Intensive Blood glucose control with sulphonylureas or insulin decreases the ris
Intensive Blood glucose control with sulphonylureas or insulin decreases the risk of microvascular but not macrovascular disease
Abstract & Commentary
Synopsis: Intense blood glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications but not macrovascular outcomes. Intensive treatment increased the risk of hypoglycemia.
Source: UK Prospective Diabetes Study (UKPDS 34) Group. Lancet 1998;352:837-839.
This study has been widely anticipated since it is a large, carefully controlled study. It was designed to establish whether, in patients with type 2 diabetes, intensive blood glucose control reduced the risk of macrovascular or microvascular complications and whether any particular therapy was advantageous. In the United Kingdom, 9% of the patients with type 2 diabetes develop microvascular complications while 59% of the deaths are due to macrovascular disease.
Three thousand eight hundred seven newly diagnosed patients (median age, 54 years) who, after three months of diet treatment, had a mean of two fasting plasma glucose (FPG) concentrations of 110-270 mg/dL were randomly assigned intensive policy with a sulphonylureas or with insulin or conventional treatment with diet. The aim of the intensive group was a FPG less than 108 mg/dL. In the conventional group, the aim was the best FPG achievable with diet alone. The end points were any diabetes-related end point (sudden death, death from hyper or hypoglycemia, renal failure, amputation, vetreous hemorrhages, retinopathy with photocoagulation, or other diabetes related death).
Over 10 years, the HbA1C averaged 7% in the intensive group compared with 7.9% in the conventional group. There was no difference in the HbA1C among the agents in the intensive group. Weight gain was significantly higher in the intensive group (mean, 2.9 kg). Those treated with insulin had average weight gains of 4 kg.
Compared with the conventional group, the risk in the intensive group was 12% lower for any diabetes-related end point; 10% lower for diabetes-related death; and 6% lower for all-cause mortality. These complications were related to the reduction in microvascular disease only.
Intense blood glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications but not macrovascular outcomes. Intensive treatment increased the risk of hypoglycemia.
Comment by Ralph R. Hall, MD, FACP
These findings in the UKPDS were presented with three additional portions of the study in The Lancet and the British Medical Journal in September 1998.1-4
Perhaps the most important finding in UKPDS(33) was that there was a marked reduction in the progression of renal disease. There was a 67% risk reduction in this group who began the study with a two-fold increase in their serum creatinine. An interesting and controversial aspect of the UKPDS(34) was a study that involved intensive therapy with metformin alone in obese type 2 patients.2 This group of patients had a 32% reduction in diabetes-related end points, 42% reduction for diabetes-related death, and 36% for all-cause mortality. The risk reduction in this group of patients was related to both macrovascular and microvascular disease.
Controversy has developed, however, because in another group of patients when metformin was added early in the study period to patients receiving sulfonylureas, the morbidity and mortality was actually increased. David Nathan5 in an editorial in The Lancet thought that the latter finding negated the favorable findings with metformin alone. There was the concern by both Nathan and spokespersons for the American Diabetes Society that these findings should be disregarded until further studies support the UKPDS studies.
My perspective regarding these findings is that until further studies are available, I will use therapy with metformin as the only drug when possible and will avoid combining it with sulfonylureas. Rather, when combinations are needed, I will use insulin and troglitizone.
The rational for this approach is the favorable effects on lipoprotein quality, quantity, and vasodilation as compared to the sulfonylureas, which inhibits vasodilatory responses to ischemia and does not produce favorable effects on lipid levels or quality.6 The two UKPDS papers in the British Medical Journal showed that tight blood pressure control with atenolol or captopril decreased the risk of stroke by 44%, heart failure by 56%, and death from diabetes-related causes by 32%. As pointed out by others, there is no longer an excuse not to aim for tight glucose and blood pressure control in type 2 diabetes. This means more monitoring, more office visits, and better patient and physician education regarding the care of type 2 diabetics. Not only will the quality of life for these patients improve, but long-term costs of care will significantly decrease.
References
1. UKPDS(33). Lancet 1998;352:830-845.
2. UKPDS(34). Lancet 1998;352:854-859.
3. UKPDS(38). BMJ 1998;317:703-713.
4. UKPDS(39). BMJ 1998;317:713-720.
5. Nathan D. Lancet 1998;352:832-833.
6. Hsueh WA, Law RE. J Investig Med 1998;46:387-390.
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