Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. (Diabetes Care, Aug. 2006) November 6, 2006
Posted by healthweb in Endocrine, Primary Care.trackback
by Dr. David Weir
This is a summary of the recently published consensus statement on management of type 2 diabetes by the ADA and the European Association for the Study of Diabetes. This statement includes an algorithm for the initiation of medications in diabetic patients. Both the DCCT and the UKPDS studies have shown that improved glycemic control can reduce the complications associated with diabetes. In both type 1 and type 2 diabetes retinopathy, nephropathy, and neuropathy complications are reduced with lower A1C levels.
Goals of therapy:
1. In general an A1C of <7%, but as close to normal (<6%) as
possible without hypoglycemia.
2. If a patients A1C is >7% it’s time to initiate or change therapy.
3. Early intervention: initiating therapy at lower glycemic levels are
associated with lower A1C levels in the long run.
Therapy:
1. Lifestyle interventions:
a. Weight loss and exercise. Expected decrease in A1C of 1-2%.
Although lifestyle changes are difficult for patients to sustain with a high rate of relapse it should be encouraged at every office visit. Weight loss and exercise also improve other risk factors for diabetics, namely blood pressure and lipid profile. Lifestyle changes are cheap and have a favorable side-effects profile. Patients will have improved hyperglycemia with a weight loss of as little as 8 pounds.
2. Medications:
a. Metformin: first line agent, inexpensive. Expected decrease in A1C 1.5
b. Insulin: inexpensive, improved lipid profile. Expected decrease in A1C 1.5-2.5
c. Sulfonylureas: inexpensive. Expected decrease in A1C 1.5
d. TZDs: improved lipid profile. Expected decrease in A1C 0.5-1.4
Other drugs:
e. Alpha-Glucosidase inhibitors: Expected decrease in A1C 0.5-0.8
f. Exenatide (Byetta): weight loss. Expected decrease in A1C 0.5-1
g. Glinides: short duration. Expected decrease in A1C 1-1.5
h. Pramlintide: weight loss. Expected decrease in A1C 0.5-1
Treatment algorithm:
Step 1: Lifestyle interventions and metformin.
-Metformin should be titrated to maximally effective dose (usually
850mg bid) over 1-2 months.
-Consider adding additional medications with persistent symptomatic hyperglycemia.
-Check A1C every 3 months until <7%, then every 6 months.
Step 2: If A1C >7%, add second agent.
-Insulin. Most effective at lowering A1C. First choice for patients with A1C >8.5 or symptomatic hyperglycemia.
-Sulfonylurea. Least expensive oral agent.
-TZD. No hypoglycemia.
Step 3: If A1C > 7%, start or intensify insulin therapy.
-Adding or intensifying insulin is usually more effective than adding a third oral agent to reach glycemic goal.
-Intensify insulin usually with preprandial short or rapid-acting
insulin.
-With preprandial insulin secretagogues should be discontinued or
tapered.
Most patients will require more than one medication given the progressive nature of type 2 diabetes. Insulin and metformin or insulin and a TZD have greater synergy at lowering A1C than metformin and a TZD. In uncontrolled diabetics (fasting glucose >250, random glucose >300, A1C >10%, ketonuria, or symptoms) lifestyle interventions with insulin should be started first with addition of oral agents as symptoms resolve.
Goals of algorithm:
- Achieve and maintain glycemic goals.
- Initial therapy with lifestyle interventions and metformin.
- Rapid addition of medications.
- Early addition of insulin.
I believe that publication of this paper represents a historic event in diabetes care: only one English language set of guidelines (from Canadian Diabetes Association released in 2003 http://www.diabetes.ca/cpg2003/downloads/pharmacologic.pdf
) offered any suggestions on the order in which medication should be used. It is also an interesting document, in that various habitually antagonistic professional organizations (such as American Diabetes Association, American Association of Clinical Endocrinologists and European Association for the Study of Diabetes) all appear to largely support the recommendations of the paper. This idyllic harmony in the world of diabetology is so impressive, that I consider this paper to be a reflection of the new standard of care. In this regard I wish to emphasize the following:
1. This paper represents a wide consensus among experts in the field and, therefore, the standard of care. This is despite the fact that many points are not supported by high grade evidence.
2. As defined by ADA earlier, the new target goal of HbA1c in people with DMII is not defined as a pre-set number, but rather should be “as close to normal as possible”, but without “significant hypoglycemia”. This is a critical change. It follows that because insulin sensitizers (Metformin, TZDs, Exenatide and Vildagliptin) introduce a minimal risk of hypoglycemia, their doses should be aggressively maximized in patients with very reasonable, but still elevated HbA1c levels in the absence of contraindications. This is especially true for older meds (metformin and TZDs) with well described safety profile (I urge you all to exercise reasonable caution with any and all new pharmaceuticals, procedures and devices). For example, according to the paper, a patient on Metformin 2g daily with A1c of 6.5% should be started on a TZD (if edema and weight gain are not important considerations).
3. A treatment approach much more aggressive than that widely practiced today is advocated. It is not O.K. to increase metformin from 500 qd to 1g qd in a patient with A1C of 9% and have them follow-up in 3 months. At this point it is less important what you do (which specific meds you use), than how aggressively you do it.
4. At least in certain circumstances, insulin use is recommended early. This is also a critical change in the paradigm, as most docs still reserve insulin for the time when oral meds fail. Again, a patient with A1c of 10% gets insulin upfront (with the sensitizers). In my personal experience the greatest obstacle to insulin lays with physicians, assuming that quality of life sacrifice and suffering from the injections are unacceptable to the patients. This observation is not unique to our institution and is supported by the literature. Again, in my practice, a “stick” with a 31 gauge 5mm pen needle is reported as being as painful as a mosquito bite (or even less) by even needle-phobic patients.
5. It is important to realize that there is not, and cannot be, data available concerning newer meds, which would robust enough for a consensus. Besides, cost is a limiting factor in many circumstances. That said, and referring to my call for curbing one’s enthusiasm about new technologies, I myself am rapidly moving towards using Exenatide as a second line agent (after Metformin) in obese patients, who can afford the medication.
barren ben
Good information about barren ben.
Researchers estimate that about 10 percent of Americans will develop diabetes during their lifetime and about twice that number will develop a milder form of diabetes called impaired glucose tolerance, or pre-diabetes. Diabetes and pre-diabetes often do not present any symptoms until a complication arises, making the disease difficult for patients to detect.
fudu
ghusa article