By Louis Kuritzky, MD
Insulin 70/30 Mix Plus Metformin vs Triple Oral Therapy in Type 2 Diabetes
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.
Schwartz S, et al. Diabetes Care. 2003;26:2238-2243.
ARB and ACE-I in Diabetic Nephropathy
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 brief a period of time as 8 weeks, combination blockade of the reninangiotensin-aldosterone system with ACEI + ARB provided superior renoprotection to ACEI alone.
Rossing K, et al. Diabetes Care. 2003;26:2268-2274.
Low-Glycemic Index Diets and Diabetes
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.
Brand-Miller J, et al. Diabetes Care. 2003;26:2261-2267.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.