Antidiabetic Medication
See also:

Note--The discussion below is focused primarily on Type 2 Diabetes Mellitus, though there is information applicable to type 1 also.

I. Initial workup

  1. History
    1. Confirm dx--see also "Definitions" section regarding diagnostic criteria
    2. Review previous & current tx
    3. Assess past & recent glycemic control--glucose, HbA1c
    4. Determine presence/stage of chronic complications--renal, ophthalmologic, neurologic (gastroparesis, erectile dysfunction in male, bladder), cardiovascular including PVD & CVA
    5. Review Sx
    6. Assess other cardiac risk factors
    7. Exercise habits
    8. Review h/o acute complications, including hypoglycemia, DKA, hyperosmolar hyperglycemic nonketotic sd, infection (skin, foot, GU, etc.)
    9. Check if on any meds that may affect blood sugar
    10. OB hx/contraception in female
  1. Physical exam
    1. Ht, Wt, BMI, BP
    2. Skin (including insulin injection sites)
    3. Eyes including fundi
    4. Oral cavity & dentition
    5. Thyroid
    6. Heart
    7. Abdomen
    8. Pulses
    9. Hands & feet
    10. Neurologic exam
  1. Assess glycemic control
  1. Fasting plasma glucose
  2. HbA1c--note this may be altered in pts with Hemoglobinopathies
  1. Serum Creatinine
  2. Urinalysis with micro; culture if abnormal or symptomatic
  3. ECG
  4. Initiate routine diabetic screening as below (section IX.) with fasting lipids, microalbuminuria screen, retinopathy screen, etc.
  5. Workup for secondary causes, as clinically indicated:
    1. Hemochromatosis
    2. Hypothyroidism
    3. Pancreatic parenchymal disease
    4. Acromegaly
    5. Pheochromocytoma
    6. Cushing's disease

II. Lifestyle changes

  1. Exercise-consider noninvasive cardiac testing (e.g. Exercise Treadmill Test) before starting, esp. if other risk factors for CAD
  2. Nutrition education and dietary modification-See under Glycemic Control for more information
  3. Weight loss if obese (note that bariatric surgery may be helpful in improving glycemic control in diabetics; click link for details)
  4. Smoking cessation if a smoker

III. Glycemic Control (click on link for details)

IV. Periodic follow-up care including screening in pts with type 2 DM

  1. ADA recommends at least Q3mo visits "until achievement of treatment goals"
  2. Assessment of Glycemic Control with HbA1c at least Q6mos; Q3mos if changing tx or not meeting tx goals
  3. Screening for Retinopathy: comprehensive, dilated fundoscopic exam soon after diagnosis and Q1y thereafter
    1. Stereoscopic fundus photography is an alternative modality but is not as widely available
    2. During pregnancy, women with DM should get comprehensive eye exam in 1st trimester and "close followup throughout pregnancy" per ADA 1998--n.b. this does not apply to women who develop gestational DM during pregnancy!
  4. Screening for Nephropathy Q1y
    1. Some recommend screening for both microalbuminuria (as below) and renal insufficiency (with serum Cr and GFR estimation)
    2. Albuminuria screening methods:
      1. Spot urine albumin-creatinine ratio (first am void preferred; should be < 30ug/1mg)
      2. 24h urine albumin excretion (gold standard; use to confirm abnormal spot urine albumin-to-creatinine ratio)
      3. Timed (< 24h) urine albumine excretion
      4. Note that ADA says you can start with standard dipstick urinalysis for protein and if positive, go straight to 24h protein excretion; albumin, which is main protein spilled in diabetic nephropathy, doesn't show up on standard urine dipsticks for protein
    3. Avoid screening for microalbuminuria in setting of UTI, marked HTN, severe CHF, heavy exercise, febrile illness, or recent hyperglycemia; all of these can cause transient albuminuria
    4. Confirm microalbuminuria with a repeat study sev. weeks later; 2 out of 3 over 3-6mos with any of the above methods considered diagnostic of microalbuminuria, consider nephrology consult if get conflicting results
    5. Microvascular complications tend to occur together, so nephropathy without retinopathy warrants search for other causes, e.g. NSAID
  5. Screening for Dyslipidemias with fasting lipid panel Q1y
  6. Screening for Diabetic Foot Disease and risk of same per ADA
    1. Annual "comprehensive screening including vascular, neurological, musculskeletal, and skin and soft tissue evaluations"--pulses, inspections for ischemic changes, sensory and motor exam
      1. Per ADA, determination of "protective sensation" is with a 10g (5.07) Semmes-Weinsteini monofilamint--should be able to "consistently feel the touch" of the monofilament.
    2. In high-risk pts (loss of "protective sensation," vascular disease, skin or nail abnormalities, or h/o previous ulcers or amputations), ADA reccs foot exam at each routine DM visit "several times a year" inc.:
      1. Looking for fungal infection, ulcers or skin breakdown
      2. "Assessment of gait and determination of ROM at the ankle and hallux"
      3. Comprehensive preventive foot program (see Foot Disease page).
  7. Other components of periodic DM visit recc'd by ADA:
    1. Review management plan (see below) & tx goals
    2. Assess pt's knowledge & self-management skills
    3. Review glycemic control inc. hypoglycemia
    4. Review tx including nutrition & exercise, and assess adherence
    5. Review sx of DM and of complications
    6. Address cardiac risk factor reduction
    7. Px--Wt, BP, foot & eye exams as above

V. The Diabetes "Patient Management Plan"--a potentially useful tool in patient self-management. Items to cover:

  1. Short & Long-term goals, including goals for glycemic control
  2. Medications
  3. Nutrition recommendations
  4. Exercise recommendations
  5. Other lifestyle recommendations if indicated, including cardiac risk reduction
  6. Contraception plan if at risk for pregnancy
  7. Education re: self-management
    1. Dental hygeine
    2. Signs of acute & chronic complications, especially foot infections
    3. Hypoglycemia management if appropriate
  8. Glucose monitoring instructions
  9. Followup plan
  10. Planned consultations and screening tests
  11. How to contact MD
  12. "Bring this & all meds w/you to all visits"

VI. Control Hypertension, if present (click on link for discussion of pharmacologic management of hypertension in diabetics)

  1. Target BP
    1. JNC VII (JAMA 289:2560, 2003) & ADA say to 130/80, ACP-ASIM recommend 130-135/<80 (Ann. Int. Med. 138:587, 2003)
    2. In a randomized trial of target DBP of 80, 85, or 90; no sig. diffs. in clincial outcomes were seen among the groups overall, BUT among diabetics, 80mm Hg group had sig. lower risk for CV death than 85 or 90 groups and sig. lower risk for major CV events than 90 group ("HOT" study--Lancet 351:1755, 1998)
    3. In a randomized trial in 1,148 pts with type 2 DM and HTN to BP targets of 150/85 vs. 180/105, over mean 8.4y f/u, tighter group had sig. lower risk CVA, diabetes-related mortality (RR 0.68), and various other DM-related endpoints; nonsig. reduction in all-cause mortality (UK Prospective Diabetes Study "UKPDS 38"--BMJ 317:703, 1998)
    4. In a study of the subjects of UKPDS 38 (see above), over median 9.,3y f/u, the incidence of blindness in at least one eye was sig. lower in the tight control group (2.4% vs. 3.1%) as was incidence of significant deterioration of vision (20.5% vs. 32.8%) (UK Prospective Diabetes Study "UKPDS 69; Arch. Ophth. 122:1631, 2004--AFP)
    5. 3,462 pts with type 2 DM randomized to "standard" vs. "tight" BP control; pts with lower BP's found to have lower risk of DM-related complications and DM-related death; there was no BP threshold below which further BP reduction appeared not to offer additional benefit (UK Prospective Diabetes Study "UKPDS 36"; BMJ 321:412, 2000--JW)
    6. In a randomized of 470 pts w/DM & HTN to DBP targets of 75mm Hg or 80-89mm Hg, at 5y f/u, no sig. diffs. in incidence of progression of nephropathy, retinopathy, or neuropathy, BUT all-cause mortality was sig. lower in tighter-control group (5.5% vs. 10.7%) (Appropriate Blood Pressure Control in Diabetes ("ABCD") study (Diab. Care 23(suppl. 2):54, 2000)
    7. In a retrospective study in 6,400 pts > 50yo with diabetes mellitus and coronary artery disease who were participants in the "International Verapamil SR-Trandolapril" ("INVEST") study, all of whom received treatment with either a Ca-blocker or a beta-blocker followed (if necessary) by either or both of (an ACE inhibitor or a diuretic) with target BP of <130/<85, pts who achieved "tight control" (SBP < 130) had similar incidence of primary endpoint (death, MI, or CVA) as pts who achieved SBP 130-139 (12.7% vs. 12.6%), but pts with SBP > 140 had sig. higher incidence of the endpoint (19.8%) (JAMA 304:61, 2010-abst)
    8. In a study in 4,733 pts with type 2 DM randomized to "intensive" BP control (to target SBP < 120mm Hg) vs. "standard" BP control (target SBP < 140mm Hg), over mean 4.7y f/u, there was no sig. diff. in incidence of (MI, CVA, or cardiovascular death) or overall mortality, though incidence of CVA was sig. lower in intensive BP control group (HR 0.59, ARR 0.21%/yr); incidence of serious adverse events attributed to antihypertensive tx was sig. higher in intensive tx group (3.3% vs. 1.3%) ("ACCORD" Trial group; NEJM 362:1575, 2010)

VI. Control Dyslipidemias if present--Click on link for details

VII. If early-stage Diabetic Nephropathy is present:

  1. ACE Inhibitors will slow progression though ADA stops short of mandating their use in normotensive Type 2 diabetics with microalbuminuria ("clearly indicated [if] progression of albuminuria" is detected (1998 Practice Recommendations)
  2. Low-protein diet may slow progression

VIII. Consider fenofibrate to  reduce risk of LE amputations in pts with DM (click on link for details)

IX. Offer contraception if female at risk for pregnancy

  1. Exercise
  2. Weight reduction if obese
  3. Chromium supplementation for Diabetes Mellitus
    1. Chromium has been shown to increase insulin sensitivity & binding
    2. Chromium picolinate 1mg/d was ass'd with sig. greater decrease in HbA1c than placebo in a randomized trial of 180 pts (Diab. 46:1786, 1997--FP News 2/1/01)
  4. Ginseng supplementation for Diabetes Mellitus
    1. 9 pts with type 2 DM and 10 controls randomized to American Ginseng (Panax quinquefolius L) 3g vs. placebo 40min before a 25g oral glucose challenge test; sig. lower glucose levels in the ginseng recipients (Arch. Int. Med. 160:1009, 2000--FP News 2/1/01)
    2. Ginseng has been ass'd with psychiatric sx at doses > 15g/d
  5. Milkweed (Gymnema sylvestre)
    1. Uncontrolled studies done in India have suggested a hypoglycemic effect (e.g., J. Ethnopharm. 30:295, 1990 and 30:281, 1990--FP News)
    2. Double-blind study initiated early 2001 at Univ. of Utah