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Management of Diabetes Mellitus

for Health Care Providers

Management of Diabetes Mellitus

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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 modificationReinforce at every visit
  • 50-60% carbohydrates (preferably complex)
  • 10-20% protein
  • <30% fats (<7% saturated fats)
  • <300 mg/day of cholesterol
  • Limit trans fats
  • As needed
  • Refer all patients for diabetes education
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 HbA1c 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)


  • 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 HbA1c 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 HbA1c
  • 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 HbA1c 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
InsulinSee below for formulations and dosing; potential adverse effects: weight gain, hypoglycemia
OnsetPeak (hours)Duration (hours)
Rapid acting
Insulin lispro10-15 min1-23-5
Insulin aspart10-15 min1-23-5
Short-acting: regular0.5-1 h2-44-8
Intermediate acting
NPH1-3 h4-1010-18
Lente2-4 h4-1212-20
Long acting
Insulin detemir2-3 hNoneUp to 24
Insulin glargine2-3 hNone24+
Premixed insulins
70/30 (70% N + 30% R)0.5-1 h2-1010-18
75% NPL + 25% lispro10-15 min1-310-16
70% NPA + 30% aspart10-15 min1-310-16

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