Abstract & Commentary
Synopsis: Glipizide and repaglinide are both effective in lowering the postprandial blood glucose.
Source: Cozma LS, et al. Diabetes Care. 2002;25:1271-1276.
Cozma and colleagues note that "recent prospective studies have attempted to assess the effects of fasting and postprandial hyperglycemia independent of each other." There is increasing evidence that postprandial glucose levels may contribute more to diabetic complications than fasting levels of glucose.
Cozma et al, therefore, attempted to compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single 500-kcal test meal.
Twelve type 2 diabetics with early diabetes (A1c of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received placebo, 2 mg repaglinide, 5 mg glipizide, and 5 mg glibenclamide in a random fashion during the trial. Administration of each drug was followed by a single standard 500-kcal test meal.
All 3 drugs were equally effective on the total prandial insulin secretion. However, clear differences were noted in the early insulin secretion; both repaglinide and glipizide increased secretion in nondiabetic subjects by 61% and 34%, respectively, compared with placebo. In diabetic patients, the difference compared to placebo was 37% and 47%, respectively. The difference between glipizide and glibenclamide reached significance in both groups; whereas repaglinide was more effective only in nondiabetics. All 3 drugs were effective in decreasing total glucose in both diabetics and nondiabetics. In the nondiabetic subjects, however, repaglinide was significantly more effective than glibenclamide. The differences disappeared in the diabetic subjects, probably as a result of increased prevalence of insulin resistance in this group.
Repaglinide and glipizide—but not glibenclamide—significantly enhanced the early insulin secretion in both diabetic and nondiabetic subjects with preserved beta cell function after a single meal.
Comment by Ralph R. Hall, MD, FACP
Another way to state the purpose of this study is: How do the 3 insulinotropic agents used in this study effect the early and late phases of insulin release from the pancreas and how might this effect the postprandial blood glucose level? The importance of the postprandial blood glucose is that it seems to be more closely correlated with arteriosclerotic vascular disease than fasting blood glucose levels,1 and that the nonfasting blood glucose level is a better marker for diabetic control than the fasting glucose level.2
We now have a variety of new insulins and insulinotropic agents to use and it is important to know which one will get the results we desire. However, a question raised by the accompanying editorial is are they worth the extra costs compared with the earlier agents?3 You and your patient will be the best judges of this question.
As the Cohen and Ramlo-Halsted note, large randomized trials "have shown approximate equivalence for the efficacy between repaglinide and sulfonylureas and slightly lower efficacy for nateglinide in terms of A1c lowering."3 To make the best informed decisions about which drug to use, we need to do a better job of stratifying our patients in terms of the stage of their type 2 diabetes and perhaps move to insulin therapy earlier in the course of the disease. We still have to realize that there are no data that prove tight control will reduce the incidence of macrovascular disease.4 However, there is strong evidence for lowering the A1c to prevent microvascular complications.
If any of these therapies worked as well as weight loss and exercise and for so little cost, there would be large headlines extolling their virtues in The Wall Street Journal!
Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
References
1. Shaw JE, et al. Diabetologia. 1999;42:1050-1054.
2. Avignon A, et al. Diabetes Care. 1997;20:1822-1826.
3. Cohen RM, Ramlo-Halsted BA. Diabetes Care. 2002; 25:1472-1473.
4. UK Prospective Diabetes Study Group (UKPDS 33). Lancet. 1998;352:837-853
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