis that incorporated quality ratings in the analysis (B) Supportive evidence from well-conducted cohort studies:
Evidence from a well-conducted prospective cohort study or registry Evidence from a well-conducted meta-analysis of cohort studies Supportive evidence from a well-conducted case-control study Supportive evidence from poorly controlled or uncontrolled studies Evidence from randomized clinical trials with one or more major or three ormore minor methodological flaws that could invalidate the results Evidence from observational studies with high potential for bias (such as case series with comparison to historical controls) Evidence from case series or case reports Conflicting evidence with the weight of evidence supporting the recommendation Expert consensus or clinical experience GENERAL INFORMATION: Consensus Statements and Reviews
1. American Diabetes Association Standards of medical care in diabetes--2010. Diabetes Care. 2010 Jan;33 Suppl 1:S11-61. 2. American Diabetes Association. Insulin administration. Diabetes Care. 2004 Jan;27 Suppl 1:S106-9. 3. Cryer PE, et al. Hypoglycemia in diabetes. Diabetes Care. 2003 Jun;26(6):1902-12. 4. Hofman PL, et al. Defining the ideal injection techniques when using 5-mm needles in children and adults. Diabetes Care. 2010 Sept;33:1940-1944. 5. Lexi-Comp, Online. Lexi-Comp, Inc. 1100 Terex Road, Hudson, OH 4. August 2010. 6. Nathan DM, et al. American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. 7. Ripsin CM, et al. Management of blood glucose in type 2 diabetes mellitus. Am Fam Physician. 2009 Jan 1;79(1):29-36 8. Rodbard HW, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009 Sep-Oct;15(6):540-59. 9. Sigal RJ, et al. Physical activity/exercise and type 2 diabetes. Diabetes Care. 2004 Oct;27(10):2518-39.
BASAL INSULIN (A-level evidence)
10. Bergenstal RM, et al. Adjust to target in type 2 diabetes: comparison of a simple algorithm with carbohydrate counting for adjustment of mealtime insulin glulisine. Diabetes Care. 2008 Jul;31(7):1305-10. 11. Bretzel RG, et al. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008 Mar 29;371(9618):1073-84. 12. Buse JB, et al. DURAbility of basal versus lispro mix 75/25 insulin efficacy (DURABLE) trial 24-week results: safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes. Diabetes Care. 2009 Jun;32(6):1007-13. 13. Davies M, et al. ATLANTUS Study Group. Improvement of glycemic control in subjects with poorly controlled type 2 diabetes: comparison of two treatment algorithms using insulin glargine. Diabetes Care. 2005 Jun;28(6):1282-8. 14. Davies M, et al. AT.LANTUS Study Group. Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial. Diabetes Obes Metab. 2008 May;10(5):387-99. 15. Fajardo Montañana C, et al. Less weight gain and hypoglycaemia with once-daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight Type 2 diabetes patients: the PREDICTIVE BMI clinical trial. Diabet Med. 2008 Aug;25(8):916-23. 16. Harris S, et al. Can family physicians help patients initiate basal insulin therapy successfully?: randomized trial of patient-titrated insulin glargine compared with standard oral therapy: lessons for family practice from the Canadian INSIGHT trial. Can Fam Physician. 2008 Apr;54(4):550-8. 17. Hermansen K, et al. Home P. A 26-week, randomized, paral el, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006 Jun;29(6):1269-74. Erratum in: Diabetes Care. 2007 Apr;30(4):1035. 18. Hollander P, et al. A 52-week, multinational, open-label, paral el-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes. Clin Ther. 2008 Nov;30(11):1976-87. 19. Holman RR, et al. 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009 Oct 29;361(18):1736-47. 20. Janka HU, et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care. 2005 Feb;28(2):254-9. 21. Kennedy L, et al. GOAL AIC Team. Impct of active versus usual algorithmic titration of basal insulin and point-of-care versus laboratory measurement of HbA1c on glycemic control in patients with type 2 diabetes: the Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) trial. Diabetes Care. 2006 Jan;29(1):1-8. 22. Liebl A, et al. PREFER Study Group. Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab 2009 Jan;11(1):45-52. Sutter Medical Foundation. May 2011 Page 5 of 6 BASAL INSULIN (A-level evidence), continued
23. Masuda H, et al. Comparison of twice-daily injections of biphasic insulin lispro and basal-bolus therapy: glycaemic control and quality-of-life of insulin-naïve type 2 diabetic patients. Diabetes Obes Metab. 2008 Dec;10(12):1261-5. 24. Meneghini L, et al. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes--results of the randomized, controlled PREDICTIVE 303 study.Diabetes Obes Metab. 2007 Nov;9(6):902-13. 25. Philis-Tsimikas A, et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther. 2006 Oct;28(10):1569-81. 26. Raskin P, et al. Comparison of insulin detemir and insulin glargine using a basal-bolus regimen in a randomized, controlled clinical study in patients with type 2 diabetes. Diabetes Metab Res Rev. 2009 Sep;25(6):542-8. 27. Robbins DC et al. Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2007 Nov;29(11):2349-64. 28. Rosenstock J, et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose- lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia. 2008 Mar;51(3):408-16. 29. Schiel R, et al. Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study. Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):58-64. 30. Swinnen SG, et al. Rationale, design, and baseline data of the insulin glargine (Lantus) versus insulin detemir (Levemir) Treat-To-Target (L2T3) study: A multinational, randomized noninferiority trial of basal insulin initiation in type 2 diabetes. Diabetes Technol Ther. 2009 Nov;11(11):739-43. 31. Swinnen, SG A 24-week randomized , treat-to-target trial comparing initation of insulin glargine once-daily with insulin detemir twice daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowring drugs. Diabetes Care 2010: 33(6): 1176-1178. 32. Wang XL, et al. Evaluation of the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system.Diabetes Res Clin Pract. 2007 Apr;76(1):30-6. PRANDIAL INSULIN (A-level evidence)
33. Anderson J H; Brunelle R L; Koivisto V A; Pfutzner A; Trautmann M E; Vignati L; DiMarchi R Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group. Diabetes Feb 1997 46 (2) p265-70. 34. Bergenstal RM, et al. Adjust to target in type 2 diabetes: comparison of a simple algorithm with carbohydrate counting for adjustment of mealtime insulin glulisine. Diabetes Care. 2008 Jul;31(7):1305-10. 35. Bretzel RG, et al. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008 Mar 29;371(9618):1073-84. 36. Holman RR, et al. 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009 Oct 29;361(18):1736-47. 37. Lankisch MR, et al. Orals Plus Apidra and LANTUS (OPAL) study group. Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs. Diabetes Obes Metab. 2008 Dec;10(12):1178-85 38. Liebl A, et al. PREFER Study Group. Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab 2009 Jan;11(1):45-52. 39. Masuda H, et al. Comparison of twice-daily injections of biphasic insulin lispro and basal-bolus therapy: glycaemic control and quality-of-life of insulin-naïve type 2 diabetic patients. Diabetes Obes Metab. 2008 Dec;10(12):1261-5. MIXED INSULIN (A-level evidence)
40. Buse JB, et al. DURAbility of basal versus lispro mix 75/25 insulin efficacy (DURABLE) trial 24-week results: safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes. Diabetes Care. 2009 Jun;32(6):1007-13. 41. Clements MR, et. al. Improved glycaemic control of thrice-daily biphasic insulin aspart compared with twice-daily biphasic human insulin; a randomized, open- label trial in patients with type 1 or type 2 diabetes. Diabetes Obes Metab. 2008 Mar;10(3):229-37. 42. Garber AJ, et al. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab. 2006 Jan;8(1):58-66. 43. Holman RR, et al. 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009 Oct 29;361(18):1736-47. 44. Jacober SJ, et. al. A comparison of intensive mixture therapy with basal insulin therapy in insulin-naïve patients with type 2 diabetes receiving oral antidiabetes agents. Diabetes Obes Metab. 2006 Jul;8(4):448-55. 45. Janka HU, et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care. 2005 Feb;28(2):254-9. 46. Liebl A, et al. PREFER Study Group. Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab 2009 Jan;11(1):45-52. 47. Malone JK, et. al. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in bet er overall glycaemic control in patients with Type 2 diabetes. Diabet Med. 2005 Apr;22(4):374-81 48. Masuda H, et al. Comparison of twice-daily injections of biphasic insulin lispro and basal-bolus therapy: glycaemic control and quality-of-life of insulin-naïve type 2 diabetic patients. Diabetes Obes Metab. 2008 Dec; 10(12):1261-5. 49. Miyashita Y, et. al. Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure. Cardiovasc Diabetol. 2008 May 50. Oyer DS, et al. INITIATEplus Study Group. A(1c) control in a primary care setting: self-titrating an insulin analog pre-mix (INITIATEplus trial). Am J Med. 2009 Nov;122(11):1043-9. 51. Robbins DC, et al. Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2007 Nov;29(11):2349-64. 52. Schiel R, et. al. Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study. Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):58-64. 53. Yang W, et al. Biphasic insulin aspart 30 three times daily is more effective than a twice-daily regimen, without increasing hypoglycemia, in Chinese subjects with type 2 diabetes inadequately controlled on oral antidiabetes drugs. Diabetes Care. 2008 May;31(5):852-6. Sutter Medical Foundation. May 2011 Page 6 of 6 Selection of Patients
HbA1c > 7% and
Not on insulin No significant gastroparesis, severe GI disease, severe nausea, or history or risk of pancreatitis. Not recommended in ESRD or severe renal impairment (CrCl < 30 mL/min); use cautiously in renal transplantation. Start Byetta® (exenatide) 5 mcg BID SQ
Administer within 60 min prior to morning and evening meal (or prior to the 2 main meals of the day, approximately ≥ 6 Continue all current tolerated oral diabetic medications except DPP4-inhibitors (e.g. Januvia® (sitagliptin)). Consider reducing sulfonylurea to 50% current dose to reduce the risk of hypoglycemia unless baseline glucose is significantly elevated at initiation of Byetta®.
Use 5 or 8 mm ultrafine pen needles with Byetta®. Store Byetta® in refrigerator until opened. Once opened, may be stored at room temperature (< 77°F). Discard 30 days after first use. Many patients develop nausea. If severe nausea, stop Byetta®. If mild nausea, may continue use as nausea diminishes over time. Avoid if dehydration from nausea and vomiting. Possible increased risk of pancreatitis. If severe abdominal pain or severe nausea and vomiting, stop Byetta® (exenatide) and check lipase/amylase. Evaluate
glucose pattern
after 1 month
Increase Byetta® (exenatide) to 10 mcg BID SQ
* If well tolerated CrCl > 50 ml/min: No adjustment necessary. CrCl 30–50 ml/min: Use caution when initiating or escalating doses. CrCl < 30 ml/min: Not recommended. Evaluate glucose
Consider switch
Byetta® (exentaide)
to insulin
FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to ensure that the benefits of VICTOZA (liraglutide) outweigh the potential risk of medullary thyroid carcinoma and the risk of acute pancreatitis. Selection of Patients:
HbA1c > 7% and
Not on insulin or Byetta (exenatide) Taking at least 1 oral diabetic medication (e.g. metformin) – not recommended 1st line No history or risk of pancreatitis No personal or family hx of medullary thyroid carcinoma or MEN2* Start Victoza® (liraglutide) 0.6 mg SQ once daily for 1 week (starting dose – not effective for glycemic control)
Administer once daily at any time of the day, independently of meals. SQ injection into abdomen, thigh or upper arm – injection site and timing may be changed independent of dose adjustment. Continue all current tolerated oral diabetic medications except DPP4-inhibitors (e.g. Januvia® (sitagliptin)). Reduce sulfonylurea to 50% current dose to reduce the risk of hypoglycemia unless baseline glucose is significantly elevated at initiation of Caution in renal and hepatic impairment; no dose adjustment of liraglutide is recommended. Possible increased risk of pancreatitis. If severe abdominal pain or severe nausea and vomiting, stop liraglutide and check lipase/amylase. Use 5 or 8 mm ultrafine pen needles with liraglutide; discard needle after each injection. Store liraglutide in the refrigerator until opened. After first use, may be stored at room temperature (59ﾺF to 86ﾺF) or in the refrigerator. Discard 30 days after first use. Nausea is common when starting liraglutide. If severe nausea, stop liraglutide. If mild nausea, continue use as nausea diminishes over time ( 4 weeks). ↑ liraglutide to 1.2 mg SQ once daily after 1 week*
* If tolerated; ↑ dose 1.8 mg if needed to achieve glycemic goals * Caution with use in renal/hepatic impairment Evaluate glucose
Increase liraglutide to
1.8 mg SQ once daily*
*if well tolerated Consider switching to insulin
For all Medicines RN / MD should check medication specific contraindications before initiating.
Diabetes Medicines - Titration Table
Class Generic / Brand Name
Initial Dose
Titration Schedule
RN Monitoring Considerations
Metformin 500mg (Glucophage) Renal, CBC 500 mg once daily or Increase by 500 mg weekly to Take with food to decrease GI upset (. breakfast Max dose: 1000 mg bid or 2000 and dinner). This intolerance may improve over Increase by 850 mg every other Recent studies suggest vitamin B12 and/or folic acid deficiency with metformin use; Max dose: 2550 mg daily (3 supplementation may be required. Patient may experience a metallic taste. Metformin SR (Glucophage XR) renal Increase by 500 mg weekly to Start with 500 mg tablets, be alert of the number maximum of 2000 mg daily of tablets patient taking daily and change to 1,000 mg tablets as needed No hypoglycemia, prevents weight gain Max PG effect at 3-4 weeks Increase by 500 mg weekly Max dose: 2500 mg qPM Renal dysfunction (SCr r >1.5 males or >1.4 Increase by 500 mg weekly; females); or abnormal ClCr from any cause Acute or chronic metabolic acidosis Max dose: 2000 mg qPM *Used after GI intolerance to Hold 48 hours before and after surgery or IV contrast radiologic studies; institute only after General y, clinically significant responses are not seen at doses renal function has returned to normal BIGUANIDES
< 1500 mg daily; however a lower recommended starting Black Box Warning:
dose and gradual dose is Lactic Acidosis is rare but serious. The risk of recommended to minimize GI accumulation increases with the degree of renal impairment. Suspect if acidosis without ketoacidosis. If GI side effects occur as dose is Caution / Not recommended:
advanced, decrease to previous
Cautious use in patients  80 years of age lower dose and try to advance at unless normal renal function established Alcoholism, hepatic impairment Use with caution in patients with congestive heart failure requiring pharmacologic management, particularly in patients with unstable or acute heart failure; seek MD guidance Glyburide Regular tabs 2.5 – 5 mg/day Increase by increments no Take 30 minutes prior to meals at same time (Micronase, Diabeta) greater than 2.5 mg weekly each day; give XL tablets with meal (i.e. based on patients FPG *Regular glyburide tablets are response. If dose >10mg/day, Monitor for hypoglycemia (particularly in elderly not interchangeable with consider BID dosing. and renal impairment) and weight gain micronized tablets Max dose: 20 mg/day Glipizide may be preferred in older patient with mildly compromised renal function For elderly or patients with mild Weight gain ( 2kg) common following initiation of to moderate renal dysfunction, initial dose and dose increases Max PG at 5-7 days should be 50% of those above. ▲ Primary drug of choice Glipizide (Glucotrol)▲ Increase by 2.5 – 5 mg weekly until FPG goal or maximum of 40 DKA, Hypersensitivity (rare) mg (total daily dose) or 15 mg (single dose). Doses greater than 15mg should be divided bid. Renal or hepatic dysfunction, escalate to MD as needed For elderly or patients with mild Hypoglycemia: caution with decreased calorie to moderate renal dysfunction, intake, prolonged exercise, alcohol, or if used initial dose and dose increases with other glucose-lowering drugs (e.g. insulin) should be 50% of those above. Do not use concurrently with non-SFU Increase by 2.5 – 5 mg weekly secreatgogues (repaglinide/nateglinide) due to breakfast or the first until FPG goal or maximum of Sulfonamide allergy: potential for cross-reaction G6PD deficiency: refer to MD For elderly or patients with mild Glipizide not recommended with ClCr < 10 ml/min) to moderate renal dysfunction Glyburide not recommended with ClCr< 50mL/min initial dose and dose increments or renal failure should be 50% of those above. Glimepiride (Amaryl) Once 2 mg reached, increase by once daily, with 2 mg every 1-2 weeks until FPG breakfast or the first Max Dose: 8 mg once daily ▲ Primary drug of choice Pioglitazone (Actos)▲ ALT at baseline, 15 – 30 mg daily Increase by 15 mg every 4 May take with or without food and periodically (dose at QHS may weeks until maximum of 45 mg Favorable lipid effects, no hypoglycemia daily if FPG not < 130mg/dl Weight gain: dose-related Fluid retention: may cause significant peripheral edema More prevalent when utilized with Insulin. Adding spironolactone my minimize this. Max effect in 6 – 12 weeks. EF if available or clinical Black Box Warning:
TZDs can cause or exacerbate CHF in some
patients. Not recommended for use with HF sx.
After initiation and dose increases monitor
patients for S/Sx of heart failure (incl. dyspnea,
edema, and excessive, rapid weight gain)
Heart Failure Class III or IV (initiation of treatment), ALT>2.5x ULN complains of nausea, Caution:
May increase risk of fractures of long bones, especially in women Fluid retention may lead or exacerbate heart failure or macular edema (If so, drug should be stopped). Elevated AST or ALT Potential for drug interactions (e.g. bcp) May decrease Hgb/Hct – cautious use in patients with concurrent anemia Fluid retention may lead to or exacerbate heart failure or macular edema; stop drug Glyburide/Metformin Combination products are When patients are stable on these classes of (Glucovance) ▲ (generic) difficult to utilize for dose titration medications there may be a potential for cost savings as they do not allow for flexibility (especially in regards to co-pays) and improved Glipizide/Metformin of increasing individual agents. adherence with combination agents. Assess and (Metaglip)▲(generic) change patients as needed Utilize combination products for patients on stable dose of Monitoring and Contraindication information for multiple medications. individual products should be reviewed. (Actosplus Met XR) Repaglinide/Metformin Sitagliptlin/Metformin COMBINATION AGENTS
▲ Primary drug of choice 120 mg TID prior to Max Dose: 360 mg/day Take 15-30 minutes prior to meals; skip dose if Nateglinide (Starlix) *If close to goal, may No dose adj. for renal or hepatic disease start at 60mg tid Do not use with oral sulfonylureas – similar effect 0.5 mg tid if A1C< 8% Can double pre-prandial dose Potential for drug interactions Repaglinide (Prandin) every week until FPG goals reached or maximum of 4 mg Lower risk of hypoglycemia than SFUs previously treated or QID Max Dose: 16 mg/day DKA, hypersensitivity reactions (rare) Renal or hepatic impairment May cause hypoglycemia Acarbose (Precose) 25 mg tid with first bite Titrate by 25 mg per dose Should be given with first bite of each meal; skip of each main meal every 4-8 weeks intervals until dose if with missed meal 1 hour post-prandial at goal or Start with a low dose and increase slowly to maximum of 100 mg tid (if > minimize GI intolerance. 60kg) or 50 mg TID if < 60kg) GI side effects; flatulence, diarrhea, and abd discomfort, general y diminish over time in the first year; Oral dextrose should be used in the treatment of and periodically 25 mg tid with first bite mild to moderate hypoglycemia of each main meal Titrate by 25 mg per dose Miglitol (Glyset) every 4-8 weeks intervals until 1 hour post-prandial at goal or Bowel disease, DKA, cirrhosis (Acarbose only), GI INHIBITIORS
maximum of 100 mg tid Max dose: 100 mg tid Warning:
Use not recommended with significant impairment (SCr > 2 mg/dL) Dose-related, transient increase in AST/ALT Sitagliptin (Januvia) No titration required May be taken with or without food Cases of acute pancreatitis reported with use; Mild to moderate renal discontinue if suspected (Sitagliptin only) dysfunction (ClCl >30ml/min and  No hypoglycemia or weight gain <50ml/min): decrease dose to PG effect within 1-2 weeks of initiation Common AEs: Headache, URI and/or UTI (persistent, severe abd pain, Severe renal dysfunction or ESRD: decrease dose to 25 Hypersensitivity e.g. anaphylaxis, angioedema (Sitagliptin only) Warnings
Saxagliptin (Onglyza) 2.5 – 5 mg once daily ClCl< 50 ml/min: 2.5 mg/day Renal function impairment: adjust dose DPP-4 INHIBITOR
Drug interactions e.g. clarithromycin, administered with itraconazole, nefazodone, protease inhibitors (Saxagliptin only) Hepatic impairment (Sitagliptin only) Use caution in patients with a hx of pancreatitis (Sitagliptin only) ▲ Primary drug of choice Do not use Byetta and DPP4-inhibitors together
Exenatide (Byetta) Increase to 10 mcg bid after 1 Injectable given twice a day at anytime within 1
month if patient not at goal and hour before morning and evening meal or before
tolerating GI effects the 2 main meals of the day, approximately 6 hours apart - Not to be taken after meals May result in a reduction in appetite, food intake, and/or body weight Discard pen after 30 days Main side effects nausea/vomiting(improve over time) and weight loss For oral medications that have a narrow therapeutic window or require rapid absorption, (e.g. contraceptives, antibiotics) patients should be advised to take those drugs at least 1h before BYETTA injection. Contraindications:
Hypersensitivity; Not recommended in patients with
ESRD or ClCr <30 ml/min, gastroparesis, GI disease,
Warnings:
Acute pancreatitis has occurred after initiation of exenatide and after dose increases - observe pts INCRETIN MIMETIC
carefully for S/Sx of pancreatitis (including persistent, severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting) with renal transplantation and with exenatide initiation or dose increases in patients with moderate renal impairment (Clcr 30- Use with caution with sulfonylurea; may increase risk of hypoglycemia – consider reducing dose of SFU May increase INR, increase monitoring when initiating in patients on Coumadin (warfarin) Do not use Byetta and DPP4 inhibitors together
▲ Primary drug of choice 0.6 mg SC once daily After 1 week, increase the dose No dose adjustments in renal/hepatic impairment to 1.2 mg SC once daily. Administer once daily at any time of day, independently of meals If the 1.2 mg dose does not Pen should be discarded 30 days after initial use result in acceptable glycemic Use assoc. with weight loss control, the dose can be Common AEs: headache, nausea, and diarrhea. increased to 1.8 mg SC once Nausea is most common when first starting radiating to the liraglutide, but decreases over time. back that may or may not be Max dose: 1.8 mg/day SC Black Box Warning
Dose- and duration- dependent thyroid C-cell tumors have developed in animal studies with liraglutide therapy; relevance in humans unknown. Contraindications
History of or family history of medullary thyroid
carcinoma (MTC); patients with multiple endocrine
neoplasia syndrome type 2 (MEN2)
Warnings:
GLP-1 RECEPTOR AGONIST
Cautious use with GI disease (gastroparesis) Acute and chronic pancreatitis:if suspected, discontinue use Use with caution with sulfonylurea; may increase risk of hypoglycemia – consider reducing dose of SFU Pramlintide (Symlin) Increase to 120 mcg if patient Reduce pre-meal insulin dose by 50%; after the immediately prior to is tolerating without maintenance dose of pramlintide is reached, nausea/vomiting after 3-7 days. adjust insulin to achieve optimal glycemic control No dose adjustments in renal/hepatic impairment If nausea occurs at 120 mcg, Administer subcutaneously immediately prior to decrease dose to 60 mcg TID. each major meal (at least 250 kcal or containing at least 30 g of carbohydrate). Max Dose: 120 mcg/dose SC Do not mix pramlintide with any type of insulin * Reduce pre-meal insulin dose Contraindications: Allergy, gastroparesis or
by 50%; after the maintenance hypoglycemia unawareness. dose of pramlintide is reached, adjust insulin to achieve Warnings:
optimal glycemic control Potential for hypoglycemia AMYLIN ANALOG
Nausea / vomiting primary side effect, tolerance develops over time. Pramlintide may alter absorption of oral medicines; administer the agent at least 1 hour prior to or 2 hours after pramlintide injection OnlineTM , Pediatric Lexi-Drugs OnlineTM , Hudson, Ohio: Lexi-Comp, Inc.; Accessed July 31, 2010. 2. Facts & Comparisons. Facts & Comparisons Web site. /. Accessed July 31,2010. 3. Clinical PharmacolJuly 31, 2010. ▲ Primary drug of choice

Source: http://www.suttermedicalfoundation.org/spa/about/forourphysicians/guideline_typeii_diabetes.pdf