TOC  |  ENDO

Type 2-Diabetes Mellitus Management  

Pharmacology Rx for Diabetes Mellitus  

REF:   DiabetesDx2011.pdf   |  DiabetesRx2011Summary.pdf  |   DiabetesRx2011.pdf    

Diabetes Mellitus       REF: ACP PIER 2011 | ACP Medicine Best Dx/Best Rx 2007    |   DM Care 2007   | DM Care 2009    

  DX |  DM RX  |  Protocol for acute Rx of hyperglycemia | Diabetic Ketoacidosis | DM Complications |
  Perioperative Rx of DM  | Hyperglycemia Rx in Hospital   ||  Hypoglycemia Rx  
Diagnosis:      Ref:  DiabetesDx2011.pdf   |  DiabetesRx2011Summary.pdf  |   DiabetesRx2011.pdf     

Sx of hyperglycemia, as: 
Polydipsia, polyphagia, polyuria (3P's), weight loss & altered mental status and visual changes.
Other Presentations: Pain—peripheral neuropathy; Weakness; Blurred vision; Central obesity; Recurrent infections, e.g., vaginitis;  Resting tachycardia and orthostatic dizziness; Early satiety, bloating, nausea, vomiting.  

Look for:

  • Acute manifestations of hyperglycemia, such as dehydration
  • Chronic manifestations of microvascular and macrovascular disease, such a retinopathy, nephropathy, peripheral neuropathy, and peripheral vascular disease
  • Signs of autonomic nervos system disease such as resting tachycardia and orthostasis


Current 2011 criteria for the diagnosis of diabetes mellitus

  • A1C > 6.5%.
  • Fasting plasma glucose (FPG) > 126 mg/dl (7.0 mmol/l).
  • 2-h plasma glucose > 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test (OGTT).
  • Random plasma glucose > 200 mg/dl (11.1 mmol/l) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis,
    - associated with symptoms (polyuria, polydipsia, unexplained weight loss)

- Any of these criteria are sufficient for diagnosis, but each should be confirmed on a separate day.


Follow Up of Diabetes Control:  

A1C - a reasonable A1C goal for many nonpregnant adults is <7%.

  • Perform the A1C test at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control).
  • Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals.

Blood Pressure goal is < 130/80

Cholesterol goal is LDL cholesterol < 100; HDL cholesterol > 50 mg/dl, and triglycerides <150 mg/dl)

Antiplatelet agents (Aspirin) Rx

  • Consider aspirin therapy (75.162 mg/ day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk >10%). This includes most men >50 years of age or women >60 years of age who have at least one additional major risk factor (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria).

ACE inhibitors or ARB Rx  

  • In the treatment of the nonpregnant patient with micro- or macroalbuminuria, either ACE inhibitors or ARBs should be used.
  • In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy.
  • In patients with type 2 diabetes, hypertension, and microalbuminuria, both ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria.
  • In patients with type 2 diabetes, hypertension,macroalbuminuria, and renal insufficiency (serum creatinine 1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy.

Cholesterol goal is LDL cholesterol < 100; HDL cholesterol > 50 mg/dl, and triglycerides <150 mg/dl     

Obtain an annual fasting lipid profile, including low-density lipoprotein (LDL) cholesterol, triglyceride, high-density lipoprotein, and total cholesterol levels, and apply the following treatment criteria:

  • For secondary prevention, begin all patients with type 2 diabetes on statins, regardless of LDL and total cholesterol levels
  • For primary prevention, consider statin therapy in patients over age 40 with one other cardiovascular risk factor, regardless of baseline LDL cholesterol levels
  • Maintain serum LDL cholesterol levels at < 100 mg/dL; in patients with diabetes and cardiovascular disease, it is reasonable to attempt to achieve an LDL cholesterol level <70 mg/dL
  • For patients with low levels of HDL cholesterol (<40 mg/dL) and low or normal LDL levels, consider the use of gemfibrozil to reduce risk of macrovascular disease
  • Use niacin therapy cautiously because niacin can increase serum glucose
  • Be especially vigilant for the development of rhabdomyolysis and hepatitis in patients taking both a statin and gemfibrozil


Classification of Diabetes Mellitus:
PRIMARY

  • Type 1 diabetes mellitus - IDDM
  • Type 2 diabetes mellitus - NIDDM
  • Gestational diabetes mellitus

SECONDARY

  • Diabetes caused by pancreatic disease
    Tumor induced hypoglycemia
  • Diabetes caused by hormonal abnormalities
  • Drug- or chemical-induced diabetes
  • Diabetes caused by insulin receptor abnormalities
  • Diabetes associated with genetic syndromes
  • Diabetes of other causes

 

REF: ACP Diabetic Care Book 2007 | ACP PIER 2011 | ACP Medicine Best Dx/Best Rx 2006
Rx of Diabetes Melllitus                  See also Protocol for acute Rx of hyperglycemia  |  Diabetic Ketoacidosis 

* American Diabetes Association goals

  • Preprandial capillary whole blood glucose levels: 90–130 mg/dl
  • Postprandial peak capillary whole blood glucose levels: < 180 mg/dl
  • Hemoglobin A1c (HbA1c) level 7% or lower if feasible without undue risk of hypoglycemia

Nutritional Therapy and Exercise

  • Caloric reduction to produce weight loss (determine intake reduction on basis of degree of obesity and with dietitian's help)
  • Diet < 30% total fat, < 10% saturated fat, < 10% polyunsaturated fat, 10%–15% monounsaturated fat, 10%–20% protein, 50%–55% carbohydrate
  • Addition of high-fiber foods
  • Awareness of carbohydrates to limit postprandial plasma glucose elevation
  • Gradual increase in aerobic exercise

Medications for Diabetes Mellitus           Ref: DiabetesMeds2011.html    

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase)        | Biguanides (Metformin/Glucophage)
Thiazolidinediones
(Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide)
a-Glucosidase inhibitors
(Acarbose/Precose, Miglitol/Glyset)      | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc)
DPP IV Inhibitors
 (Vildagliptin/Galvus, Sitagliptin/Januvia PO)  | Insulin, etc  Rx
, New Inhaled Insulin (Exubera)   

       
Correlation of HgA1c to Average Blood Glucose
  •  6% - 135 mg/dL |  7% - 170 mg/dL  |   8% - 205 mg/dL  |   9% - 240 mg/dL  |  10% - 275 mg/dL  |  11% - 310 mg/dL  | 12% - 345 mg/dL
    Each 1% above 6% add 35 mg/dl to the base 135 mg/dL.


Pharmacology Rx of Diabetes Mellitus

Pharmacologic Therapy 2007

Some suggested to begin with monotherapy, as metformin (Glucophage) if no contraindications;
if response is not satisfactory after maximal dose, may add additional DM drug.  

* Begin with monotherapy; if response is not satisfactory, add additional drug.

ORAL DM MEDICATIONS:

A. Insulin Secretagogues - stimulates pancreatic secretion of insulin, which in turn decreases hepatic glucose production and enhances the uptake of glucose by muscle.

Pancreas

a. Sulfonylureas Secretagogues
  • Mechanism of Action: stimulate insulin secretion from the pancreas.
  • Efficacy: Lower A1c by 1-2% points.
  • Adverse Effects: weight gain and hypoglycemia.
  • Caution: These medications are metabolized by the liver and cleared by the kidney (with the exception of glimepiride, which is excreted both renally & hepatically) and should therefore be used cautiously in patients with impaired hepatic or renal function. They may cause prolonged hypoglycemia in cases of renal failure. They should be used at low dosages in the elderly.

1) First Generation of Sulfonylureas
- largely replaced by 2nd generation sulfonylureas because they are cleared hepatically, and should be avoided in patients with abnormal liver function.

  • Diabenese/Chlorpropamide (1st generation) Duration > 24hours.
    100-250 mg 1-3 tab/d; 100-250 mg tab
  • Orinase /Tolbutamide (1st generation) Duration 10-12 hours.
    250-500 mg tab 1-3x/d
  • Tolinase/Tolazamide (1st generation) Duration 12-24 hours.
    100-500 mg tab -2x/d; 100-250-500 mg tab.
  • Dymelor/Acetohexamide 500-750 mg once or divided.

2) Second Generation of Sulfonylureas
- avoid using in patients with impaired renal function (creat clearance <60 mL/min) or who are elderly.
- side effects are hypoglycemia, weight gain

  • Glipizide (Glucotrol) Duration 12-24 hours
    Dose: lowest effective single dose, 5mg, Usually dose 5-10 mg 1-2 tab BID (Max 40 mg/day)
  • Glipizide (GI therapeutic system) Glucotrol XL 5-10mg tab once/day (Max 20 mg/day)
    Dose: lowest effective single dose, 5 mg; daily max, 20 mg
  • Glyburide (Micronase, Diabeta) - (2nd generation) Duration 12-24 hours
    Dose: lowest effective single dose, 1.25 mg; Usually dose 1.25-2.5-5 mg 1-2 tab BID (Max 20 mg/day)
  • Micronized glyburide (Glynase)
    Dose: lowest effective single dose, 1.5 mg; daily max, 6 mg
  • Glimepiride (Amaryl) (3rd generation) Duration 24 hours
    Dose: lowest effective single dose, 0.5 mg; 1,2,4 mg tab/day. Start 1-2 mg/d, usual maintenance dose is 1-4mg once/d (Max: 8mg/d)
  • Gliclazide/ Diamicron 80-160 mg daily, max 320 mg PO daily.
    Modified release Diamicron MR 30 mg PO daily, mas 120 mg daily


Dosages for Various Types of Sulfonylureas

1st Generation Sulfonylureas:

  • Acetohexamide (Dymelor) 250-1500 mg/d qd-bid
  • Chlopropamide (Diabinese) 100-750 mg/d qd
  • Tolazamide (Tolinase) 100-1500 mg/d qd-bid
  • Tolbutamide (Orinase) 250-3000 mg/d bid-qid

_______________________________________________________  

2nd Generation Sulfonylureas:

  • Glimepiride (Amaryl) 1-8 mg/d qd
  • Glipizide (Glucotrol) 2.5-40 mg/d qd-bid
  • Glipizide-GITS (Glucotrol XL) 5-20 mg/d qd
  • Glyburide (Diabeta, Micronase) 1.25-20 mg/d* qd-bid
  • Micronized glyburide (Glynase/PresTab) 1.5-12 mg/d qd-bid

   

b. Non-sulfonylurea Secretagogues (Meglitinides)
  • Mechanism of Action: Rapidly stimulate insulin secretion from the pancreas.
  • Efficacy: Lower A1c by 0.5 --2% points.
  • * They are cleared hepatically and may be used in patients with renal impairment.
  • * Consider using in patients with modest postporandial hyperglycemia and who have irregular timing of meals.
  • Benefits: less weight gain and hypoglycemia compared with sulfonylureas.
  • Caution: These medications are metabolized by the liver and should therefore be used cautiously in patients with impaired hepatic function. They may cause prolonged hypoglycemia in cases of renal failure. They should be used at low dosages in the elderly.
  • Prandin (Repaglinide) Duration 4-6 hours
    Dose: 0.5 - 1 - 2 mg tab TID within 30 min before meals (Max 16 mg/day)
  • Starlix (Nataglinide) Duration 4 hours
    Dose: 120 mg ac

   

c. Oral Dipeptidyl Peptidase IV (DPP IV) Inhibitors for type 2 Diabetes
- blocks inactivation of GI peptide hormones DPP IV.
  • DDP-4 enzyme naturally breaks down the GI hormone called GLP-1 (Glucagon-Like Peptide), which promotes the synthesis and release of insulin when food is consumed, lowers levels of glucagon, induces satiety by slowing gastric emptying, and possibly stimulates beta-cell growth & neogenesis.
  • Mechanism of Actions: Inhibits degradation of DPP IV (the enzyme that degrades endogenously secreted incretins, including glucagons-like peptide-1 and glucose-dependent insulinotropic polypeptide). Higher levels of these incretin hormones lead to increased insulin secretion & suppression of glucagons secretion.
  • Benefits: weight neutral. The mechanism of action involves glucose-dependent insulin secretion. It does not cause hypoglycemia when used as monotherapy.
  • Adverse Effects: Metabolized in the liver but excreted largely unchanged in the urine; the dosage needs to be reduced by 50-75% in pts with renal insufficiency. Most common adverse effects include nasopharyngitis and headache.
  • Sitagliptin (Januvia) 100 mg PO daily; 25-50 mg/d in renal impairment.
  • Vildagliptin (Galvus)     

   

B. Insulin Sensitizers

Agents that enhance insulin action work through several mechanisms. They miay inhibit glucose absorption, inhibit hepatic gluconeogenesis and glycogenolysis, or increase glucose uptake in fat and muscle.

Liver

Biguanides

  • Metformin (Glucophage) Duration 12-18 hours
    Dose: 500 mg/day up to 1000 mg BID  
  • Metformin extended release
    Dose: lowest usual dosage, 500 mg q.d.; maximum effective dosage, 1,000 mg b.i.d.; + Cost/mo: $48

  • Good first-line agent for overweight pts. Consider using in pts already on a secretagogue who need additional glucose lowering. Avoid in patients with renal or hepatic impairment or CHF patients class III-IV.
  • Mechanism of Action: Inhibits hepatic gluconeogensis and to a leser extent glycogenolysis. Also enhances insulin sensitivity in muscle and fat.
  • Efficacy: Lowers A1c by 1-2% points.
  • Benefits: Does not cause hypoglycemia when used as monotherapy and can cause weight loss.
  • Adverse Effects: Lactic acidosis is a rare but potentially fatal adverse effect, esp if baseline renal function is abnormal or if an acute insult is affecting kidneys, such as dehydration, major surgery, chronic heart failure, or administration of radiocontrast agents.
  • Metformin should not be prescribed if the serum creat is > 1.5 mg/dL in men or > 1.4 mg/dL in women.

   

Muscle and Fat

Thiazolidinediones ("Glitazones")

  • Mechanism of Action: enhance insulin sensitivity in muscle & fat by increasing the expression of glucose transporters.
  • Efficacy: lower A1c by 1-2%;
  • Benefits: Do not cause hypoglycemia when used as monotherapy. Lower the triglycerides, raise the HDL levels.
  • Adverse effects: weight gain due to fluid retention, peripheral edema, may worse CHF. Recent report of increase cardiovascular morbidity.
  • Avoid these drugs in patients with abnormal hepatic function ALT>2.5X normal, CHF class III or IV patients.
  • If liver function test as ALT >2.5x normal, these agents should not be used.
  • The agent Troglitazone was withdrawn from US market due to hepatotoxicity.
  • * NEJM May 2007;356:1
    In the rosiglitazone (Avandia) group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 (as 0.43% vs 0.36% in small trials, 0.57% vs 0.34% in DREAM trial, 1.85% vs 1.44% in ADOPT trial), and for death from cardiovascular causes was 1.64 (as 0.38% vs 0.19% in small trials, 0.51% vs 0.38% in DREAM trial, 0.14% vs 0.18% in ADOPT trials).

  • Pioglitazone/Actos Duration days to weeks  
    Dose: 15-30-45 mg tablet once daily (Max 45 mg/day)

    JAMA. Sep 12, 2007;298:1180-1188
    Data Synthesis: A total of 19 trials enrolling 16 390 patients were analyzed. Study drug treatment duration ranged from 4 months to 3.5 years. Death, myocardial infarction, or stroke occurred in 375 of 8554 patients (4.4%) receiving pioglitazone (Actos) and 450 of 7836 patients (5.7%) receiving control therapy (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72-0.94; P = .005). Progressive separation of time-to-event curves became apparent after approximately 1 year of therapy. Individual components of the primary end point were all reduced by a similar magnitude with pioglitazone treatment, with HRs ranging from 0.80 to 0.92. Serious heart failure was reported in 200 (2.3%) of the pioglitazone-treated patients and 139 (1.8%) of the control patients (HR, 1.41; 95% CI, 1.14-1.76; P = .002). The magnitude and direction of the favorable effect of pioglitazone on ischemic events and unfavorable effect on heart failure was homogeneous across trials of different durations, for different comparators, and for patients with or without established vascular disease. There was no evidence of heterogeneity across the trials for either end point (I2 = 0%; P = .87 for the composite end point and I2 = 0%; P = .97 for heart failure).
    Conclusions:   Pioglitazone (Actos) is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality.
  • Rosiglitazone/Avandia Duration days to weeks
    Dose: 4 mg 1-2x/day (Max 8 mg/day) - see warning!

    JAMA. Sep 12, 2007;298:1189-1195
    Results: Rosiglitazone (Avandia) significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I2 = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality).
    Conclusion:   Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone (Avandia) use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.
  • Avandamet (Rosiglitazone/metformin) 1-2-4 mg/500mg tablets

   

Gastrointestines

Alpha-Glucosidase Inhibitos

  • * Consider primarily in postprandial hyperglycemia patients.; may be used in combination with insulin sensitizers or sulfonylurea secretagogues but no non-sulfonylurea secretagogues.
  • Mechanism of Actions: Delay carbohydrate absorption by competitively block the enzyme alphs-glucosidase in the brush borders of the small intestine, resulting in absorption of carbohydrates in the mid and distal small intestine.
  • Efficacy: lower A1c by 0.5 - 1 % points.
  • Benefits: reduces the postprandial rise in blood glucose
  • Adverse Effects: should not be used in severe hepatic or renal impaired paitnet or in those with GI disease.
    GI side effects can be severe and include bloating, abd cramps, diarrhea, and flatulence.

  • Acarbose/Precose Duration 2-3 hours
    Dose: 25- 50- 100 mg tid with first bite of meal. Initially 25 mg 1x/d x2wks, then bid x2wks, then tid x2months, then may increase to 50 mg tid..
  • Miglitol/Glyset Duration 2-3 hours
    Dose: 25-50-100 mg tid with first bite of meal. (Max 300 mg/day)

   

B. Insulin Sensitizers

Agents that enhance insulin action work through several mechanisms. They miay inhibit glucose absorption, inhibit hepatic gluconeogenesis and glycogenolysis, or increase glucose uptake in fat and muscle.

Oral Dipeptidyl Peptidase IV Inhibitors for type 2 Diabetes
- blocks inactivation of GI peptide hormones DPP IV.

  • DDP-4 enzyme naturally breaks down the GI hormone called GLP-1 (Glucagon-Like Peptide), which promotes the synthesis and release of insulin when food is consumed, lowers levels of glucagon, induces satiety by slowing gastric emptying, and possibly stimulates beta-cell growth & neogenesis.
  • Mechanism of Actions: Inhibits degradation of DPP IV (the enzyme that degrades endogenously secreted incretins, including glucagons-like peptide-1 and glucose-dependent insulinotropic polypeptide). Higher levels of these incretin hormones lead to increased insulin secretion & suppression of glucagons secretion.
  • Efficacy: lower A1c by 0.7 - 1.4% points.
  • Benefits: weight neutral. The mechanism of action involves glucose-dependent insulin secretion. It does not cause hypoglycemia when used as monotherapy.
  • Adverse Effects: Metabolized in the liver but excreted largely unchanged in the urine; the dosage needs to be reduced by 50-75% in pts with renal insufficiency. Most common adverse effects include nasopharyngitis and headache.
  • JANUVIA™ (sitagliptin phosphate), the first and only a new breakthrough class of DPP-4 inhibitor available in the United States for the treatment of type 2 diabetes, as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve blood sugar (glucose) control in patients with type 2 diabetes when diet and exercise is not enough.
  • JANUVIA enhances a natural body system called the incretin system, which helps to regulate glucose by affecting the beta cells and alpha cells in the pancreas. Through DPP-4 inhibition, JANUVIA works only when blood sugar is elevated to address diminished insulin due to beta-cell dysfunction and uncontrolled production of glucose by the liver due to alpha-cell and beta-cell dysfunction.
  • " Helps control glucose without weight gain or an increased risk of hypoglycemia
  • " The incidence of selected gastrointestinal (GI) adverse reactions in patients treated with JANUVIA 100 mg vs placebo was as follows: abdominal pain (2.3%, 2.1%); nausea (1.4%, 0.6%); and diarrhea (3.0%, 2.3%).

  • Sitagliptin (Januvia)  Duration 24 hours
    Dose: 100 mg/day with or without food; decrease dosage to 25 or 50 mg/day in patients with moderate or severe renal insufficiency or with end-stage renal disease(ESRD) requiring hemodialysis or peritoneal dialysis.
  • Janumet (Sitagliptin/metformin) 50/500 or 50/1000 mg tab 1 tab bid PO  
  • Vildagliptin (Galvus)  

   

SUBCUTANEOUS DM MEDICATIONS - Injectable Gastrointestinal Hormone Agents

New Subcutaneous diabetic medications other than insulin

GLP (Glucagon-Like Peptide) Analogues:

Byetta (Exenatide) 5 mcg subc bid for type 2 diabetics

  • - 5 mcg subc bid, within 1 h before the morning & evening meals, may increase to 10 mcg bid subc after 1 month.
  • - It is available in a pen that delivers 60 fixed doses of either 5 mcg or 10 mcg for 1 month supply.
  • - It is a long-acting analogue of gut incretin hormone GLP-1 (Glucagon-like-peptide-1), called incretin mimetics (analog)
  • for the treatment of type 2 diabetes (Not approved for type 1 diabetes).
  • - It exhibits many of the same effects as GLP-1, secreted in response to food intake, has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood sugar.
  • - It [as gut incretin hormone GLP-1 (Glucagon-like-peptide-1), called incretin mimetics]
  • reduces fasting & postprandial glucose by
    > increasing glucose-stimulated insulin secretion from pancreas,
    > decreasing glucagon secretion,
    > slowing gastric emptying &
    > reducing appetite.
  • - Nausea is a frequent side effect (44%), vomiting & diarrhea (13%); potential hypoglycemia.
  • - It may be used in combination with metformin, sulfonylurea or both.
  • * More than 80% of treated patients with Byetta (Exenatide) lost weight 3-5 lbs at 30 weeks !!!

Amylin Analogues:

Symlin (pramlintide) 15 mcg subc before meal for type 1 & 2 diabetics

  • - 15 mcg subc before meal, titrate by 15 mcg increments up to maintenance 30-60 mcg as tolerated in Type 1 diabetes.
  • - In type 2 diabetes initiate 60 mcg subc before meals and increase up to 120 mcg as tolerated.
  • - a synthetic analog of the pancreatic neuroendocrine hormone amylin, it is secreted from beta cells with insulin.
  • - Reduce preprandial insulin by half
  • - The drug slows gastric emptying and decreases appetite and glucagon secretion after meals.

   

Combination Oral Diabetic Therapy

* Use same drugs as with monotherapy, beginning with the lowest suggested dose of each

  • Sulfonylurea + metformin
  • Sulfonylurea + thiazolidinedione
  • Metformin + thiazolidinedione
  • Metformin + repaglinide
  • Repaglinide + thiazolidinedione
  • ?-Glucosidase inhibitors + any other drug
  • Sulfonylurea + metformin + thiazolidinedione
  • Metformin + thiazolidinedione + repaglinide or nateglinide
  • Insulin + any other drug

   

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase)  
Non-Sulfonylureas Secretagogues: Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide)
Biguanides (Metformin/Glucophage)
Thiazolidinediones
(Pioglitazone/Actos, Rosiglitazone/Avandia) |
a-Glucosidase inhibitors
(Acarbose/Precose, Miglitol/Glyset)  
GLP Analogues
(Exenatide/Byetta, Pramlintide/Symlin Subc)
DPP IV Inhibitors
 (Vildagliptin/Galvus, Sitagliptin/Januvia PO)  |
Insulin, etc  Rx
, New Inhaled Insulin (Exubera)  
INSULIN THERAPY  
Insulin Therapy

* One daily injection of long-acting insulin (NPH, glargine, or detemir)

  • Dose: 10 U or 0.15 U/kg initially; increase by 2 U once or twice weekly until fasting glucose ? 120 mg/dl; or increase by 6–8 U weekly until fasting glucose ? 140 mg/dl, then increase by 2–4 U weekly until fasting glucose ? 120 mg/dl

* Regular or rapid-acting insulin before meals if postprandial glucose not controlled

  • Take regular insulin 30 min before meal
  • Take rapid-acting insulin just before or just after meal
INSULIN treatment       

Rapid-Acting  |  Short-Acting  |  Intermediate-Acting  |  Long-Acting  | Combination  |   New Inhaled Insulin  | Non-insulin subc  


RAPID-ACTING:  as Humalog & Novolog insulin

  • Onset: 10-30 min  |  Peak: 30-60 min  |  Duration:  3-5 h    (Medical Letter September 2002)

Humalog insulin analog is faster but shorter duration action than Human regular insulin.  Use within 15 min before meals.

Injection, solution, aspart, human:

  • NovoLog®: 100 units/mL (10 mL vial)

  • NovoLog® [PenFill®]: 100 units/mL (3 mL cartridge)

Injection, solution, lispro, human:

  • Humalog®: 100 units/mL (1.5 mL cartridge, 3 mL disposable pen, 10 mL vial)


SHORT-ACTING:  Regular insulin

  • Onset: 30-60 min  |  Peak:  1.5-2 h  |  Duration:  5-8 h  

Injection, solution, regular, human:

  • Humulin® R: 100 units/mL (10 mL vial)

  • Novolin® R: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial)

  • Novolin® R [PenFill®]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, solution, regular, human, buffered :

  • * Velosulin® BR [Discontinued]: 100 units/mL (10 mL vial)

Injection, solution, regular, purified pork:

  • Regular Iletin® II: 100 units/mL (10 mL vial)

 


INTERMEDIATE-ACTING:  NPH or Lente insulin

  • Onset: 1-2 h  |  Peak: 4-8 h  |  Duration: 10-20 h

Injection, suspension, lente, human [zinc]:

  • Humulin® L, * Novolin® L [Discontinued]: 100 units/mL (10 mL vial)

  • Injection, suspension, lente, purified pork [zinc]:

  • Lente® Iletin® II: 100 units/mL (10 mL vial) [Discontinued]

Injection, suspension, NPH, human [isophane]:

  • Humulin® N: 100 units/mL (3 mL disposable pen, 10 mL vial)

  • Novolin® N: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial)

  • Novolin® N [PenFill®]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, suspension, NPH, purified pork [isophane]:

  • NPH Iletin® II: 100 units/mL (10 mL vial)

Injection, Levemir [insulin determir (rDNA origin)] subc once or twice daily

  • Onset of action: 2–3 h;  Duration of action: 9–24 hr;  Peak action: variable modest peak: 6–10 hr


Inhaled insulin (Exubera - Pfizer)   - NEW 2006 !                      See  NEJM Inhaled Insulin 2007 article  
Onset of action: 15–30 min; Peak action: 1.5–2 hr; Duration of action: 6–8 hr  
Dose:  1 mg for pts 30-39.9kg, and then add 1 mg for every 20 kg in patient over 40 kg.
Supply: 1-mg and 3-mg blister pakcs.  The 1-mg pack is approximately equivalent to 3 units of subc regular insulin, 3-mg pck is about 8 units of subc regular insulin.
Jan. 27, 2006 — The first inhaled insulin (Exubera) was approved today by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 1 and type 2 diabetes. An inhaled powder form of recombinant human insulin (rDNA), the drug and delivery system is the first new insulin formulation introduced since the discovery of insulin in the 1920s, according to the FDA.
FDA recommends pulmonary function testing at the start of Exuber therapy, at 6 months, and every year thereafter.  
Exubera is used 10-15 min before meals for prandial insulin coverage only; patients still need subc injections of long-acting insulins for basal coverage.
Exubera is contraindicated in patients with preexisting lung disease and in smokers.

 

See also Medications for Diabetes Mellitus  
Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase)  
Non-Sulfonylureas Secretagogues: Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide)
Biguanides (Metformin/Glucophage)
Thiazolidinediones
(Pioglitazone/Actos, Rosiglitazone/Avandia) |
a-Glucosidase inhibitors
(Acarbose/Precose, Miglitol/Glyset)  
GLP Analogues
(Exenatide/Byetta, Pramlintide/Symlin Subc)
DPP IV Inhibitors
 (Vildagliptin/Galvus, Sitagliptin/Januvia PO)  |
Insulin, etc  Rx
, New Inhaled Insulin (Exubera)  

       

2006 General Guidelines for Management of Patients Presenting with High Blood Sugars                    See also  Diabetic Ketoacidosis 

For blood glucose 300 - 500 mg/dl:
  1. Give 10 units Regular or Novolog (Aspart) insulin + 10 units NPH insulin subcutaneously.
  2. Order the following STAT labs the day of the visit:
    " RBS, lytes, BUN, Cr, ketones (add appropriate lab studies if not done recently i.e. non-fasting DM panel (HbA1c, urine Microalbumin, non-fasting HDL, LDL, ALT).
  3. If DCC follow-up is desired, schedule same-day (SDD) appointment for the next working day.
    Phone: 8-327-2440 (Imperial ext. 72440) or Fax a referral: 8-327-2402 (Imperial ext. 72402)
    Order stat FBS, ketones and lytes if abnormal on day of initial visit.
  4. Start oral agent and give diabetes education packet.
    " Order on Health Connect or give prescription for One Touch Ultra glucose meter kit with extra strips (Sure Step, if elderly).
    " Please call DCC or patient may contact the Call Center to schedule for a meter instruction class (60-90 minutes) at DCC
    Imperial Bldg. B Suite 327, # 8-327-2440 (Imperial ext. 72440).
    **It is important that patient is told to bring his/her machine to the class.
  5. Recheck blood sugar before patient is discharged home. Goal: blood sugar <300.
  6. Review with patient the need to force fluids and eat on schedule.


For blood glucose greater than 500 mg/dl  (but glucose less than 700 mg/dL and serum CO2>20):

  1. Give 15 units Regular or Novolog (Aspart) insulin + 10 units NPH insulin subcutaneously.
  2. Order the following STAT labs on the day of the visit: RBS, lytes, BUN, Cr, ketones
    " Add appropriate lab studies if not done recently i.e.,non -fasting DM panel (HbAlc, urine microalbumin, and non-fasting HDL, LDL, ALT).
  3. Start IV hydration with 1 liter normal saline. Give 20 meq KCl p.o. if K+ is <3.5.
    " Blood sugar should be checked hourly.

    " Call DCC 8-327-2440 (Imperial ext. 72440) if assistance is needed.
    During after-hours, send the patient to ED for hydration and further treatment after initial insulin injection.
  4. If DCC follow-up is desired, schedule same-day (SDD) appointment for the next working day.
    Phone: 8-327-2440 (Imperial ext. 72440) or Fax a referral: 8-327-2402 (Imperial ext. 72402)
    Labs to be done before follow-up visit: stat FBS, ketones, and lytes (if abnormal on day of initial visit).
  5. Start oral agent or add insulin if indicated.
    " Give diabetes education packet and encourage pt. to attend MHE classes.
    " Order on Health Connect or give prescription for One Touch Ultra glucose meter kit and extra strips (Sure Step, if elderly).
    " Please call DCC or patient may contact the Call Center to schedule for a meter instruction class (60-90 minutes) at DCC
    Imperial Bldg. B, Suite 327, tie line 8-327-2440 (Imperial ext. 72440). **It is important that patient is told to bring his/her machine to the class.
    " Insulin instruction classes (60 minutes) can also be scheduled at DCC 8-327-2440 (Imperial ext. 72440).
    **Please provide patient with prescriptions for insulin and syringes before discharge. Include a separate written order that notes dose of insulin you want patient to be started on.
  6. Recheck blood sugar before patient is discharged home. Goal: blood sugar <300.
  7. Review with patient the need to force fluids and eat on schedule.


For blood glucose >700 mg/dl or C02 <20,

  • patients should be sent to Emergency Room Department after giving insulin and 20 meq KCL p.o if K+ is <3.5. If patient appears dehydrated, start one liter normal saline IV and transport by ambulance.

Endocrinology (KP Imperial Diabetic Clinic 2-2006)

Infections in Patients with diabetes Mellitus - Johns Hopkins Advanced Studies in Medicine Feb 2006  

       2007


REF: The Washington Manual® of Medical Therapeutics (WashMan™) 2007

HYPOGLYCEMIA Treatment

Isolated episodes of mild hypoglycemia may not require specific intervention. Recurrent episodes require a review of lifestyle factors; adjustments may be indicated in the content, timing, and distribution of meals, as well as medication dosage and timing. Severe hypoglycemia is an indication for supervised treatment. › Readily absorbable carbohydrates (e.g., glucose and sugar-containing beverages) can be administered orally to conscious patients for rapid effect. Alternatively, milk, candy bars, fruit, cheese, and crackers may be adequate in some patients with mild hypoglycemia. Hypoglycemia associated with acarbose or miglitol therapy should preferentially be treated with glucose. Glucose tablets and carbohydrate supplies should be readily available to patients with DM at all times.

  1. IV dextrose is indicated for severe hypoglycemia, in patients with altered consciousness, and during restriction of oral intake. An initial bolus, 20–50 mL of 50% dextrose, should be given immediately, followed by infusion of D5W (or D10W) to maintain blood glucose above 100 mg/dL. Prolonged IV dextrose infusion and close observation is warranted in sulfonylurea overdose, in the elderly, and in patients with defective counterregulation.
  2. Glucagon, 1 mg IM, IV or SC (1/2 life 8 to 18 minutes), is an effective initial therapy for severe hypoglycemia in patients unable to receive oral intake or in whom an IV access cannot be secured immediately. Vomiting is a frequent side effect, and therefore care should be taken to prevent the risk of aspiration. A glucagon kit should be available to patients with a history of severe hypoglycemia; family members and roommates should be instructed in its proper use.
  3. Education regarding etiologies of hypoglycemia, preventive measures, and appropriate adjustments to medication, diet, and exercise regimens are essential tasks to be addressed during hospitalization for severe hypoglycemia.
  4. Hypoglycemia unawareness can develop in patients who are undergoing intensive diabetes therapy. These patients should be encouraged to monitor their blood glucose frequently and take timely measures to correct low values (<60 mg/dL). In patients with very tightly controlled diabetes, slight relaxation in glycemic control and scrupulous avoidance of hypoglycemia can restore the lost warning symptoms.


Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes

The ACCORD Study Group

N Engl J Med 2011; 364:818-828.  March 3, 2011

Conclusions  
As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6%


       2011