Clinical Briefs in Primary Care
Clinical Briefs in Primary Care
Insulin Plus Metformin vs Triple Oral Therapy in Type 2 Diabetes
Source: Schwartz S, et al. Diabetes Care. 2003;26:2238-2243.
Patient preferences often direct the use of multiple oral agents in an attempt to control DM2, in an effort to avoid using insulin. Trial data to date have not provided specific guidance about which agent(s) should be preferred to achieve glucose control. The UKPDS trial has indicated that sulfonylurea, metformin, and insulin are all effective tools to control glucose and reduce microvascular end points. Which combination of agents might provide the best outcomes remains indeterminate.
This 6-month study (n = 188) compared different treatment avenues after dual oral therapy no longer was effective in controlling glucose in DM2: adding a third oral agent, or switching to an insulin + metformin combination to achieve an A1C < 7%, using maximal doses of oral agents or insulin.
Insulin was administered as a 70/30 mix twice daily (two-thirds of the total daily dose in the morning). The oral agents were insulin secretagogues, thiazolidinediones, and metformin. Baseline A1C was approximately 9.6 in both groups.
Although there was a statistically significant difference in A1C favoring the insulin group in the initial few weeks of the trial, by the close of the trial, there was no statistically significant difference (final A1C, 7.66-7.70). Lipid changes (LDL and triglycerides) were significantly more favorable in the insulin/metformin group, as was the daily cost of therapy ($3.20 vs $10.20). Severe hypoglycemia occurred in only 1 patient (in the insulin group). Despite an aggressive dose-escalation protocol, only one-third of patients in either group achieved the goal of A1C < 7%. Though insulin-based treatment was less costly, successful control was achieved equally well with either regimen.
ARB and ACE-I in Diabetic Nephropathy
Source: Rossing K, et al. Diabetes Care. 2003;26:2268-2274.
It has been consistently demonstrated that treatment of albuminuria in diabetics with either an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) produces reductions in albuminuria, delay in decline of renal function, and improvements in survival. Data on combination therapies (eg, ACE + spironolactone, ACE + ARB) is only beginning to accrue. This randomized crossover trial compared albuminuria in diabetic patients treated with maximal daily doses of ACEI alone (enalapril 40 mg, lisinopril 40 mg, or captopril 150 mg) vs maximal ACEI plus ARB (candesartan 16 mg/d) for 8 weeks in 20 diabetic men and women.
Adding ARB to ACEI resulted in a statistically significant reduction in albuminuria by 28% when compared with ACEI treatment alone. There was no correlation between other variables such as age, BMI, degree of albuminuria, plasma renin, cholesterol, ambulatory blood pressure, or salt intake. Even in as brief a period of time as 8 weeks, combination blockade of the renin-angiotensin-aldosterone system with ACEI + ARB provided superior renoprotection to ACEI alone.
Low-Glycemic Index Diets and Diabetes
Source: Brand-Miller J, et al. Diabetes Care. 2003;26;2261-2267.
The effect of lifestyle modulation in diabetes is sometimes overshadowed by the favorable effect of pharmacotherapy, despite the data indicating for instance that diet and exercise are more efficacious in prevention of diabetes than medication. Glycemic index is a measurement of the glycemic effect of a food, recognizing that 2 foods with the same overall amount of carbohydrate may have as much as a 5-fold difference in glucose level achieved. Observational data have suggested that it is the glycemic index of carbohydrate, rather than the total amount, that is associated with both development of diabetes and cardiovascular consequences. Unfortunately, prospective trials of low glycemic index foods have produced conflicting results. Major consensus groups differ on whether low glycemic index foods should be preferred.
This meta-analysis reviewed 14 randomized controlled trials (356 subjects) ranging in duration from 2 weeks to 1 year. A low glycemic index diet provided a statistically significant 0.4 lower A1C than "conventional" diet; similarly, fructosamine (a marker of mean glucose exposure over a 2-3 week period, as opposed to the 3 months exposure for A1C) was more favorable in the low glycemic index group. These data suggest that if clinicians were to use a low glycemic index diet in their diabetic patients, within 10 weeks time the patient might enjoy as much as a 0.4 improvement in A1C.
Ultralow-Dose Estrogen and Bone in Older Women
Source: Prestwood KM, et al. JAMA. 2003;290:1042-1048.
Hormone replacement therapy (HRT), has been found to have favorable effects upon osteoporosis and fracture risk in postmenopausal women. Unfortunately, this bone benefit is at the expense of increased risk for breast cancer, heart disease, stroke, and DVT. The increased risks are generally acknowledged to outweigh benefits for most women, though the jury is still out on estrogen replacement (ERT) without progesterone (in hysterectomized women).
In an effort to reduce risk, decrements in estrogen dose have been evaluated, usually in combination with supplements of calcium and vitamin D. This randomized, double-blind placebo controlled trial evaluated the provision of 0.25 mg/d of 17-beta estradiol (17-ERT), which is one-fourth to one-half the "conventional" dose previously used, daily for 4 years. End points included bone mineral density (BMD) and markers of bone turnover. Women were all menopausal, and in those women who had not undergone hysterectomy, 100 mg/d micronized progesterone was given for 2 weeks every 6 months. All study subjects were given supplemental vitamin D (1000 IU/d) and calcium (1300 mg/d).
In participants who received this low-dose estrogen, BMD by DEXA scanning showed favorable effects at the femoral neck, hip, spine, and total body. Bone turnover markers were also favorably affected.
At this low dose, the adverse effect profile was essentially indistinguishable from placebo, including breast tenderness. It is encouraging to note that ultra-low-dose estrogen has favorable bone effects. Ultimately, it will be essential to ascertain whether the BMD changes found will be reflected in fracture risk reduction. Additionally, though lower estrogen dose might be anticipated to reduce risk of serious adverse events, this remains to be determined.
Effect of Intensity of Oral Anticoagulation in Atrial Fibrillation
Source: Hylek EM, et al. N Engl J Med. 2003;349:1019-1026.
The value of warfarin antico-agulation (WAC) in atrial fibrillation (AF) to prevent ischemic stroke is well established. Despite therapeutic levels of WAC, however, some AF patients still suffer ischemic stroke. In persons who do suffer stroke while on WAC, it is unclear whether their stroke severity is related to degree of anticoagulation. To clarify that question, this investigation studied acute ischemic stroke (n = 596) among persons with nonvalvular AF who were being treated at the time of stroke with WAC (32%), aspirin (27%), or were on no prophylactic treatment. In patients on WAC, stroke severity was assessed in relation to INR, comparing those with an INR > 2 to patients having an INR < 2.
For the end point of mortality or discharge with severe stroke, there was a dramatic disadvantage demonstrated for stroke patients with an INR < 2 (15% vs 5%). The relative hazard for death within 30 days for patients with an INR < 2 was increased over 3-fold.
Stroke that occurs while on WAC in AF is less severe, and has more favorable mortality outcome, when the INR is maintained at a level of > 2. Since increased risk of intracranial hemorrhage was not seen until INR levels rose to > 3.9, maintenance of the traditionally accepted INR 2-3 range appears to maximize benefit, and minimize risk. n
Patient Knowledge and Awareness of Hypertension
Source: Alexander M, et al. J Clin Hypertens. 2003;5:254-260.
Despite a diversity of excellent pharmacotherapeutic tools for treating hypertension (HTN), national population surveys continue to indicate that there is much room for improvement in HTN detection, awareness, and control. Of course, if patients are unaware of BP goals, or their own BP and its adequacy of control, there is substantially less likelihood that they will achieve all the potential benefits of antihypertensive treatment.
Based upon a recent survey of hypertensive patients in the Northern California Kaiser Permanente Medical Care system (n = 2500), there remains a great deal of room for improvement in patients’ knowledge about blood pressure. Among this population, almost 80% of persons with BP > 140/90 did not recognize their BP as "high," although 38.5% identified this level of BP as "borderline high;" a similar number of individuals were not able to recall their BP levels taken at the most recent clinic visit. Perhaps most distressing is that the majority of patients neither knew a goal for their BP treatment, nor was able to appropriately identify whether systolic or diastolic BP levels were a greater risk factor.
Encouragingly, more than 85% of patients recognized that HTN increased risk for stroke and MI, but only half as many individuals knew that HTN might increase risk of kidney disease. The message that patients need to know their BP, BP goals, and the greater relative risk of elevated systolic than diastolic blood pressure will have to be given greater attention by clinicians and other patient educators.
Insulin Plus Metformin vs Triple Oral Therapy in Type 2 Diabetes; ARB and ACE-I in Diabetic Nephropathy; Low-Glycemic Index Diets and Diabetes; Ultralow-Dose Estrogen and Bone in Older Women; Effect of Intensity of Oral Anticoagulation in Atrial Fibrillation; Patient Knowledge and Awareness of HypertensionSubscribe Now for Access
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