for Health Care Providers

Management of Diabetes Mellitus

Intervention	Dosage	Comments
Abbreviations: N = NPH; NPA = neutral protamine aspart; NPH = neutral protamine Hagedorn; NPL = neutral protamine lispro; R = regular Note: Glargine cannot be diluted or mixed with other insulins.
Behavior modification	Reinforce at every visit	Institute for all patients Weight loss for overweight or obese patients, avoiding overweight for others Limit alcohol use (no more than 2 standard drinks/day for men, 1 standard drink/day for women; see Alcohol Misuse) Balanced American Diabetes Association diet Daily exercise; at least 2.5 hours per week For further resources, see MOVE! (the VA NCP weight management program), American Diabetes Association, and the VA Obesity Clinical Practice Guidelines
Diet	50-60% carbohydrates (preferably complex) 10-20% protein <30% fats (<7% saturated fats) <300 mg/day of cholesterol Limit trans fats	Institute for all patients Refer for dietary counseling and diabetes education as needed For further resources, see MOVE! (the VA NCP weight management program), American Diabetes Association, and the VA Obesity Clinical Practice Guidelines
Education	As needed	Refer all patients for diabetes education
Medications
Oral agents
Biguanide: metformin metformin extended release	Immediate release: start with 500 mg BID or 850 mg daily Increase as needed to 850 mg TID or 1,000 mg BID (maximum of 2,550 mg/day divided into 2-3 doses) Extended release: start with 500 mg daily. May increase by 500 mg daily each week to (maximum 2,000 mg/day)	Lowers HbA_1c by about 1.5% Preferred first-line treatment for most patients, especially those with BMI >25 Insulin sensitizer May promote weight loss, which is useful for overweight patients Potential adverse effects: nausea, diarrhea, gas, abdominal pain (take with food to reduce GI effects), lactic acidosis Contraindicated in renal insufficiency (men: Cr level >1.5 mg/dL; women: Cr level >1.4 mg/dL), CHF For patients on NRTIs, especially d4T and ddI, there may be compounded risk of lactic acidosis May improve lipoaccumulation (mixed results in studies) but may worsen lipoatrophy Hold in patients about to receive IV iodinated contrast until 2-3 days after the contrast, and verification that serum Cr is normal (to reduce the risk of contrast nephropathy) Hold after surgical procedures until Cr, and urine output are normal and fluid.
Sulfonylureas: glipizide, glyburide	Glipizide: start with 2.5-5 mg QAM; maximum of 40 mg/day (divided into 2 doses) OR Glipizide XL 5-10 mg QAM Glyburide: start with 1.25-2.5 mg QAM or BID (maximum of 20 mg/day, may be divided into 2 doses) Take glipizide 30 minutes before a meal	Lowers HbA_1c by about 1-2% Increases insulin secretion Hypoglycemia is the most common adverse effect; patients should be counseled to watch for symptoms and to take these agents with food. Shorter-acting sulfonylureas such as glipizide and gliclazide are preferred, especially in older patients, to reduce the risk of prolonged hypoglycemia. Dose cautiously in patients with renal insufficiency: glyburide is 50% renally cleared and has T½ of 10 hours; glipizide is 80% renally cleared and has T½ of 2-5 hours; start at low dosage, increase slowly; decrease dosage or discontinue if renal function worsens Glipizide does not have an active metabolite; use preferentially in chronic renal failure Potential adverse effects: hypoglycemia, weight gain (approx. 4-5 lb in the first year), rash, elevation of serum transaminase levels
Thiazolidinedione: pioglitazone	Start with 15 mg QD Increase as needed, up to 45 mg QD	Lowers HbA1c AIC by about 0.5-1.4% FDA is reviewing complications. Currently not on VHA formulary; for combination therapy in selected patients Not recommended for monotherapy unless: Patient is intolerant of or has contraindications to both sulfonylureas and metformin; and Target HbA1c is likely to be attained Absolute contraindications: Type 1 diabetes or prediabetes CHF: NYHA Class III or IV Active liver disease or ALT >2.5 times upper limit of normal Jaundice or CHF on another thiazolidinedione Pioglitazone is the preferred thiazolidinedione; rosiglitazone is no longer recommended by the ADA owing to studies showing an increased risk of MI and CV death Monitor fluid/volume status Potential adverse effects: weight gain (˜10 lbs in first year of treatment), edema, CHF; reduction in bone mineral density and increased risk of fractures; possible increased risk of MI; caution in patients with high risk of CV events (particularly with rosiglitazone). May improve nonalcoholic hepatic steatosis May improve lipoatrophy (mixed results in studies)
DPP-IV inhibitors: sitagliptin, saxagliptin	Sitagliptin 100 mg QD Reduce to 50 mg QD for patients with CrCl 30-50 mL/min Reduce to 25 mg QD for patients with CrCl <30 mL/min and ESRD Saxagliptin 2.5-5 mg QD Reduce to 2.5 mg for CrCl <50 mL/min; give dose after dialysis if on HD	Nonformulary in VHA; see PBM Criteria for Use Primarily used as an add-on drug, but also may be used in patients with contraindications to metformin, sulfonylureas, or thiazolidinediones Potential serious adverse effects include anaphylaxis, angioedema, and Stevens-Johnson syndrome
Glucagon-like peptide 1 agonists: exenatide, liraglutide	Exenatide 5 µg SQ BID Liraglutide, start at 0.6 mg SQ QD forx 1 week, then 1.2 mg QD, maximum 1.8 mg QD	Use restricted to diabetes specialists in VHA; see PBM Criteria for Use Add-on drug for patients not controlled on 1-2 other oral agents. Induces weight loss. Increased risk of pancreatitis.
Meglitinides: repaglinide (preferred), nateglinide	Repaglinide 0.5-4 mg PO before meals; start at 0.5 mg; titrate with caution in renal insufficiency Nateglinide 60-120 mg PO TID 1-30 minutes before meals	Nonformulary in VHA; see PBM Criteria for Use Short-acting agents that act similarly to sulfonylureas, but are somewhat less effective at lowering HbA_1c Generally added to metformin monotherapy; no added benefit if used with other insulin secretagogues such as sulfonylureas Repaglinide can be considered first-line monotherapy in patients with contraindications to metformin and sulfonylureas. Caution in patients with hepatic and/or renal insufficiency Expensive
Alpha-glucosidase inhibitors: acarbose, miglitol	Acarbose or Miglitol: 25-100 mg PO TID at the start of each meal; start at 25 mg TID	Miglitol is nonformulary in VHA Lowers HbA_1c AIC by about 0.5-0.8% Add-on drug for patients not controlled on 1-2 other oral agents Main side effects are flatulence and diarrhea, which can significantly limit tolerance (and thus are not recommended by the ADA as second-line agents) Acarbose contraindicated in patients with cirrhosis
Insulin	See below for formulations and dosing; potential adverse effects: weight gain, hypoglycemia
	Onset	Peak (hours)	Duration (hours)
Rapid acting
Insulin lispro	10-15 min	1-2	3-5
Insulin aspart	10-15 min	1-2	3-5
Short-acting: regular	0.5-1 h	2-4	4-8
Intermediate acting
NPH	1-3 h	4-10	10-18
Lente	2-4 h	4-12	12-20
Long acting
Insulin detemir	2-3 h	None	Up to 24
Insulin glargine	2-3 h	None	24+
Premixed insulins
70/30 (70% N + 30% R)	0.5-1 h	2-10	10-18
75% NPL + 25% lispro	10-15 min	1-3	10-16
70% NPA + 30% aspart	10-15 min	1-3	10-16

From Diabetes
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009