Insulin And Oral Hypoglycemic Agents

Intensive blood glucose control has, in large intervention trials, been shown to increase body weight in both type 1 and type 2 diabetic patients (82,83). In the Diabetes Control and Complications Trial (DCCT), intensive treatment with either multiple daily injections of insulin or continuous subcutaneous insulin infusion resulted in a 60% increased risk of a body weight more than 120% of the ideal body weight. On average, the intensively treated patients had a weight gain of 5 kg compared to the patients treated with conventional insulin regimens (82). Most of the weight changes appeared during the first year of treatment (82,84). In another DCCT substudy it was concluded that the changes in lipid levels and blood pressure that occur with excessive weight gain with intensive therapy were similar to those seen in the insulin resistance syndrome and may increase the risk of coronary artery disease in this subset of subjects with time (85). Not surprisingly, more female than male patients have been found to be worried about weight gain as a side effect and this may prove a significant impediment to the clinical implementation of intensive insulin treatments. It has been estimated that 70% of the weight gain can be accounted for by reduced glucosuria and that 30% is due to a reduction in energy expenditure by the reversal of the catabolic changes in carbohydrate, protein and lipid metabolism (86). Increased body weight has also been found in young type 1 patients on intensive therapy and might, especially in adolescent girls, influence adherence to good metabolic control regimens. (87,88).

In type 2 diabetes, the UKPDS study showed that weight gain was significantly higher in the intensive group (mean 5.4 kg) than in the conventional group (2.5 kg), and patients assigned to insulin had a greater gain in weight (6.5 kg) than those assigned to chlorpropamide (5.1 kg) or glibenclam-ide (3.2 kg) (83).

In contrast to these findings, a UKPDS substudy with metformin in obese type 2 patients showed that the weight gain in metformin treated patients was similar to the conventional control group and less than the weight increases found in patients assigned to intensive treatment with insulin or sul-phonylureas (89). In addition, patients who received metformin also had a more favorable outcome with respect to diabetes complications and mortality (89). If diabetes control cannot be achieved by metformin treatment alone, it should be combined with bedtime insulin since this treatment modality has been shown in a recent 12-month study to prevent weight gain and provide acceptable metabolic regulation (90). Also the newer glitazones have been associated with a modest, but significant, weight gain, although long-term data are still lacking.

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