DM Full Guideline (2010) - VA/DoD Clinical Practice Guidelines Home

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EVIDENCE TABLE
VA/DoD Clinical Practice Guideline
for the Management of Diabetes Mellitus
Recommendation Sources LE QE SR
1 Choice of drug must be based on a variety of clinical factors Work Group consensus III Poor I
and individual patient characteristics, including
predisposition to adverse effects, the degree of
hyperglycemia
2 Metformin (preferred) or sulfonylurea as first line for most
patients
Bolen et al., 2007 I Good A
3 TZDs, alpha-glucosidase inhibitors, meglitinides, DPP-4 Work Group Consensus II-1 Fair B
inhibitors, and GLP-1 agonists as alternative agents for
patients unable to use metformin or sulfonylureas due to
contraindications, adverse effects, or other reasons
4 Insulin should be considered in any patient with extreme Work Group Consensus II-1 Fair B
hyperglycemia or significant symptoms; even if transition
to therapy with oral agents is intended as hyperglycemia
improves
5 Patients and their families should be instructed to recognize Work Group Consensus III Poor I
signs and symptoms of hypoglycemia and its management
LE-Level of Evidence; QE = Quality of Evidence; SR = Strength of Recommendation (see Appendix A)
J-2. COMBINATION THERAPY (Add-on)
BACKGROUND
When initial therapy no longer provides adequate glycemic control, addition of a drug from another class rather than
substitution (reserve substitution for intolerance/adverse effect to a drug) is usually necessary. Combination of two
anti-hyperglycemic drugs has the benefit of reducing hyperglycemia by working on different mechanisms that cause
hyperglycemia (refer to Figure G-2). Although the evidence is clear on the relative efficacy of the various
medications, their usage needs to be guided by clinical practice. In reality, not all combinations of drugs used in
practice have evidence. Additionally, the data are limited on comparison of different combination regimens that
assess which combination is preferred.
Several factors should be considered when selecting combination therapy. These factors include, but are not limited
to the following: how much the HbA 1 c needs to be reduced, tolerability of an agent, relative or absolute
contraindications a patient may have to using a particular agent, barriers to proper administration. Because of all
these factors, several options for combination therapy should be available.
RECOMMENDATIONS
1. Metformin + sulfonylurea is the preferred oral combination for patients who no longer have adequate
glycemic control on monotherapy with either drug. [A]
2. Other combinations (TZDs, AGIs, meglitinides, DPP-4 inhibitors, and GLP-1 agonists) can be considered
for patients unable to use metformin or a sulfonylurea due to contraindications, adverse events, or risk for
adverse events (see Appendices G-2 and G-3). [B]
3. Addition of bedtime NPH or daily long-acting insulin analog to metformin or sulfonylurea should be
considered, particularly if the desired decrease in HbA 1 c is not likely to be achieved by use of combination
oral therapy. [A]
4. Patients and their families should be instructed to recognize signs and symptoms of hypoglycemia and its
management. [I]
DISCUSSION
The systematic review by the Agency for Healthcare Research and Quality found that combination therapy with
TZDs, SU, metformin and repaglinide were additive and provided an additional 1% decrease in HbA 1 c over
Module G: Glycemic Control Page 57