 |
| |
 | | Drug Therapy | |
- Use patient characteristics and preferences to set treatment goals in the initial choice of pharmacologic agent.
- Adjust diabetes medications as needed to achieve target level of glycemic control.
- Consider using a combination of insulin and oral agents if oral agents do not achieve the desired level of glycemic control.
- Consider using other insulin regimens if oral agents and bedtime insulin combined do not achieve the desired level of glycemic control.
- Aim for optimal glucose control to reduce risk of microvascular and neuropathic outcomes in patients with type 2 diabetes.
- Treat hypertension aggressively to reduce the risk of adverse microvascular (e.g., retinopathy, nephropathy) and macrovascular (e.g., MI, stroke) outcomes.
- Treat hyperlipidemia with diet and pharmacologic agents to reduce the risk of adverse macrovascular outcomes.
- Consider use of aspirin therapy for primary and secondary prevention of cardiovascular disease in all patients with diabetes, unless there are specific contraindications.
- Take steps to prevent and treat diabetic nephropathy to reduce the risk of progression to end-stage renal failure in patients with type 2 diabetes.
- Consider treating painful neuropathy with tricyclic antidepressants, carbamazepine, gabapentin, capsaicin, or duloxetine.
| | Pharmacologic Agents for Diabetes Mellitus, Type 2 (table)
|
|
Use patient characteristics and preferences to set treatment goals in the initial choice of pharmacologic agent.  |
- Choose agents empirically.
- Aim treatment strategies to target glucose control to achieve HbA1c <7% referenced to a nondiabetic range of 4% to 6% using a Diabetes Control and Complication Trial-based assay.
- Aim treatment strategies at maximizing efficacy and safety while considering patient preferences for treatment.
- Consider all of the following factors when making individual treatment decisions:
- Minimization of weight gain
- Minimization of insulin injections
- Minimization of patient effort
- Avoidance of hypoglycemia
- Minimization of cost
- Consider metformin as a first-line agent because it causes less hypoglycemia and weight gain, along with possible improvements in cardiovascular risk.
- Consider other oral agents, such as sulfonylureas, thiazolidinediones, and DPP-IV inhibitors, as reasonable first-line agents, although some are costly and the long-term benefits of these drugs have not been well studied.
- See table Pharmacologic Agents for Diabetes Mellitus, Type 2.
- See table Dosages for Various Sulfonylureas.
| Background | Back to top
|
Adjust diabetes medications as needed to achieve target level of glycemic control. |
- Maximize dosage of agent before adding additional agents.
- Be aware that the response to escalating from submaximal to maximal doses, particularly for metformin and sulfonylureas, is usually limited.
- Given minimal differences in efficacy and limited data about long-term outcomes, use combinations of oral agents based on patient preference, provider familiarity, and consideration of issues such as side effect profiles and costs.
- Consider adding exenatide to oral agents in patients who have not achieved adequate glycemic control on a thiazolidinedione, metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea.
- Begin exenatide, 5 µg sc bid within 60 minutes before the morning and evening meal
- Decrease the dose of the sulfonylurea agent to reduce the risk of hypoglycemia; a dose reduction for metformin or the thiazolidinedione is usually not needed
- After 1 month of therapy, increase the dose of exenatide to 10 µg sc bid
- See table Pharmacologic Agents for Diabetes Mellitus, Type 2.
- See table Dosages for Various Sulfonylureas.
| Background | Back to top
|
Consider using a combination of insulin and oral agents if oral agents do not achieve the desired level of glycemic control.  |
- Consider bedtime insulin plus daytime sulfonylurea (BIDS):
- Maximize doses of sulfonylurea in the morning
- Begin insulin NPH or insulin glargine, 10 units at bedtime; titrate doses over time to achieve target glycemic control (morning fasting glucose ~80 to 120 mg/dL).
- Alternatively, bedtime insulin plus metformin:
- After stopping all other oral agents begin metformin, 1000 mg bid, and an intermediate-acting insulin at bedtime equal to their fasting glucose level in mmol/L (conversion: glucose in mg/dL·18)
- Titrate insulin rapidly because hypoglycemia is relatively uncommon with this combination of agents, e.g., a regimen which calls for increasing the insulin dose by 4 units/d if the fasting glucose level is >8 mmol/L (144 mg/dL) on three consecutive measurements and by 2 units/d if the fasting glucose is >6.6 mmol/L (120 mg/dL) on 3 consecutive days.
- See table Pharmacologic Agents for Diabetes Mellitus, Type 2.
- See table Dosages for Various Sulfonylureas.
| Background | Back to top
|
Consider using other insulin regimens if oral agents and bedtime insulin combined do not achieve the desired level of glycemic control. |
- Continue preexisting oral agents such as metformin and thiazolidinediones for their insulin-sensitizing and insulin-sparing effects.
- Consider any of the possible multiple combinations:
- Twice-daily NPH or Lente injection
- Twice-daily split-mixed (self-mixed NPH or Lente with regular) injection or insulin 70/30 before breakfast and dinner
- Multiple daily injections of regular insulin
- Once a day injection of insulin glargine
- Once or twice a day injection of insulin detemir
- Start with a dose of 0.10 to 0.15 units/kg divided in one or two doses.
- Adjust dosages based on home glucose monitoring at 2-week intervals; typically, increase or decrease doses in 10% increments.
- If glycemic control remains inadequate, consider adding pramlintide.
- Begin pramlintide at a dose of 60 µg sc just before each major meal
- Reduce the dose of rapid-acting, short-acting, or fixed-mix pre-meal insulin by 50%
- Monitor blood glucose frequently before and after meals and at bedtime
- If the patient has no nausea, increase maintenance dose to 120 µg; if nausea develops and persists, decrease to 60 µg
- When pramlintide dose is stabilized, adjust insulin dose to optimize glycemic control and avoid hypoglycemia
- See table Onset and Mechanisms of Action of Various Types of Insulin.
| Background | Back to top
|
Aim for optimal glucose control to reduce risk of microvascular and neuropathic outcomes in patients with type 2 diabetes.  |
- Improve glucose control and aim to achieve as close to normoglycemia as possible to minimize the risk of complications such as retinopathy, nephropathy, and neuropathy.
| Background | Back to top
|
Treat hypertension aggressively to reduce the risk of adverse microvascular (e.g., retinopathy, nephropathy) and macrovascular (e.g., MI, stroke) outcomes. |
- Treat to a target blood pressure of 130/80 mmHg. Although there are no data suggesting exactly when to start therapy, most trials have enrolled subjects whose initial blood pressure was >140/90 mmHg.
- Initiate treatment of hypertension with thiazide diuretics, ACE inhibitors, or ARBs.
- Recognize that most patients with type 2 diabetes will require multiple agents (the use of three or more agents is common) to achieve the target blood pressure goal.
- Consider β-blockers and calcium-channel blockers as agents if combinations of the initial agents (thiazide diuretics, ACE inhibitors, ARBs) do not control blood pressure or are not tolerated.
- Reserve α-blockers for patients who cannot achieve adequate blood pressure control using other agents.
- Consider cost, patient preferences, side-effect profile, and especially comorbidities to make individualized decisions about therapy, e.g., using:
- A β-blocker in patients who have had a MI
- A diuretic, ACE inhibitor, and β-blocker in patients with congestive heart failure
- An ACE inhibitor or ARB in patients with proteinuria or overt diabetic nephropathy
- See module Essential Hypertension.
| Background | Back to top
|
Treat hyperlipidemia with diet and pharmacologic agents to reduce the risk of adverse macrovascular outcomes.  |
- 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.
- See the drug therapy section in the module Lipid Disorders.
| Background | Back to top
|
Consider use of aspirin therapy for primary and secondary prevention of cardiovascular disease in all patients with diabetes, unless there are specific contraindications. |
- For secondary prevention, initiate aspirin therapy in patients with diabetes and a history of cardiovascular disease.
- For primary prevention, consider aspirin therapy in patients with type 2 diabetes who are at increased risk for cardiovascular disease, including those over age 40 and those with additional risk factors such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.
| Background | Back to top
|
Take steps to prevent and treat diabetic nephropathy to reduce the risk of progression to end-stage renal failure in patients with type 2 diabetes. |
- Treat hypertension aggressively to a target blood pressure of 130/80 mmHg.
- In patients with microalbuminuria or overt proteinuria, consider treatment with an ACE inhibitor or angiotensin II receptor blocker independent of blood pressure control.
- While the optimal doses of these agents have not been defined, consider titration to the maximum tolerated dose.
- Monitor proteinuria, serum creatinine, and serum potassium while on therapy.
| Background | Back to top
|
Consider treating painful neuropathy with tricyclic antidepressants, carbamazepine, gabapentin, capsaicin, or duloxetine. |
- Individualize management options based on patient preferences and comorbidities:
- Consider starting with tricyclic antidepressants (e.g., 25 mg nortriptyline at bedtime) and titrate based on pain relief but watch for anticholinergic side effects, particularly in the elderly.
- Consider topical capsaicin cream but watch for a burning senstion early in treatment.
- Consider antiepileptics such as carbamazepine and gabapentin in patients unable to tolerate tricyclic antidepressants or topical medications.
- Individualize treatment based on cost and patient comorbidities and preferences.
| Background | Back to top
| | | FAQs |
|
| Sandeep Vijan, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.
Darren B. Taichman, MD, PhD, Editor, PIER, has received grant support from Actelion Pharmaceuticals Ltd , and honoraria for continuing medical education grand rounds and lectures given. |
|
|
|
The information included herein should never be used as a substitute
for clinical judgment and does not represent an official position of
ACP. Because all PIER modules are updated regularly, printed web pages
or PDFs may rapidly become obsolete. Therefore, PIER users should
compare the date of the last update on the website with any printout
to ensure that the information being referred to is the most current
available.
|
PIER is copyrighted (c) 2010 by the American College of Physicians,
190 N. Independence Mall West, Philadelphia, PA 19106-1572, USA.
|
|
|
Diabetes Mellitus, Type 2
