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Home , Acarbose, Alogliptin, Canagliflozin, Chlorpropamide, Diabetes management, Glimepiride

DIABETES DOSING GUIDE THE FOLLOWING TABLE DETAILS DOSING RECOMMENDATIONS FOR TREATMENT AGENTS Dosing Adjust- A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 ments1,2 Notes 3-5 Potential 2

Increase in 500mg 500mg BID or increments or Up to 2550mg Glucophage® 850mg Daily 850mg every 2 daily weeks

Metformin 1000 to 2000 mg Up to 2000mg Glucophage XR® 500mg daily Low risk of Extended Release daily daily Contraindicated Metformin 1000 to 2500mg Up to 2500mg Fortamet® 500-1000mg daily for patients with Gastrointestinal Extended Release daily daily renal insufficiency side effects Metformin 500 to 2000mg Up to 2000mg Glumetza® 500mg daily First line treatment Extended Release daily daily

Increase in 500mg Metformin 500mg BID or increments or Up to 2550mg Riomet® solution 850mg Daily 850mg every 2 daily weeks 1-1.5% 100 to 250 mg Up to 1000mg Tolinase® daily with the first Notable daily meal of the day hypoglycemia risk lose effectiveness No dosing due to their adjustments mechanism required. Initial of action.

hepatic and Effectiveness is Sulfonylureas renal impairment lost as Orinase® 1 to 2 g daily Up to 3g daily dosing should be damage conservative. progresses in some diabetics 8

Loses effectiveness and causes weight gain Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2 Long half life, can be as long as 72 hours Should be avoided Notable * Diabinese® 250mg daily 100 to 500mg daily Up to 750mg daily in those with CrCl hypoglycemia risk <50mg/dl Loses effectiveness and causes weight gain No dosing adjustments required Titrate in 2.5 to Glucotrol® 5mg daily Up to 40mg daily 5mg increments Doses over 10mg/day shown no increased effectiveness No dosing adjustments Higher risk of required hypoglycemia Sulfonylureas Sulfonylureas Dosing should considered 1-1.5% (continued) be titrated conservatively second line by the Glipizide Glucotrol XL® 5mg daily 5 to 10mg daily Up to 20mg daily in those with ADA and add on hepatic or renal therapy by AACE impairments May cause Doses over weight gain 10mg/day shown Glyburide and no increased chlorpropamide effectiveness are considered No dosing high risk increase in 1 to 2 Amaryl® 1 to 2 mg daily Up to 8mg daily adjustments medications due mg increments required to increased risk of hypoglycemia Doses over 10mg/day shown Up to 5mg daily no increased initially effectiveness3 Glyburide* Diabeta® 2.5 to 5mg daily 1.25 to 20mg daily Up to 20mg daily Should not be as maintenance used in patients with CrCl <50ml/min

- 2 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

Up to 3mg Glynase 0.75 to 12mg daily daily initially Glyburide* 1.5 to 3mg daily Doses over (Micronized)® or in split doses Up to 12mg daily 10mg/day shown as maintenance no increased effectiveness3 Higher risk of Should not be hypoglycemia Up to 5mg daily used in patients Sulfonylureas initially with CrCl considered Glyburide* Micronase® 2.5 to 5mg daily 1.25 to 20mg daily <50ml/min Up to 20mg daily second line by the as maintenance ADA and add on therapy by AACE Sulfonylureas May cause 1-1.5% (continued) weight gain Glyburide 1.25/ No dosing Glyburide / 2.5mg/500mg to Up to 20mg/ Glyburide and Glucovance® Metformin adjustments Metformin* 5mg/500mg BID 2000mg daily chlorpropamide 250mg BID required are considered Doses over high risk 10mg/day shown medications due no increased to increased risk of effectiveness3 hypoglycemia Glipizide 2.5mg/ Increase in Glipizide / Up to 20mg/ Contraindicated MetaglipTM Metformin increments of Metformin 2000mg daily for patients with 500mg BID 5mg/500mg renal insufficiency

CrCl 20-40mL/min: 0.5mg BID to QID May double the Do not use with Prandin® Up to 16mg daily Start at 0.5 mg and prior to each meal dose weekly sulfonylureas titrate carefully Risk of hypoglycemia 0.5-1% Prandin is more effective than No dose 120mg TID prior Starlix at Starlix® adjustments to a meal lowering A1C required

- 3 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

Caution use in patients, black box warning.

Increase 15mg Increased risk of Actos® 15 or 30 mg daily Up to 45mg daily increments peripheral edema and weight gain

Avandia- only available through Avandia- Rosiglitazone Medicines Patients with program If there is elevated insufficient These agents 4mg daily or transaminases Rosiglitazone Avandia® plasma Up to 8mg daily can be used in 2 doses or hepatic response, increase impairment with metformin to 8mg daily should avoid as second line this or as part of Thiazolidine- a multi-drug 0.5-1.4% diones Patients with CHF regimen class I or II should use no more than Caution use in 15mg daily heart failure Patients with CHF patients, black box class III or IV are warning. contraindicated Increased risk of peripheral edema and weight gain Pioglitazone 15/ Pioglitazone/ Actoplus Titrate based on Up to 45/ Contraindicated Metformin500 BID Metformin metformin® tolerability 2550mg daily for patients with or 15/850 daily renal insufficiency

These agents can be used with metformin as second line or as part of a multi-drug regimen

- 4 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

Pioglitazone Pioglitazone/ Actoplus 15/ Metformin Titrate based Up to 45/ Metformin XR Metformin XR® 1000mg or on tolerability 2000mg daily 30/1000 daily Caution use in heart failure patients, black box warning

Previously Increased risk of received peripheral edema rosiglitazone and weight gain 4mg daily: Rosiglitazone/ 2/500mg BID Contraindicated Avandamet® Metformin Patients with for patients with Previously elevated renal insufficiency received transaminases rosiglitazone or hepatic 8mg daily: impairment 4/500mg daily should avoid Thiazolidine- this drug diones 0.5-1.4% Patients with CHF (continued) Rosiglitazone class I or II should 4mg/ Increase by no use no more than Rosiglitazone/ Up to 8mg/ Avandaryl® glimiperide1mg more than 2mg 15mg daily Glimiperide 4mg daily Caution use in daily with increments Patients with CHF heart failure first meal class III or IV are patients, black box contraindicated warning Increased risk of Pioglitazone peripheral edema 30mg/ Glimiperide and weight gain 2mg or 30mg/ Avandia- 4mg daily Rosiglitazone Titrate gradually Pioglitazone/ Patients previously Up to 45mg/ only available Duetact® based on Glimiperide on glimepiride 8mg daily through Avandia- monotherapy tolerability Rosiglitazone or pioglitazone Medicines monotherapy have program the same initial dose

- 5 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

May be increased Up to 50mg TID for 25mg TID with to 50-100mg TID those <60kg No significant Acarbose Precose® the first bite of at four to eight weight changes each meal Up to 100mg TID week intervals for those >61kg ADA considers this third line

May cause hypoglycemia, risk is higher when used with Alpha- Dose titration or sulfonylureas Glucosidase will limit 0.5-0.8% inhibitors gastrointestinal Useful in side effects decreasing post-prandial glucose levels

Contraindicated in patients with inflammatory bowel disease, colonic ulceration, partial or complete 25mg TID 50mg TID up to 100mg intestinal Glyset® with meals with meals TID daily obstruction

- 6 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

CrCl 30ml/min and Januvia® 100mg daily : 25mg

Risk of nasopharyngitis, upper respiratory tract CrCl <50ml/min Saxagliptin Onglyza® 2.5 to 5mg daily or strong CYP3a4 Risk of inhibitor: 2.5mg hypoglycemia

Weight neutral

Rare cases of DPP4-Inhibitors 0.5-1% ADA considers second line after metformin

No renal dosing Should not be Tradjenta® 5mg daily necessary used with DM type 1 or for the treatment of

CrCl 30—59 ml/ min: 12.5 mg daily Alogliptan Nesina® 25mg daily CrCl < 30 ml/min: 6.25 mg daily

- 7 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

Previously on Metformin: Sitagliptin 50mg plus current dose of Metformin BID

Previuosly on 850mg CrCl 30ml/min and Metformin / Metformin BID: Janumet® dialysis: 25mg of Sitagliptin Sitagliptin 50mg Sitagliptin plus 1000mg Metformin BID Risk of nasopharyngitis, Previuosly on upper respiratory Sitagliptin: tract infection Sitagliptin 50mg plus 500mg Risk of Metformin BID hypoglycemia Weight neutral

Rare cases of DPP4-Inhibitors Previously on pancreatitis 0.5-1% (continued) Metformin: Sitagliptin 100mg ADA considers plus current dose second line after of Metformin daily CrCl 30ml/min and metformin Metformin / Janumet xr® dialysis: 25mg of Sitagliptin Previuosly on Should not be Sitagliptin 850mg Metformin used with DM BID: 2 tablets of type 1 or for Sitagliptin 50mg the treatment plus 1000mg of diabetic Metformin daily ketoacidosis

Linagliptin 2.5mg/ No renal dosing Metformin 500mg necessary BID with meals Up to 2.5mg/ Metformin / Metformin should Jentadueto® Currently using Metformin Linagliptin be avoided for Metformin: 2.5mg/ 1000mg BID those with renal current dose for insufficiency Metformin BID

- 8 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

CrCl 30ml/min to CrCl 50ml/ min should not be higher than Sitagliptin 100mg/ sitagliptin 50mg/ Sitagliptin/ JuvisyncTM 40mg simvastatin 40mg Simvastatin QHS CrCl <30ml/min: avoid using

Liver disease: Risk of Contraindicated nasopharyngitis, upper respiratory tract infection

Risk of Has not been hypoglycemia studied in Weight neutral combination with insulin Rare cases of DPP4-Inhibitors pancreatitis 0.5-1% (continued) Dose should be individualized ADA considers Should be based on current second line after 5mg/ Up to saxagliptin Saxagliptin / adjusted based regimen and metformin Kombiglyze xr® Metformin 500mg 5mg/ metformin Metformin on prior or current tolerability daily 2000mg daily therapy Should not be Concomitant used with DM use with strong type 1 or for CYP3A4 inhibitors the treatment should use of diabetic saxagliptin ketoacidosis 2.5mg/metformin 1000mg daily

Alogliptin 25mg Metformin should Metformin/ / Metformin be avoided for Kazano® 2000mg per day those with renal with meals insufficiency

- 9 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2

Risk of genital Should be avoided FarxigaTM 5mg daily Up to 10mg daily in those with CrCl <60mg/dl Increased risk of urinary tract infections, vulvovaginal pruritus, and Sodium-Glucose increased Co-Transporter 2 Should not exceed urination 0.7-1% (SGLT2) Inhibitors 100mg in patients Up to 300mg daily with CrCl 45ml/ May cause if GFR is >60ml/ Invokana® 100mg daily min to 60ml/min min and additional Risk of efficacy is required Should be avoided in those with CrCl hypoglycemia <45ml/min when used in combination with other agents

No hypoglycemia 5mcg 10mcg subcutaneously subcutaneously Weight loss BID within 60 BID within Byetta® minutes before 60minutes before Risk of pancreatitis the morning and the morning and No dose Injection evening meal evening meal adjustment -Like medications requirements, Peptide-1 (GLP1) 0.4-0.9% caution should Can be used in be used when combination with adjusting dosage other medications as add on therapy

Should not be used with prandial 2mg insulin Exenatide Bydureon® subcutaneously extended release once every 7 days

- 10 - Dosing A1C Lowering Class Generic Name Brand Names Initial Dose1 Maintenance Dose1 Max Dose1 Adjustments1,2 Notes Potential 2 No hypoglycemia

Weight loss

Risk of pancreatitis

No dose Injection Glucagon-Like 0.6mg adjustment 1.2 medications Peptide-1 (GLP1) subcutaneously requirements, Victoza® subcutaneously Up to 1.8mg daily 0.4-0.9% Agonists daily for 1 week to caution should Can be used in daily (continued) reduce GI effects be used when combination with adjusting dosage other medications as add on therapy

Should not be used with prandial insulin

Hypoglycemia risk requires reduction in insulin No specific renal dosage Injection 60mcg 120mcg adjustments medication Analogs Symlin® subcutaneously subcutaneously 0.5-1% Risk of prior to meals if tolerated Should not be coadministered Weight loss with insulin ADA considers this medication as third line

Suggested Medications for Patients with Diabetes 6,7 - Patients with diabetes and high risk cardiovascular risk should be considered for low dose aspirin. ACEI / ARB 6,7 - Patients with diabetes should be considered for ACEI or ARB if they have hypertension and/or for general prevention to macro albuminuria from micro albuminuria.

References 1. DRUGDEX System (Micromedix 2.0) Greenwood Village, CO: Truven Health Analytics; c1974-2014. http://www.micromedexsolutions.com/home/dispatch. Accessed May 2014. 2. for . PHARMACIST’S LETTER / PRESCRIBER’S LETTER. June 2012.Therapeutic Research Center. www.pharmacistsletter.com 3. Diabetes Mellitus (DM): Treatment. http://www.merckmanuals.com/professional/. 2010-2013 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A 4. AACE Comprehensive Algorithm, Endocr Pract. 2013; 19(No2). Copyright 2013. 5. Fowler, Michael J. “Diabetes Treatment, Part 2: Oral agents for glycemic management.” Clinical diabetes 25.4 (2007): 131-134. 6. Does My Patient with Diabetes Need an Aspirin, Statin, ACE Inhibitor, or ARB.PHARMACIST’S LETTER / PRESCRIBER’S LETTER. Therapeutic Research Center. www.pharmacistsletter.com 7. Nathan, David M., et al. “Medical management of 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 32.1 (2009): 193-203. 8. Christopher D. Saudek, Simeon Margolis. Diabetes 2007. Johns Hopkins White Papers. Johns Hopkins Health, 2007. *: These medications are considered high risk Highmark is a registered mark of Highmark Inc. 6/14 CS 201769 - 11 -